WO2015112915A1 - Endoprothèses biodégradables et leurs procédés de fabrication - Google Patents

Endoprothèses biodégradables et leurs procédés de fabrication Download PDF

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Publication number
WO2015112915A1
WO2015112915A1 PCT/US2015/012780 US2015012780W WO2015112915A1 WO 2015112915 A1 WO2015112915 A1 WO 2015112915A1 US 2015012780 W US2015012780 W US 2015012780W WO 2015112915 A1 WO2015112915 A1 WO 2015112915A1
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WIPO (PCT)
Prior art keywords
stent
diameter
polymer
polymeric
biodegradable
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Application number
PCT/US2015/012780
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English (en)
Inventor
Xiaoxia Zheng
John Yan
Vinayak Bhat
Original Assignee
Elixir Medical Corporation
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Application filed by Elixir Medical Corporation filed Critical Elixir Medical Corporation
Publication of WO2015112915A1 publication Critical patent/WO2015112915A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
    • A61F2/91—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
    • A61F2/915—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/04—Macromolecular materials
    • A61L31/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
    • A61F2/91—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
    • A61F2/915—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other
    • A61F2002/91533—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other characterised by the phase between adjacent bands
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
    • A61F2/91—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
    • A61F2/915—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other
    • A61F2002/9155—Adjacent bands being connected to each other
    • A61F2002/91575—Adjacent bands being connected to each other connected peak to trough
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2210/00—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2210/0004—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof bioabsorbable

Definitions

  • the present invention relates generally to medical devices and methods for their fabrication.
  • the present invention relates to the fabrication of biodegradable endoprostheses, such as stents, having enhanced strength and controlled persistence after implantation.
  • Stents are generally tubular- shaped devices which function to hold open or reinforce a segment of a blood vessel or other body lumen, such as a coronary artery, carotid artery, saphenous vein graft, or femoral artery. They also are suitable to support and hold back a dissected arterial lining that could occlude the body lumen, to stabilize plaque, or to support bioprosthetic valves. Stents can be formed from various materials, particularly polymeric and/or metallic materials, and may be non-degradable, biodegradable, or be formed from both degradable and non-degradable components. Stents are typically delivered to the target area within the body lumen using a catheter.
  • the stent With balloon-expandable stents, the stent is mounted to a balloon catheter, navigated to the appropriate area, and the stent is expanded by inflating the balloon. A self-expanding stent is delivered to the target area and released, expanding to the required diameter to treat the disease. Stents may also elute various drugs and
  • biodegradable stents and other endoprostheses are usually formed from polymers which degrade by hydrolysis and other reaction mechanisms in the vascular or other luminal environment over time.
  • Peripheral stents for treatment of lesions in the superficial femoral artery, the infrapopliteal artery, femoropopliteal artery, iliac arteries or in other above the knee or below the knee indications are commonly self-expading stents such as those made of Nitnol.
  • Nitnol and other self-expanding stents have better recovery after crushing from an external force than balloon expandable stents and are therefore considered more suitable for lesions in the peripheral vessels.
  • Biodegradable implantable devices and methods of making them are also described in commonly owned U.S. Provisional Patent Application No. 60/668,707, filed on April 5, 2005; U.S. Provisional Patent Application No. 60/885,700, filed on January 19, 2007; U.S. Patent Application No. 11/398,363, filed on April 4, 2006; U.S. Patent Application No. 12/016,077, filed on January 17, 2008; and U.S. Patent Application No. 12/016,085, filed on January 17, 2008, the entire disclosure of each of which is incorporated herein by reference.
  • a biodegradable stent prosthesis in one aspect of the invention, includes a tubular body comprising a biodegradable polymeric material, wherein the tubular body is expandable from a crimped configuration to an expanded configuration and has a radial strength of greater than or equal to 3.0 psi and a conformability of less than 0.025 N/mm.
  • a biodegradable stent prosthesis in another aspect of the invention, includes a tubular body comprising a biodegradable polymeric material, wherein the tubular body is expandable from a crimped configuration to an expanded configuration and has a radial strength of greater than or equal to 3.0 psi and wherein a force to compress the stent by 5% of its length is less than 0.4 N.
  • the stent prostheses may be formed from one or more amorphous, semi-crystalline, or crystalline biodegradable polymers.
  • amorphous polymers is preferable in some cases since they can provide relatively short periods of biodegradation, usually less than two years, often less than one year, frequently less than nine months, and sometimes shorter than six months, or even shorter.
  • the polymers are modified or treated to introduce a desired degree of crystallinity.
  • introducing crystallinity into the polymer increases the strength of the polymer so that it is suitable for use as an endoprosthesis and in some cases without substantially lengthening the period of biodegradation after implantation.
  • the polymeric material is treated to achieve a desired degree of crystallinity.
  • the polymeric material is treated to control crystallinity.
  • treatment comprises a heat treatment of the polymeric material or the tubular body preferably at an initial diameter to a temperature above its glass transition temperature of the polymeric material and below its melting point for a period ranging from a fraction of a second to 7 days.
  • Initial diameter is the diameter of the polymeric material or the tubular body as-formed, or the diameter before patterning, or the diameter after patterning, or the diameter before crimping.
  • the polymeric material or the tubular body in one example may be cooled after heating to a temperature ranging from below ambient temperature to ambient or above temperature over a period ranging from a fraction of a second to 7 days.
  • the tubular body or polymeric material initial diameter is approximately 1-1.5 times the stent deployment diameter.
  • the tubular body is treated at diameter below initial diameter, or between initial diameter and crimped diameter.
  • the treatment comprises heating the tubular body to a temperature about or below Tg for a period ranging from a fraction of a second to 7 days.
  • the heat treatment at the below initial diameter comprises heat treatment about or above Tg and below Tm for a period ranging from a fraction of a second to 5 hours, or preferably less than 2 hour, or more preferably less than 60 minutes, or most preferably less than 15 minutes.
  • the polymeric material or the tubular body after forming is treated comprising heat at temperature about or less than Tg.
  • the tubular body after forming and excluding patterning is treated comprising heat at temperature about or less than Tg. Durations are similar to above ranges. Other suitable temperatures and times are described herein.
  • the initial diameter is 0.9-1.5 times the stent deployment diameter, or the stent nominal diameter.
  • the stent nominal diameter is the labeled deployment stent diameter.
  • the stent deployment diameter usually is the deployed diameter of the stent at nominal or bigger diameter.
  • the initial diameter is smaller than the deployed stent diameter or smaller than the labeled stent deployed diameter.
  • the stent prosthesis after deployment from a crimped
  • the stent prosthesis after deployment from a crimped configuration to an expanded diameter in physiologic environment further expands to a larger diameter.
  • the stent prosthesis after deployment from a crimped configuration to an expanded diameter in physiologic environment further expands to a larger diameter by at least 0.05mm within 20 minutes.
  • the stent prosthesis after deployment from a crimped configuration to an expanded diameter in physiologic environment further expands to a larger diameter by at least 0.1 mm within 20 minutes.
  • the stent prosthesis after deployment from a crimped configuration to an expanded diameter in physiologic environment further expands to a larger diameter substantially apposing the body lumen.
  • the stent prosthesis after deployment from a crimped configuration to an expanded diameter in physiologic environment further expands to a larger diameter substantially apposing the body lumen within 9 months.
  • the optional heat treatment of the one or more biodegradable polymeric materials, or the tubular body, the stent material, or the stent may occur at a temperature below T g , or at about T g , or at greater than T g of the one or more biodegradable polymeric materials.
  • the optional heating may take place at a temperature within 2°C, or within 4°C, or within 6°C, or within 8°C, or within 10°C, or within 12°C, or within 14°C, or within 16°C, or within 18°C, or within 20°C of T g of the one or more biodegradable polymeric materials (where "within" may be above or below the T g ).
  • the optional treating may take place for at least about 1 x 10 " 12 seconds (s), or at least about 1 x 10 "9 s, or at least about 1 x 10 "6 s, or at least about 1 x 10 "3 s, or at least about 1 x 10 " s, or at least about 0.1 s, or at least about 1 s, or at least about 10 s, or at least about 1 minute (min), or at least about 10 min, or at least about 1 hour (h) or at least about 10 h, or at least about 1 day, or at least about 5 days, or at least about 10 days, or at least about 1 month, or at least about 2 months, or at least about 3 months, or at least about 4 months, or at least about 5 months, or at least about 6 months, or at least about 1 year.
  • the treating, such as heating may take place for about 1 min to about 10 min, or about 3 min to about 10 min, or about 5 min to about 10 min, or about 3 min to
  • the polymers' crystallinity after modification or treatment is increased by at least 10% of the original crystallinity of the polymer material, preferably by at least 20% of the original crystallinity of the polymer material, preferably by at least 50% of the original crystallinity of the polymer material, and more preferably by at least 100 % of the original crystallinity of the polymer material.
  • the crystallinity of the polymeric material after modification is decreased by at least 10% of the original crystallinity of the polymer material before modification, preferably by at least 20% of the original crystallinity of the polymer material, preferably by at least 50% of the original crystallinity of the polymer material, and more preferably by at least 100% of the original crystallinity of the polymer material, and more preferably by at least 1000% of the original crystallinity of the polymer material.
  • treatment or modification of the polymeric material has crystallinity that is substantially the same after treatment and before treatment of the polymeric material.
  • polymer materials will have a crystallinity in the range from 10% to 20% after modification as described herein below. In yet other preferred embodiments, polymer materials will have a crystallinity in the range from 1 to 10%, or 10% to 30% after modification. In yet other preferred embodiments, polymer materials will have a crystallinity between 1% and 35% after modification. In yet other preferred embodiments, polymer materials will have a crystallinity between 1% and 40% after modification.
  • crystallinity refers to a degree of structural order or perfection within a polymer matrix as known to someone skilled in the art and methods to measure crystallinity as well such as differential scanning calorimetry.
  • the one or more materials comprising the body, or the stent, or the tubular body may have a controlled crystallinity.
  • the crystallinity is less than 50%, or less than 40%, or less than 35%, or less than 30%, or less than 25%, or less than 20%, or less than 15%, or less than 10%, or less than 5%.
  • the one or more materials comprising the body, or the stent, or the tubular body, or the polymeric material may have a crystallinity of about 0% or greater than 0%, or greater than 5%, or greater than 10%, or greater than about 15%, or greater than about 20%, or greater than about 25%, or greater than about 30%, or greater than about 35%, or greater than 40%, or greater than 50%.
  • the one or more materials comprising the body, or the stent, or the tubular body may have a crystallinity of about 0% to less than 60%, or about 0 to less than 55%, or about 0 to less than 50%, or about 0 to less than 40%, or about 0% to less than 35%, or about 0% to less than 30%, or about 0% to less than 25%, or about 0% to less than 20%, or about 0% to less than 15%, or about 0% to less than 10%, or about 0% to less than 5%.
  • the one or more materials comprising the body, or the stent, or the tubular body or polymeric material may have a crystallinity of about 5% to about 60%, or about 5% to about 55%, or about 5% to about 50%, or about 5% to about 40%, or about 5% to about 45%, or about 5% to about 30%, or about 10% to about 25%, or about 15% to about 20%.
  • the polymer or polymeric material after treatment is amorphous, in other embodiments the polymer or polymeric material after treatment is semi- crystalline, yet in other embodiments the polymer or polymeric material after treatment is crystalline.
  • the polymeric material prior to a treatment is amorphous.
  • the polymeric material prior to a treatment is semi- crystalline.
  • the polymeric material prior to a treatment is crystalline.
  • Crystallinity can be measured by differential scanning calorimetry (Reading, M. et al, Measurement of crystallinity in polymers using modulated temperature differential scanning calorimetry, in Material Characterization by Dynamic and Modulated Thermal Analytical Techniques, ASTM STP 1402, Riga, A.T. et al. Ed, (2001) pp. 17-31.
  • methods for fabricating biodegradable prostheses comprise providing a tubular body having an initial diameter as-formed, or before patterning, or after patterning, where the tubular body comprises a biodegradable polymeric material.
  • the polymeric material comprises one or more polymers, or one or more co-polymers, or a combination thereof.
  • the polymeric material comprises one or more polymers, or one or more co-polymers, or one or more monomers, or a combination thereof.
  • the polymeric material or the tubular body is treated to control crystallinity preferably to between 1% and 50%, or more preferably to between 1% and 35%.
  • the polymeric material or the tubular body treatment comprises a heat treatment preferably at substantially the initial diameter, preferably when the initial diameter is 1-1.5 times the stent deployment diameter, to a temperature above glass transition temperature of the polymeric material and below its melting point for a period ranging from a fraction of a second to 7 days.
  • the polymeric material or the tubular body in one embodiment may be cooled after heating to a temperature ranging from below ambient temperature to ambient or above temperature over a period ranging from a fraction of a second to 7 days.
  • the polymeric material or the tubular body initial diameter is approximately 1-1.5 times the stent deployment diameter or stent nominal deployment diameter, or stent labeled deployment diameter.
  • the initial diameter is approximately 0.9-1.5 times the stent deployment diameter or stent nominal deployment diameter, or stent labeled deployment diameter. In another embodiment, the initial diameter is smaller than the stent deployment diameter or stent nominal deployment diameter, or stent labeled deployment diameter.
  • the stent deployment diameter in a preferred embodiment is typically the diameter of the stent deployed to approximately nominal or labeled stent diameter but can also be the deployed diameter above the stent nominal or labeled diameter.
  • Stent nominal deployed diameter can be accomplished in one example by inflating the deploying balloon to nominal or labeled diameter to deploy the stent to nominal or labeled diameter.
  • the polymeric material or the tubular body is patterned at substantially the initial diameter and is crimped subsequently to a crimped diameter that is smaller than the initial diameter.
  • the polymeric material or the tubular body is treated at diameter between initial diameter and crimped diameter.
  • the treatment comprises heating the tubular body to a temperature about or below Tg for a period ranging from a fraction of a second to 7 days.
  • the heat treatment at the below initial diameter comprises heat treatment about or above Tg and below Tm for a period ranging from a fraction of a second to 5 hours, or preferably less than 2 hour, or most preferably less than 60 minutes, or most preferably less than 15 minutes.
  • the patterned stent in one embodiment is crimped in one or more steps and fitted onto a delivery system or crimped onto the delivery system at a diameter that is less than the initial diameter.
  • the crimped diameter is less than 3mm, in another embodiment, the crimped diameter is less than 2.5mm, in another embodiment, the crimped diameter is less than 2.0mm in a third embodiment, the crimped diameter is less than 1.5mm, in a fourth embodiment, the crimped diameter is less than 1mm, in a fifth embodiment, the crimped diameter is less than 0.8mm.
  • the stent is capable to expand from the crimped diameter to a deployed diameter preferably at about body temperature (in water or dry) and have sufficient strength to support a body lumen.
  • the stent is capable to expand from the crimped diameter to a deployed diameter at about body temperature (in aqueous or water or dry) without fracture and have sufficient strength to support a body lumen.
  • the stent is capable to crimp from an expanded diameter, wherein the expanded diameter is larger than the crimped diameter, and expand from the crimped diameter to a deployed diameter at about body temperature (in aqueous or water or dry) without fracture and have sufficient strength to support a body lumen.
  • sufficient radial strength to support a body lumen is maintained for at least 1 month, or for at least 2 months, for at least 3 months.
  • the diameter of the scaffold increases after expansion to nominal diameter or between nominal and 1.1 times nominal diameter by 0.1mm to 0.5mm between 5 minutes after deployment to an expanded diameter and 1 hour. In other embodiments, the diameter of the scaffold did not substantially decrease over time. In still other embodiments, the diameter of the scaffold did not substantially increase over time.
  • an expandable stent comprising a biodegradable polymeric material having an initial configuration is provided.
  • the expandable stent at body
  • the temperature can be self-expandable from a crimped configuration and further expandable to a second larger configuration.
  • the polymeric material has been treated to control one or more of crystallinity, Tg, or molecular weight.
  • Tg ranges from about 20 °C to about 50 °C.
  • the second configuration is a deployed configuration.
  • the stent expands to the first and second configurations without fracture and has sufficient strength to support a body lumen.
  • the first expanded configuration has a transverse dimention of at least 0.35 times, or at least 0.45 times, or at least 0.55 times, or at least 0.55 times, or at least 0.7 times, or at least 0.8 times, or at least 1 times the transverse dimension of the initial configuration.
  • the stent expands to the first expanded configuration within a period of 24 hours, or 12 hours, or 4 hours, or 2 hours, or 1 hour, or 30 minutes, or 5 minutes or 30 seconds.
  • the stent is balloon expandable to the second expanded configuration without fracture and with sufficient strength to support a body lumen.
  • an expandable stent comprising a biodegradable polymeric material having an initial configuration is provided.
  • the expandable stent at body
  • thermoelectric temperature can be expandable from a crimped configuration to a first expanded
  • the polymeric material is treated to control one or more of crystallinity, Tg, or molecular weight.
  • the expandable stent comprises a substantially continuous tubular body.
  • the stent expands to the first configuration without fracture and has sufficient strength to support a body lumen.
  • the stent has a nominal expanded configuration with a transverse dimension and the first expanded configuration has a transverse dimension that is at least 1 times the transverse dimension of the transverse dimension of the nominal expanded configuration.
  • the first expanded configuration is a deployed configuration.
  • the stent has a nominal expanded configuration with a transverse dimension and the first expanded configuration has a transverse dimension that is 1 time, or 1.1 times, or 1.2 times, or 1.3 times, or 1.35 times, or 1.4 times, or 1.45 times, or 1.5 times the transverse dimension of the transverse dimension of the nominal expanded configuration.
  • Fabricating a biodegradable stent can be accomplished through a variety of ways.
  • the biodegradable stent is fabricated by forming a tubular body using extrusion, molding such as injection molding, dipping, spraying such as spraying a tube or mandrel, printing such as 3D printing.
  • the tubular body in a preferred embodiment is formed first and then patterned into a structure capable of radial expansion from a crimped configuration preferably at body temperature.
  • the tubular body in another preferred embodiment is formed first and then patterned into a structure capable of radial expansion from a crimped configuration preferably at body temperature and preferably without fracture.
  • the tubular body in another preferred embodiment is formed first and then patterned into a structure capable of being crimped from an expanded configuration to a crimped diameter (at temperature about Tg or less than Tg), and at body temperature capable to be expanded from the crimped configuration preferably without fracture.
  • the polymeric material is patterned first and then forms a tubular body/stent capable of radial expansion at body temperature and/or capable to be crimped preferably at temperature about Tg or less than Tg.
  • the biodegradable stent is fabricated from a sheet (such as a flat sheet) joined at ends (such as opposite ends) to form a tubular body capable of radial expansion preferably at body temperature and/or capable to be crimped preferably at temperature about Tg or less than Tg, and patterned before and/or after joining. Joining sheet ends can be accomplished by a variety of methods such as adhesive, ultrasound, welding, melting the ends, chemical means, or treatment such as heating.
  • the tubular body formed from a sheet can be further treated to control crystallinity and Tg as described in this patent application.
  • the tubular body formed form the sheet has an initial diameter, preferably 1-1.5 times the stent deployed diameter.
  • the biodegradable stent is fabricated from weaving or braiding polymeric material fibers into a tubular body structure capable of expansion at body temperature and/or capable to be crimped at temperature preferably about Tg or less than Tg.
  • the initial tubular configuration which is capable of radial expansion at body temperature and/or capable of being crimped from an expanded diameter preferably at temperature about Tg or less than Tg (in aqueous or dry environment) wherein the initial diameter is preferably 1-1.5 times the stent deployed diameter (or the stent nominal diameter, or the stent labeled diameter) and preferably treated at the initial tubular diameter, to achieve controlled crystallinity preferably between 0 and 45%, or more preferably between 0 and 35% and a Tg greater than 37°C and less than 50°C, or more preferably greater than 37°C and less than 45°C) and the stent is capable to expand from a crimped configuration to an expanded configuration/diameter at body temperature and has sufficient strength to support a body lumen, and preferably without fracture.
  • the stent is capable to be crimped (at temperature preferably about Tg or below Tg), and expand from a crimped configuration to an expanded configuration/diameter at body temperature and has sufficient strength to support a body lumen, and preferably without fracture.
  • the biodegradable stent is formed using injection molding wherein the polymeric material is loaded inside a mold and the mold is treated once or more to control crystallinity preferably to between 1% and 55% (preferably between 1% and 35%) and treated to control Tg preferably to greater than 37°C and less than 50°C (or in another preferred embodiment control Tg to greater than 20°C and less than 50°C), or as described within this patent application.
  • the formed patterned tube/stent has an initial diameter, preferably 1-1.5 times the stent deployed diameter, and the treatment can take place before, and/or during, and/or after the molding process and the stent capable to radially expand preferably at body temperature (dry or in aqueous environment).
  • the stent in another embodiment is capable to be expanded from a crimped configuration (which is smaller than the expanded diameter) to an expanded diameter at body temperature and have sufficient strength to support a body lumen, and preferably without fracture.
  • the stent in another embodiment is capable to be crimped from an expanded diameter to a crimped diameter (at temperature preferably about Tg or less than Tg), and expanded from the crimped
  • the biodegradable stent can be fabricated using printing such as 3-D printing wherein the polymeric material is loaded onto the printer and treated to form a patterned tubular body/structure/stent wherein it has an initial diameter, preferably 1-1.5 times the stent deployed diameter, and is treated to control crystallinity and Tg as described within this patent application, and the stent is capable to radially expand at body temperature.
  • the stent in another embodiment is capable to expand from a crimped configuration to an expanded diameter at body temperature and has sufficient strength to support a body lumen, and preferably without fracture.
  • the stent in another preferred embodiment is capable to be crimped from an expanded diameter to a crimped configuration (at temperature preferably about Tg or less than Tg), and expand from the crimped configuration to an expanded diameter at body temperature and has sufficient strength to support a body lumen, and preferably without fracture.
  • crimping the stent when crimping the stent is at temperature about Tg or less than Tg, crimping the stent can be accomplished at temperature above Tg or within 20°C above Tg.
  • treatment by heat typically ranges from below Tg to below Tm, in some other cases treatment of the polymeric material can be about Tm or above for example when the stent is formed by printing or injection molding.
  • a preferred formation process comprises forming a tube using spraying a polymer or polymeric material comprising one or more polymer, co-polymer-or monomer dissolved in at least one solvent onto a cylindrical mandrel or other structure when the stent prosthesis desired shape is non cylindrical such as oblong shape or other shapes.
  • a dimension of the stent may be referred to as "transverse dimension" instead of diameter.
  • additives such as strength-enhancing materials, drugs, or the like, may be dissolved in the solvent or other solvents together with the polymer or polymeric material so that the materials are integrally or monolithically formed with the endoprosthesis tube.
  • methods according to embodiments of the invention may rely on obtaining a pre-formed polymer tube from a supplier or other outside source.
  • the polymeric tubular body is usually formed as a substantially continuous cylinder free from holes or other discontinuities.
  • the tubular body has a foraminous wall.
  • the tubular body is formed from a continuous tube.
  • the tubular body comprises a plurality of fibers woven into an expanded diameter, preferably the initial tubular configuration with a diameter preferably of 1-1.5 times the stent deployed diameter and preferably treated at the initial tubular diameter.
  • the polymeric material or the tubular body or deployed stent typically has an outside or inner diameter in the range from 2 mm to 25 mm, preferably 3mm to 10mm, or 3.5mm to 10mm, and a thickness preferably in the range from 0.01 mm to 0.5 mm, and may be cut into lengths suitable for individual endoprostheses, typically in the range from 5 mm to 40 mm but can also range from 1mm to 150cm.
  • the tubular body may be patterned into a suitable endoprosthesis structure, typically by laser cutting or other conventional processes such as milling, chemical etching, stamping, photolithography, etc.
  • the stent prosthesis is formed by 3D printing which patterns the tubular body/stent as it is being formed and optionally treated to control crystallinity and Tg to facilitate a stent capable to radially expand at body temperature and support a body lumen and preferably without fracture.
  • the tubular body comprises a plurality of fibers woven into the initial tubular configuration with a diameter preferably of 1-1.5 times the stent deployed diameter and preferably treated at the initial tubular diameter.
  • the stent tubular body is formed from a sheet joined at opposite ends and patterned either before or after joining.
  • a biodegradable endoprosthesis (e.g., a stent) is formed from a polymeric tube, wherein the tube is a substantially continuous cylinder.
  • the substantially continuous cylinder may be substantially free from holes, gaps, voids or other discontinuities.
  • the tube may be
  • the tubular body may have an outside diameter in the range from about 2 mm to 10 mm, or about 3 mm to about 9 mm, or about 4 mm to about 8 mm, or about 5 mm to about 7 mm.
  • the tubular body may have a thickness in the range from 0.01 mm to 0.5 mm, or about 0.05 mm to about 0.4 mm, or about 0.1 mm to about 0.3 mm.
  • the tubular body or polymeric material, or the stent has an initial diameter.
  • the initial diameter is 1-1.5 times the stent deployed diameter.
  • the initial diameter is 0.9-1.5 times the stent deployed diameter.
  • the initial diameter is less than the stent deployed diameter.
  • the initial diameter can be the as-formed diameter, or the diameter before patterning, or the diameter after patterning, or the diameter before crimping.
  • an endoprosthesis e.g., a stent
  • a polymeric tube that has a (e.g., inner or outer) diameter substantially equal to or smaller than deployed (e.g., inner or outer) diameter of the endoprosthesis.
  • an endoprosthesis e.g., a stent
  • a polymeric tube that has a (e.g., inner or outer) diameter, either when the tube is formed or after the tube is radially expanded to a second larger diameter, larger than deployed (e.g., inner or outer) diameter of the endoprosthesis.
  • Patterning a stent from a polymeric tube having a (e.g., inner or outer) diameter larger than deployed (e.g., inner or outer) diameter of the stent can impart advantageous characteristics to the stent, such as reducing radially inward recoil of the stent after deployment and/or improved strength.
  • a stent is patterned from a polymeric tube having a (e.g., inner or outer) diameter about 0.85, 0.90, 1.0, 1.05 to about 1.5 times, or about 1.1 to about 1.5 times, or about 1.1 to about 1.3 times, or about 1.15 to about 1.25 times, smaller, same, or larger than an intended deployed (e.g., inner or outer) diameter of the stent.
  • the stent is patterned from a polymeric tube having a (e.g., inner or outer) diameter about 1.1 to about 1.3 times larger than an intended deployed (e.g., inner) diameter of the stent.
  • a stent having a deployed (e.g., inner or outer) diameter of about 2.5, 3 or 3.5 mm can be patterned from a tube having a (e.g., inner or outer) diameter of about 2.75, 3.3 or 3.85 mm (1.1 times larger), or about 3.25, 3.9 or 4.55 mm (1.3 times larger), or some other (e.g., inner or outer) diameter larger than the deployed (e.g., inner or outer) diameter of the stent.
  • the initial diameter of the formed tube is larger than the crimped diameter (e.g., crimped diameter on a delivery system) of the stent prosthesis wherein the tubular body is expanded to a second larger diameter than the initial diameter before patterning or before crimping to the crimped diameter; or wherein the tubular body remains substantially the same diameter before patterning or before crimping to a crimped diameter; or wherein the tubular body is crimped to a smaller diameter than the initial formed diameter before patterning or after patterning.
  • the crimped diameter e.g., crimped diameter on a delivery system
  • the initial diameter of the formed tube is smaller than the crimped diameter of the stent prosthesis wherein the tubular body is expanded to a second larger diameter than the initial diameter before patterning or before crimping; or wherein the tubular body remains substantially the same diameter before patterning or before crimping; or wherein the tubular body is crimped to a smaller diameter than the crimped diameter of the stent prosthesis before patterning or after patterning.
  • the initial diameter of the formed tubular body is greater than 0.015 inches, or greater than 0.050 inches, or greater than 0.092 inches, or greater than 0.120 inches, or greater than 0.150 inches, in the as-formed diameter, or before patterning diameter, or after patterning diameter, or before crimping diameter.
  • Stent prosthesis intended deployment diameter is the diameter of the labeled or nominal or higher of the delivery system or balloon catheter, or higher.
  • a stent prosthesis is crimped onto a balloon labeled 3.0 mm diameter (e.g., deployed nominal diameter)
  • the stent prosthesis' deployed diameter or intended deployment diameter is 3.0mm or higher.
  • self expandable stent crimped onto a delivery system is labeled a certain deployment diameter.
  • a stent prosthesis or tubular body or polymeric material has initial diameter (or initial transverse dimension), preferably 1-1.5 times deployed diameter (deployed transverse dimension) or deployed nominal diameter (e.g., deployed nominal transverse dimension), where in the initial diameter (or initial transverse dimension) is as-formed diameter (or transverse dimension), before patterning diameter (or transverse dimension), or after patterning diameter (or transverse dimension), or before crimping diameter (or transverse dimension), and wherein the initial diameter (or initial transverse dimension) is greater than crimped diameter (or crimped transverse dimension).
  • a stent or tubular body first self-expands by at least 0.35 of initial diameter or transverse dimension, and then expands to second larger diameter or transverse dimension, which may be the deployed diameter or transverse dimension, preferably by balloon expansion.
  • the stent or tubular body may expand to 1.0 times or more, or 1.1 times or more, or 1.2 times or more, or 1.3 times or more, or 1.4 times or more, or 1.5 times or more the deployed diameter or nominal diameter (or transverse dimension) at body temperature, without fracturing.
  • the stent or tubular body or polymeric material is crimped from an expanded diameter to a crimped configuration, and at body temperature expands to 1.0 times or more, or 1.1 times or more, or 1.2 times or more, or 1.3 times or more, or 1.4 times or more, or 1.5 times or more the deployed diameter or nominal diameter (or transverse dimension), without fracturing.
  • the stent or tubular body is crimped from an expanded diameter to a crimped configuration wherein the ratio of expanded diameter to crimped configuration is at least 1.5, and at body temperature the stent expands to 1.0 times or more, or 1.1 times or more, or 1.2 times or more, or 1.3 times or more, or 1.4 times or more, or 1.5 times or more the deployed diameter or nominal diameter (or transverse dimension), without fracturing.
  • the stent or tubular body is crimped from an expanded diameter to a crimped configuration wherein the ratio of expanded diameter to crimped configuration is at least 2, and at body temperature the stent expands to 1.0 times or more, or 1.1 times or more, or 1.2 times or more, or 1.3 times or more, or 1.4 times or more, or 1.5 times or more the deployed diameter or nominal diameter (or transverse dimension), without fracturing.
  • the stent or tubular body is crimped from an expanded diameter to a crimped configuration wherein the ratio of expanded diameter to crimped configuration is at least 2.5, and at body temperature the stent expands to 1.0 times or more, or 1.1 times or more, or 1.2 times or more, or 1.3 times or more, or 1.4 times or more, or 1.5 times or more the deployed diameter or nominal diameter (or transverse dimension), without fracturing.
  • the stent or tubular body is crimped from an expanded diameter to a crimped configuration wherein the ratio of expanded diameter to crimped configuration is at least 3, or at least 4, or at least 5, or at least 6, or at least 7, and at body temperature the stent expands to 1.0 times or more, or 1.1 times or more, or 1.2 times or more, or 1.3 times or more, or 1.4 times or more, or 1.5 times or more the deployed diameter or nominal diameter (or transverse dimension), without fracturing.
  • the stent or tubular body is crimped from an expanded diameter to a crimped configuration wherein the ratio of expanded diameter to crimped configuration is at least 2, or at least 2.5, or at least 3, or at least 3.5, or at least 4, wherein the stent at body temperature is expandable from the crimped configuration to the deployed configuration without fracture, wherein the deployed configuration is the nominal or higher deployment diameter.
  • the stent is balloon expanded to its deployed diameter (or transverse dimension) first and then expands, preferably self expands, to a second larger diameter (or transverse dimension) by about 0.1mm or more, or about 0.2mm or more, or about 0.3mm or more, or about 0.4 mm or more, or about 0.5 mm or more, without fracture.
  • the balloon expandable stent or tubular body or polymeric material expands to 1.0 times or more, or 1.1 times or more, or 1.2 times or more, or 1.3 times or more, or 1.4 times or more, or 1.5 times or more the deployed diameter or nominal diameter (or transverse dimension) at body temperature, without fracturing.
  • the stent or tubular body is crimped from an expanded diameter to a crimped configuration, and at body temperature is balloon
  • the stent or tubular body is crimped from an expanded diameter to a crimped configuration wherein the ratio of expanded diameter to crimped configuration is at least 1.5, and at body temperature the balloon expandable stent expands to 1.0 times or more, or 1.1 times or more, or 1.2 times or more, or 1.3 times or more, or 1.4 times or more, or 1.5 times or more the deployed diameter or nominal diameter (or transverse dimension), without fracturing.
  • An endoprosthesis e.g., a stent or a stent delivery system
  • the polymeric article/material e.g., a polymeric tube
  • ionizing radiation such as electron beam or gamma radiation
  • ethylene oxide gas e.g., for purposes of sterilization and/or treatment
  • Such modification or treatment in that it can, e.g., control crystallinity (e.g., degree of crystallinity), control Tg, control molecular weight, control monomer content, and/or enhance the strength of the material (e.g., polymeric material) comprising the polymeric article or the endoprosthesis.
  • the polymeric article and/or the endoprosthesis are exposed to a single dose or multiple doses of e-beam or gamma radiation totaling about 5 or 10 kGy to about 50 kGy, or about 20 kGy to about 40 kGy of radiation, e.g., a single dose of 30 kGy or multiple smaller doses (e.g., 3 x 10 kGy doses)], where the polymeric article and/or the endoprosthesis are optionally (cooled to low temperature (e.g., about -10 °C to about -30 °C, or about -20 °C to less than ambient temperature) for a period of time (e.g., at least about 1 minute, 20, 30 or 40 minutes) or optionally treated at about ambient temperature) prior to exposure to the single dose or to each of the multiple doses of radiation.
  • a single dose or multiple doses of e-beam or gamma radiation totaling about 5 or 10 kGy to about 50 kG
  • the polymeric article and/or the endoprosthesis are exposed to a single dose or multiple doses of e-beam or gamma radiation totaling about 10 kGy to about 50 kGy, or about 30 kGy.
  • a polymeric article and/or an endoprosthesis that have been exposed to ionizing radiation or ethylene oxide gas can also undergo one or more other modification treatments (e.g., heating or annealing and/or cooling) described herein.
  • the tubular body or polymeric material or stent may be formed from at least one polymer having desired degradation characteristics where the polymer may be modified to have the desired crystallinity, Tg, recoil, strength, shortening, expansion characteristics, crimping characteristics, crystallinity, Tg, molecular weight, and/or other characteristics in accordance with the methods of the present invention.
  • Polymers include one or more polymers, copolymers, blends, and combination thereof of: Lactides, Glycolides, Caprolactone, Lactides and Glycolides, Lactides and Caprolactones: examples poly-DL- Lactide, polylactide-co-glycolactide; polylactide-co-polycaprolactone, poly (L-lactide-co- trimethylene carbonate), polylactide-co-caprolactone, polytrimethylene carbonate and copolymers; polyhydroxybutyrate and copolymers; polyhydroxy valerate and copolymers, poly orthoesters and copolymers, poly anhydrides and copolymers, polyiminocarbonates and copolymers and the like.
  • a particularly preferred polymer comprises a copolymer of L- lactide and glycolide, preferably with a weight ratio of 85% L-lactide to 15% glycolide.
  • the tubular body or polymeric material or stent material comprises a degradable polymeric material wherein the polymeric material comprises one or more polymers; or one or more co-polymers; or one or more blends of monomers, polymers or copolymers; and combination thereof.
  • the polymeric material comprises one or more polymer or one or more co-polymer.
  • at least one monomer, polymer, or co-polymer of similar material is blended with the polymeric material.
  • a different monomer, co-polymer, or polymer is blended with (the one or more polymer or the one or more co-polymer) the polymeric material.
  • a biodegradable stent comprising a polymeric material comprising a copolymer of lactide and caprolactone in the ratio by weight ranging from 80-99% lactide to 1-20% caprolactone; wherein the polymeric material further comprises a monomer or polymer including copolymer of one or more of the following: lactide, glycolide, lactide glycolide, caprolactone, and lactide caprolactone; wherein the one or more monomer or polymer total amount is lto 100 micrograms per milligram of polymeric material, preferably 5 to 75 micrograms per milligram of polymeric material , more preferably 10 to 50 micrograms per milligrams of polymeric material; wherein the stent is capable to be crimped from an expanded configuration to a smaller crimped configuration, and at body temperature expanded to a deployed configuration, and having sufficient strength to support a body lumen, and without fracture of the stent.
  • a biodegradable stent comprising a polymeric material comprising a copolymer of lactide and caprolactone in the ratio by weight ranging from 80-99% lactide to 1-20% glycolide; wherein the polymeric material further comprises a monomer or polymer including copolymer of one or more of the following: lactide, glycolide, lactide glycolide, caprolactone, and lactide caprolactone;
  • the one or more monomer or polymer total amount is lto 100 micrograms per milligram of polymeric material, preferably 5 to 75 micrograms per milligram of polymeric material , more preferably 10 to 50 micrograms per milligrams of polymeric material;
  • the stent is capable to be crimped from an expanded configuration to a smaller crimped configuration, and at body temperature expanded to a deployed configuration, and having sufficient strength to support a body lumen, and without fracture.
  • the one or more monomer and/or polymer does not substantially change the crystallinity of the polymeric material.
  • the one or more monomer and/or polymer changes (increases or decreases) the crystallinity of the polymeric material by 5% to 150%, preferably by 10% to 75%, more preferably by 10% to 50%.
  • the one or more monomer and/or polymer controls the crystallinity of the polymeric material to between 1% and 55%, preferably between 1% and 35%.
  • the one or more monomer and/or polymer does not change the crystallinity of the polymeric material from being between 1% and 55%. In a further embodiment, the one or more monomer and/or polymer does not substantially change the Tg of the polymeric material. In a further embodiment, the one or more monomer and/or polymer changes (increases or decreases) the Tg temperature of the polymeric material by 1C to 15C, preferably 1°C to 10°C, more preferably by 1°C to 5°C.
  • the one or more monomer and/or polymer controls the Tg temperature of the polymeric material to between 20°C and 55°C, preferably to between 35°C and 50°C, more preferably to between 37°C and 50°C, most preferably between 37°C and 45°C.
  • the polymeric material/article and/or the tubular body and/or the prosthesis or device can undergo any of a variety of modification or treatments (e.g., longitudinal extension, longitudinal shrinkage, radial expansion, heating, cooling, quenching, pressurizing, exposure to or humidity, vacuuming, exposure or incorporation or removal of solvents, incorporation of additive, removal of additives, incorporation of or removal of impurities, exposure to radiation, incorporation or exposure or pressurization by gases such as carbon dioxide, or a combination thereof) designed to control or enhance characteristics (e.g., crystallinity, Tg, molecular weight, strength, toughness and degradation, recoil, shortening, expansion) of the article, the tubular body, the polymeric material, and/or the prosthesis or device.
  • the biodegradable implantable device formed from a polymeric article made by spraying, extrusion, dipping, molding, 3D printing, and the like, can have any features of a
  • biodegradable implantable device comprising a body comprising a biodegradable polymer (including homopolymer or copolymer) described herein.
  • a biodegradable polymer including homopolymer or copolymer
  • modification or treatment may include heating, and/or pressurizing.
  • the polymeric material is treated wherein the treatment comprises incorporation of solvents wherein the one or more solvent amounts in the polymeric material or the stent after treatment ranges from 0.001% to 10% by weight, preferably ranges from 0.1% to 5% by weight, more preferably ranges from 0.1% to 3% by weight.
  • the polymeric material is treated wherein the treatment comprises incorporation of solvents wherein the one or more solvent amounts in the polymeric material or the stent after treatment ranges from 0.001% to 10% by weight, preferably ranges from 0.1% to 3% by weight, more preferably ranges from 0.1% to 2% by weight and wherein the stent at body temperature is capable to expand from a crimped configuration to a deployed diameter without fracture and have sufficient strength to support a body lumen.
  • the polymeric material is treated wherein the treatment comprises incorporation of solvents wherein the one or more solvent amounts in the polymeric material or the stent after treatment ranges from 0.001% to 10% by weight, preferably ranges from 0.1% to 3% by weight, more preferably ranges from 0.1% to 2% by weight and wherein the one or more solvent substantially does not dissolve the stent (preferably does not dissolve the stent) and wherein the stent at body temperature is capable to expand from a crimped configuration to a deployed diameter without fracture and have sufficient strength to support a body lumen.
  • the polymeric material is treated wherein the treatment comprises incorporation of solvents wherein the one or more solvent amounts in the polymeric material or the stent after treatment ranges from 0.001% to 10% by weight, preferably ranges from 0.1% to 3% by weight, more preferably ranges from 0.1% to 2% by weight and wherein the one or more solvent preferably substantially does not dissolve the stent (preferably does not dissolve the stent) and wherein the one or more solvent substantially remains in the stent in the ranges described above before deployment of the stent )wherein the stent at body temperature is capable to expand from a crimped configuration to a deployed diameter without fracture and have sufficient strength to support a body lumen.
  • solvents include DCM, Chloroform to name some.
  • solvents that can be used for example are ones that dissolves the polymeric material when used in sufficient quantities or solvents that does not dissolve the polymeric material.
  • Preferred solvents are solvents that are retained in the polymeric material or stent after incorporation, or after treatment, or before deployment in the ranges described above.
  • Preferred Tg ranges from 20°C to 50°C, more preferred from greater than 37°C to less than 50°C.
  • Preferred crystallinity ranges from 1% to 60%, preferably from 1% to 55%, more preferably from 1% to 45%, most preferably from 1% to 35%.
  • the polymeric material preferably has an initial diameter, preferably 1-1.5 times the deployment diameter of the stent.
  • the stent is capable of being crimped from an expanded diameter to a crimped diameter, and at body temperature is capable to expand from a crimped configuration to a deployed diameter without fracture and have sufficient strength to support a body lumen.
  • polymeric material are materials comprising lactide, lactide and glycolide, or lactides and caprolactones, or a combination thereof.
  • the polymeric material is treated wherein the treatment comprises inducing or incorporation of monomers or polymers including co-polymers wherein the one or more monomers or polymers amounts in the polymeric material or the stent after treatment ranges from 0.001% to 10% by weight, preferably ranges from 0.1% to 5% by weight, more preferably ranges from 0.1% to 3% by weight.
  • the polymeric material is treated wherein the treatment comprises inducing or incorporation of monomers or polymers wherein the one or more monomers or polymers amounts in the polymeric material or the stent after treatment ranges from 0.001% to 10% by weight, preferably ranges from 0.1% to 5% by weight, more preferably ranges from 0.1% to 3% by weight and wherein the stent at body temperature is capable to expand from a crimped configuration to a deployed diameter without fracture and have sufficient strength to support a body lumen.
  • the polymeric material is treated wherein the treatment comprises inducing or incorporation of monomers or polymers wherein the one or more monomers or polymers amounts in the polymeric material or the stent after treatment ranges from 0.001% to 10% by weight, preferably ranges from 0.1% to 5% by weight, more preferably ranges from 0.1% to 3% by weight and wherein the one or more monomers or polymers substantially does not affect degradation of the stent (preferably does not affect degradation the stent.
  • the monomer or polymer accelerates degradation of the stent) and wherein the stent at body temperature is capable to expand from a crimped configuration to a deployed diameter without fracture and have sufficient strength to support a body lumen.
  • the polymeric material is treated wherein the treatment comprises inducing or incorporation of monomer or polymer wherein the one or more monomer or polymer amounts in the polymeric material or the stent after treatment ranges from 0.001% to 10% by weight, preferably ranges from 0.1% to 5% by weight, more preferably ranges from 0.1% to 3% by weight and wherein the one or more monomer or polymer preferably substantially does not affect the stent degradation (preferably accelerates the stent degradation) and wherein the one or more monomer or polymer substantially remains in the stent in the ranges described above before deployment of the stent )wherein the stent at body temperature is capable to expand from a crimped
  • the one or more monomer or polymer amounts in the polymeric material or the stent after treatment ranges from 0.1% to 10% by weight, preferably ranges from 1% to 5% by weight, more preferably ranges from 2% to 5%.
  • monomers or polymers examples include lactides, glycolides, caprolactones, lactides and glycolides, lactides and caprolactones to name a few. Incorporation of monomers can take place, for example by spraying as described herein, or inducing by radiation.
  • Preferred Tg ranges from 20°C to 50°C, more preferred from greater than 37°C to less than 50°C.
  • Preferred crystallinity ranges from 1% to 60%, preferably from 1% to 55%, more preferably from 1% to 45%, most preferably from 1% to 35%.
  • the polymeric material preferably has an initial diameter, preferably 1-1.5 times the deployment diameter of the stent.
  • the stent is capable of being crimped from an expanded diameter to a crimped diameter, and at body temperature is capable to expand from a crimped configuration to a deployed diameter without fracture and have sufficient strength to support a body lumen.
  • polymeric material are materials comprising lactide, lactide and glycolide, or lactides and caprolactones, or a combination thereof.
  • a method of making a biodegradable endoprosthesis comprising providing a polymeric article (e.g., a tubular body, such as a polymeric tube) comprising at least partially a substantially amorphous or semi-crystalline, biodegradable polymeric material, wherein crystallinity (e.g., degree of crystallinity) of the polymeric material increases after the polymeric article undergoes a modification (or treatment), and wherein the endoprosthesis is formed from the polymeric article.
  • the polymeric material is substantially amorphous or semi crystalline prior to the modification, and may or may not be substantially amorphous after the modification.
  • a method of making a biodegradable endoprosthesis comprising providing a polymeric article (e.g., a tubular body, such as a polymeric tube) comprising at least partially of a substantially amorphous or semi-crystalline biodegradable polymeric material, wherein crystallinity (e.g., degree of crystallinity) of the polymeric material decreases after the polymeric material undergoes a treatment, and wherein the endoprosthesis is formed substantially from the polymeric material.
  • the polymeric material is substantially amorphous or semi crystalline prior to the modification, and substantially amorphous after the modification.
  • the modification comprises heating, cooling, quenching, pressurizing, vacuuming, crosslinking, addition of an additive, or exposure to radiation or carbon dioxide, or a combination thereof.
  • the polymeric article can have any shape, form and dimensions suitable for making the endoprosthesis (e.g., a patterned polymeric tube stent).
  • treatment comprises a heat treatment preferably at about initial diameter to a temperature above its glass transition temperature of the polymeric material and below its melting point for a period ranging from a fraction of a second to 7 days.
  • the polymeric material or the tubular body in one embodiment may be cooled after heating to a temperature ranging from below ambient temperature to ambient temperature over a period ranging from a fraction of a second to 7 days.
  • the polymeric material or the tubular body initial diameter is approximately 1-1.5 times the stent
  • the polymeric material or the tubular body is treated at diameter between initial diameter and crimped diameter.
  • the treatment comprises heating the tubular body to a temperature about or below Tg for a period ranging from a fraction of a second to 7 days.
  • the heat treatment at the below initial diameter comprises heat treatment about or above Tg and below Tm for a period ranging from a fraction of a second to 5 hours, or preferably less than 2 hour, or most preferably less than 60 minutes.
  • the polymeric material or the tubular body after forming is treated comprising heat at temperature about or less than Tg.
  • the tubular body after forming and excluding patterning is treated comprising heat at temperature about or less than Tg. In some cases, the treatment is about Tm or higher. Examples of methods of forming the stent polymeric material are by injection molding or 3D printing. Durations are similar to above ranges. Other suitable temperatures and times are described herein.
  • the diameter of the tubular body or the polymeric material or the stent may, at the time of treatment (e.g., treatment diameter), be optionally smaller or optionally greater than the deployment diameter, where the deployment diameter may include, for example, the diameter of the tubular body or the stent within a lumen.
  • the treatment diameter may be 1-2 times the deployment diameter, or 1-1.9 times the deployment diameter, or 1-1.8 times the deployment diameter, or 1-1.7 times the deployment diameter, or 1-1.6 times the deployment diameter, or 1-1.5 times the deployment diameter, or 1-1.4 times the deployment diameter, or 1-1.3 times the deployment diameter, or 1-1.2 times the deployment diameter, or 1-1.05 times the deployment diameter.
  • the treatment diameter may be 0.95-1 times the deployment diameter.
  • the treatment diameter may be 0.9-1 times the deployment diameter, or 0.8-1 times the deployment diameter, or 0.7-1 times the deployment diameter, or 0.6-1 times the deployment diameter, or 0.5-1 times the deployment diameter, or 0.4-1 times the deployment diameter, or 0.3-1 times the deployment diameter, or 0.2-1 times the deployment diameter.
  • the stent expanded/deployed diameter typically is 2mm and higher, 2.5mm and higher, 3mm and higher, 3.5mm and higher, 4mm and higher, 4.5mm and higher, 5mm and higher, 5.5mm and higher.
  • the stent deployed diameter ranges from 2mm-25mm, preferably ranges from 2.5mm to 15mm, more preferably from 3mm to 10mm.
  • the stent length ranges from 1mm to 200cm, preferably from 5mm to 60cm, more preferably from 5mm to 6cm.
  • biodegradable implantable devices comprising a polymeric material, or a body (e.g., a tubular body) that comprises one or more biodegradable polymeric materials to achieve a desired Tg.
  • the treated polymeric material or the tubular body has a desired Tg.
  • the tubular body or polymeric material is treated to control Tg.
  • the tubular body is treated to control Tg and crystallinity.
  • the tubular body is treated to control Tg, crystallinity, and molecular weight.
  • the one or more materials comprising the body, or the stent, or the stent material, or the tubular body or the polymeric material may have a wet or dry glass transition temperature (T g ) greater than 20°C, or greater than 30°C, or greater than 31°C, or greater than 32°C, or greater than 33°C, or greater than about 34°C, or greater than 35°C, or greater than 36°C, or greater than 37°C.
  • T g wet or dry glass transition temperature
  • the one or more materials comprising the body, or the stent, or the tubular body have a T g less than 45°C, or less than 44°C, or less than 43°C, or less than 42°C, or less than 41°C, or less than 40°C, or less than 39°C, or less than 38°C, or less than 37°C, or less than 36°C.
  • the one or more materials comprising the body, or the stent, or the tubular body have a T g of about 20°C to about 55°C, or about 20°C to about 50°C, or about 31°C to about 45°C, or about 32°C to about 45°C, or about 33°C to about 45°C, or about 34°C to about 45°C, or about 35°C to about 45°C, or about 36°C to about 45°C, or about 37°C to about 45°C, or about 38°C to about 45°C, or about 39°C to about 45°C, or about 40°C to about 45°C.
  • the one or more materials comprising the body, or the stent, or the tubular body have a T g of about 20°C to about 45°C, or about 30°C to about 44°C, or about 30°C to about 43°C, or about 30°C to about 42°C, or about 30°C to about 41°C, or about 30°C to about 40°C, or about 30°C to about 39°C, or about 30°C to about 38°C, or about 30°C to about 37°C.
  • the one or more materials comprising the body, or the stent, or the tubular body has a T g greater than 37°C and less than 45°C, or greater than37°C and less than 40°C, or greater than 37°C to less than 50°C, or greater than 37°C to less than 55°C, or greater than 38 °C to less than 50 °C, or greater than 40 °C and less than 50 °C, or greater than 45 °C and less than 50 °C.
  • the one or more materials comprising the body, or the polymeric material, or the stent, or the stent material, or the tubular body has a T g greater than 35°C and less than 45°C, or greater than 36°C and less than 45°C, or greater than 37°C and less than 45°C, or greater than 37°C and less than 40°C or greater than 20°C and less than 45°C, or greater than 35°C and less than or equal to 45°C.
  • the one or more biodegradable polymeric materials or the tubular body or the stent material has elastic modulus at body temperature (in aqueous or water or dry) of 0.2GPa to 20GPa, or of 0.3GPa to 5Pa, or greater than 0.35GPa and less than 3GPa, or of 0.4 GPa to 2.5GPa, or of about 0.5Pa to about IGPa, or of about 0.35GPa to about 0.85GPa, or of about 0.40GPa to about 0.75GPa, or of about 0.45Pa to about 0.70Pa, or of about 0.50GPa to about 0.65GPa, or at least 0.2GPa, or at least 0.3GPa, or at least 0.4GPa, or at least 0.5GPa.
  • the one or more biodegradable polymeric materials, or the tubular body or the stent may have a percent elongation at break at body temperature (in aqueous or water or dry)of 20% to 800%, or of about 20% to about 300%, or of about 20% to about 200%, or of about 20% to about 100%, or of about 20% to about 50%, or of about 10% to about 600%, or of about 10% to about 300%, or of about 5% to about 600%, or of about 5% to about 300%, or of about 1% to about 600%, or of about 1% to about 300%, or of about 1% to about 200%, or of about 1% to about 150%;
  • the polymeric material comprising the body of the device or the biodegradable polymer, or copolymer or polymer blend, or the tubular body
  • the biodegradable polymeric material or the stent material comprising the biodegradable polymeric material or the stent material; has a tensile yield strength of at least 1500 psi, or at least 2000 psi, or at least 2500 psi, or at least 3000 psi, or at least 4000psi, or at least 5000 psi.
  • the polymeric stent material has a tensile yield strength ranging from 1500 psi to 6000psi, or between 200psi and 5000psi.
  • the biodegradable polymeric material or the tubular body or the stent material has stiffness of at least lOOOMPa, or at least 1500MPa, or at least 2000MPa, or at least 2500MPa, or at least 3000MPa, or at most 5000MPa, or at most 4000MPa; when measured at body temperature (in aqueous or water or dry).
  • the biodegradable polymeric material or the tubular body or the stent material has elastic modulus of at least 250MPa, or at least 350MPa, or at least 400MPa, or at least 450MPa, or at least 500MPa; when measured at body temperature (in aqueous or water or dry).
  • the material comprising the body or the biodegradable polymer or copolymer or polymer blend, or the tubular body comprising the biodegradable polymer, or the stent has a percent elongation at break when measure at body temperature (wet or dry) of about 20% to about 800%, or of about 20% to about 300%, or of about 20% to about 200%, or of about 20% to about 100%, or of about 20% to about 50%, or of about 10% to about 600%, or of about 10% to about 300%, or of about 5% to about 600%, or of about 5% to about 300%, or of about 1% to about 600%, or of about 1% to about 300%, or of about 1% to about 200%, or of about 1% to about 150%;.
  • the biodegradable polymer, copolymer or polymer blend or tubular body comprising the biodegradable polymer material or stent prosthesis material has stiffness at body temperature (in aqueous or water or dry) of about 0.4N/mm2 to about 2N/mm2, or of about 0.5N/mm2 to about 1.5N/mm2, or of about 0.7N/mm2 to about 1.4N/mm2, or of about 0.8N/mm2 to about 1.3N/mm2.
  • the biodegradable polymer or copolymer or polymer blend or tubular body comprising the biodegradable polymer material or prosthesis has elastic modulus at body temperature, of about 0.2GPa to about 20GPa, or of about 0.3GPa to about 5PGa, or of about 0.4 GPa to about 2.5GPa, or of about 0.5GPa to about lGPa, or at least 0.2GPa, or at least 0.3GPa, or at least 0.4GPa, or at least 0.5GPa.
  • the biodegradable polymer or copolymer or polymer blend or tubular body comprising the biodegradable polymer material or prosthesis material; has yield strain at body temperature of at most 20%, or at most 15%, preferably at most 10%, more preferably at most 5%, at body temperature (in aqueous or water or dry).
  • the prosthesis has radial strength sufficient to support a body lumen.
  • the biodegradable polymer or copolymer or tubular body or stent prosthesis has a radial strength in an aqueous
  • the biodegradable polymer or copolymer or tubular body or stent prosthesis has a radial strength at body temperature (in aqueous or water or dry) of greater than 2psi, or greater than 8psi, or greater than lOpsi, or greater than 15psi.
  • Radial strength can be measured in a variety of methods known in the art. For example the flat plate method or iris method or other known methods.
  • Radial force can be measured with several methods known in the art. For example when the stent radial strength is not sufficient to support a body lumen, or the expanded diameter is reduced by a substantial amount, or reduced by at least 15%, or reduced by at least 20%, or reduced by at least 25%, or reduced by at least 50%.
  • the biodegradable copolymer, or polymer blend, or polymer, or tubular body comprising the biodegradable polymer, or prosthesis has a % recoil in an aqueous environment at 37°C of about -20% to about 20%, or of about- 15% to about 15%, or of about -10% to about 10%, or of about -10% to about 0%, or of about 3% to about 10%, or of about 4% to about 9%, or less than 25%, or less than 20%, or less than 15%, or less than 10%, or less than 5%; after expansion from a crimped state.
  • % recoil is measured in a variety of ways in-vitro or in- vivo with methods known in the art.
  • in-vitro % recoil can be measured by expanding the stent in an aqueous environment at about 37 °C inside a tube or unconstrained and measuring % recoil after expansion using laser micrometer.
  • in-vivo % recoil measurement using QCA see, e.g., Catheterization and Cardiovascular Interventions, 70:515-523 (2007).
  • the biodegradable polymer or copolymer or tubular body or prosthesis has a radial strength (in an aqueous environment or dry at 37°C from about 1 minute to about lday after expansion) of about 2psi to about 25psi; wherein the radial strength increases by about lpsi to about 20 psi, or by about 2 psi to about 15psi, or by about 3 psi to about lOpsi, or by about 4 psi to about 8 psi, after being in such an aqueous or dry environment for about 1 day to about 60 days.
  • the biodegradable, polymer, or copolymer, or polymer blend, or tubular body, or stent material is substantially amorphous, or substantially semi crystalline, or substantially crystalline; after modification, or before modification, or after radiation, or before implantation into a mammalian body lumen.
  • the biodegradable polymer, or copolymer or polymer blend, or tubular body, or stent is substantially amorphous before and after modification, or substantially amorphous before a modification and substantially semi crystalline after modification, or substantially amorphous before a modification and substantially crystalline after modification, or substantially semi crystalline before a modification and substantially amorphous after modification, or substantially semi crystalline before a modification and substantially semi crystalline after modification, or substantially semi crystalline before a modification and crystalline after modification, or substantially crystalline before modification and substantially semi crystalline after a modification, or substantially crystalline before modification and substantially semi crystalline after a modification, or substantially crystalline before a modification and substantially amorphous after a modification, or substantially crystalline before a modification, or substantially crystalline before a modification and substantially amorphous after a modification, or substantially crystalline before a
  • the biodegradable polymer or copolymer or polymer blend or tubular body or stent has longitudinal shrinkage of about 0% to about 30%, or of about 5% to about 25%, or of about 7% to about 20%, or of about 10% to about 15%; when heated (e.g. in an oven) at temperatures ranging from about 30°C to about 150°C (with or without a mandrel inserted into the copolymer or tubular body or prosthesis for a time ranging from about 30 minutes to about 24 hours); or upon or after expansion of the stent from a crimped state to an expanded state at body temperature.
  • the longitudinal shrinkage is less than 30%, or less than 25%, or less than 20%, or less than 15%, or less than 10%, of the original length upon or after expansion of the stent from a crimped state to an expanded state at body temperature.
  • the stent or polymer material or polymer tube has longitudinal shrinkage of less than about 25% or less, or about 15% or less, or about 10% or less, or about 5% or less, or about 1-25%, or about 5-15%, after being in aqueous condition at about 37 °C in vitro or in vivo for about 1 minute or less, or about 5 minutes or less, or about 15 minutes or less, or after expansion from the crimped state at body temperature.
  • the stent or polymer material or polymer tube has longitudinal shrinkage of less than about 25% or less, or about 15% or less, or about 10% or less, or about 5% or less, or about 1-25%, or about 5-15%, after being in aqueous condition at about 37°C in vitro or in vivo for about 1 minute or less, or about 5 minutes or less, or about 15 minutes or less, or after expansion from the crimped state.
  • the stent or polymeric material or tubular body has longitudinal lengthening of less than 25%, or 15% or less, or 10% or less, or 5% or less, or 1-25%, or 5-15%, after being in aqueous condition at about 37 °C in vitro or in vivo for about 1 minute or less, or about 5 minutes or less, or about 15 minutes or less, or after expansion from the crimped state at body temperature.
  • the amorphous, or semicrystalline, or crystalline polymeric material has internal stresses, or longitudinal shrinkage of no more than 15% from before a modification to after modification.
  • the polymer comprises a polymer, or a co-polymer, or a blend of polymers, or a mixture of polymers, or a blend of polymer and at least one monomer, or a blend of co-polymer and at least one monomer, or a combination thereof.
  • the polymer blend, copolymer, or mixture of polymers substantially does not exhibit phase separation.
  • the polymer or tubular body or prosthesis is porous; such that it will grow in the radial direction by about 0.025mm to about 1mm when soaked in an aqueous or dry environment at about 37°C from about 1 minute to about 15 minutes.
  • the copolymer material, or tubular body, or prosthesis has a textured surface, or non uniform surface, or surface with ridges, or bumpy surface, or surface with grooves, or wavy surface.
  • the distance between the peak and trough of the surface texture range from about 0.01 micron to about 30 micron, or from about 0.1 micron to about 20 micron, or from about 1 micron to about 15 micron.
  • the one or more biodegradable polymeric materials, or the tubular body or the stent may have a radial strength in an aqueous environment at about 37°C of about 2 psi to about 25 psi, or of about 5 psi to about 22 psi, or of about 7 psi to about 20 psi, or of about 9 psi to about 18 psi.
  • the biodegradable polymer or copolymer or tubular body or prosthesis has a radial strength in an aqueous or dry environment at body temperature of, greater than 3 psi, or greater than 5 psi, or greater than 8psi, or greater than lOpsi, or greater than 15psi.
  • the biodegradable copolymer, or polymer blend, or polymer, or tubular body comprising the biodegradable polymer, or prosthesis has a % recoil in an aqueous or dry environment at 37°C of about -20% to about 20%, or of about -15% to about 15%, or of about -10% to about 10%, or of about -10% to about 0%, or of about 3% to about 10%, or of about 4% to about 9%, or about 10% to about 20%, or about 15% to about 20%, or about 10% to about 15% or less than 25%, or less than 20%, or less than 15%, or less than 10%, or less than 5% after expansion to a deployed
  • the one or more biodegradable polymeric materials, or the tubular body, or the stent may optionally undergo treatment such as heating.
  • the one or more biodegradable polymeric materials, or the tubular body, or the stent may undergo longitudinal shrinkage of about 0% to about 30%, or of about 5% to about 25%, or of about 7% to about 20%, or of about 10% to about 15%.
  • the longitudinal (e.g., scaffold) shrinkage is less than 30%, or less than 25%, or less than 20%, or less than 15%, or less than 10%, of the original length.
  • the stent or polymer material or polymer tube has longitudinal shrinkage of about 25% or less, or about 15% or less, or about 10% or less, or about 5% or less, or about 0-30%, or about 1-25%, or about 5-15%.
  • treatment may include heating (e.g.
  • the material comprising the body of the device or the biodegradable polymer, copolymer or polymer blend, or the tubular body comprising the biodegradable polymer, or the stent is, or has crystals, crystalline regions, or polymer chains that are: substantially not uniaxially oriented, or not circumferentially oriented, or not longitudinally oriented, or not biaxially oriented.
  • the biodegradable copolymer has crystals, crystalline regions, molecular architecture, structural order, orientation, or polymer chains that are: substantially not uniform, or has low degree of order, or has varying degree of order, or is not substantially oriented as a result of not performing at least one of pressurizing and stretching of the tubular body, or is at least partially oriented as a result of spraying or dipping or crystallization or recrystallization, or radiation, or is at least partially oriented as a result of solvent evaporation or annealing or radiation, or is
  • the biodegradable copolymer has crystals, crystalline regions, molecular architecture, structural order, orientation, or polymer chains that are: substantially oriented, or oriented, or biaxially oriented, or uniaxially oriented, or oriented in a direction that is longitudinal, or oriented in a direction that is circumferential, or oriented in a direction that is not longitudinal or circumferential, or oriented as a result of at least one of pressurizing the tube or stretching or drawing the tube, or oriented as a result of modification or treatment.
  • the material comprising the body of the device or the biodegradable polymer, copolymer or polymer blend, or the tubular body comprising the biodegradable polymer, or the stent is, or has crystals, crystalline regions, or polymer chains that are: substantially not uniaxially oriented, or circumferentially oriented, or longitudinally oriented, or biaxially oriented.
  • the biodegradable copolymer has crystals, crystalline regions, molecular architecture, structural order, orientation, or polymer chains that are: substantially not uniform, or has low degree of order, or has varying degree of order, or is not substantially oriented as a result of not performing at least one of pressurizing and stretching of the tubular body, or is at least partially oriented as a result of spraying or dipping or crystallization or recrystallization, or radiation, or is at least partially oriented as a result of solvent evaporation or annealing or radiation, or is substantially not oriented, or not uniformly oriented, or low order oriented, or varying degree oriented, or randomly oriented, as a result of spraying or dipping, or solvent evaporation, or annealing, or radiation, or crystallization or recrystallization.
  • the biodegradable copolymer has crystals, crystalline regions, molecular architecture, structural order, orientation, or polymer chains that are: substantially oriented, or oriented, or biaxially oriented, or uniaxially oriented, or oriented in a direction that is longitudinal, or oriented in a direction that is circumferential, or oriented in a direction that is not longitudinal or circumferential, or oriented as a result of at least one of pressurizing the copolymer tube or stretching or drawing the tube, or oriented as a result of modification or treatment.
  • controlling the orientation of the polymeric material achieves the desired crystallinity, or Tg.
  • the polymeric material orientation is controlled such that the stent is capable to be crimped from an expanded condition to a crimped condition.
  • the polymeric material orientation is controlled such that the stent is capable to be expanded to a deployed diameter from a crimped configuration.
  • the polymeric material orientation is controlled such that the stent is capable to be expanded from a crimped configuration to a deployed configuration without fracture.
  • the polymeric material orientation is controlled such that the material has sufficient strength to support a body lumen.
  • the polymeric material orientation is controlled by pressurizing the polymeric material with a medium such as gas such as C0 2 wherein the orientation control affects crystallinity to a range from 1% to 35%, or 1% to 45%, or 1% to 55%.
  • the material comprising the body of the device or the biodegradable copolymer or polymer has a weight-average molecular weight (Mw) of at least about 30,000 daltons (30 kDa), 60,000 daltons, 90 kDa, 120 kDa, 150 kDa, 180 kDa, 210 kDa, or 240 kDa, or 500kDa, or 750 kDa, or lOOOkDa.
  • Mw weight-average molecular weight
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer or polymer has an M w of at least about 120 kDa.
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer or polymer has an M w of about 30 kDa to about 800 kDa, or about 30 kDa to about 700 kDa, or about 30 kDa to about 600 kDa, or about 30 kDa to about 500 kDa, or about 30 kDa to about 400 kDa, or about 30 kDa to about 300 kDa, or about 60 kDa to about 900 kDa, or about 90 kDa to about 600 kDa, or about 120 kDa to about 400 kDa, or about 150 kDa to about 250 kDa, or about 80 kDa to about 250 kD
  • the material e.g., polymeric material
  • the material comprising the body of the device or the biodegradable copolymer or polymer has a M w of about 120 kDa to about 250 kDa; before treatment, or after treatment, of the stent prosthesis.
  • biodegradable polymeric materials may be copolymers, such as block copolymers or random copolymers. In some embodiments, two or more
  • biodegradable polymeric materials may be used as part of a tubular body or prosthesis or stent (e.g., as a polymer blend). In some cases, co-polymeric and homopolymeric materials may be blended. Biodegradable polymeric materials may include poly-DL-lactide, polylactide-co-glycolactide, or other polymers as described herein. In some embodiments, the tubular body or prosthesis or stent may also include one or more monomers of the polymers that comprise the stent, or of other polymers. In some cases, the one or more monomers may be covalently bonded to the one or more polymers.
  • the two or more biodegradable polymeric materials may remain in substantially the same phase after about 1 second, or 10 seconds, or 1 minute, or 10 minutes, or 1 hour, or 10 hours, or 1 day, or 10 days, or 1 month, or 6 months, or 1 year, or 2 years, or 5 years of deployment and/or treatment.
  • the two or more biodegradable polymeric materials may have a T g within 2°C, or within 4°C, or within 6°C, or within 8°C, or within 10°C, or within 12°C, or within 14°C, or within 16°C, or within 18°C, or within 20°C of each other.
  • the polymeric material comprises monomer. In further embodiments, the polymeric material comprises less than 10% (by weight), or less than 5% (by weight), or less than 1% (by weight), or less than 0.5% (by weight), or less than 0.25% (by weight) monomer. In other embodiments, the polymeric material comprises 0-10% (by weight) of monomer.
  • the polymeric material comprises one or more copolymers, and to this polymeric material is added about 0.1% or less, or about 0.5% or less, or about 1% or less, or about 2% or less, or about 3% or less, or about 4% or less, or about 5% or less, or about 6% or less, or about 7% or less, or about 8% or less, or about 9% or less, or about 10% or less monomer.
  • the polymeric material further comprising one or more of the co-polymers, or another monomer, or another polymer, or another co-polymer.
  • the addition of monomer, polymer or copolymer does not change the Tg of the polymeric material substantially.
  • the addition of monomer, polymer, or copolymer does not change the Tg of the polymeric material by more than 10°C, or by more than 5°C, or by more than 3°C than the polymeric material without added monomer, polymer, or copolymer.
  • the addition of monomer, polymer, or copolymer does not exhibit phase separation from the polymeric material after treatment and/or before deployment.
  • the polymeric material comprises less than about 100 micrograms, or less than about 50 micrograms, or less than about 25 micrograms or monomer (such as unreacted monomer), polymer, or copolymer per milligram of stent.
  • the addition of monomer, polymer or copolymer does not interfere with the expansion of stent from crimped state to expanded state, and the expansion can occur without fracture.
  • the addition of monomer, polymer, or copolymer does not change crystallinity of the polymeric material, which may be more than about 1% and less than about 30%, or more than about 0% and less than about 35%, or less than 35%, or less than 30%, or less than 25%, or less than 20%, or less than 15%, or less than 10%, or less than 5%, or greater than 0%, or greater than 5%, or greater than 10%, or greater than about 15%, or greater than about 20%, or greater than about 25%, or greater than about 30%, or greater than about 35%.
  • combination of polymeric material and monomer, polymer, or copolymer comprising the body, or the stent, or the tubular body may have a crystallinity of about 0% to less than 35%, or about 0% to less than 30%, or about 0% to less than 25%, or about 0% to less than 20%, or about 0% to less than 15%, or about 0% to less than 10%, or about 0% to less than 5%.
  • addition of monomer, polymer or copolymer does not change the molecular weight of the polymeric material, which can be in the range from about 30 kDa to about 700 kDa.
  • the unreacted monomer, polymer or copolymer comprises glycolic acid, lactide, polyglycolic acid, lactide-co-glycolide, caprolactone, polycaprolactone, lactide-co-caprolactone, and combinations thereof.
  • the biodegradable stent or tube comprises a body which comprises a biodegradable polymer, or copolymer, polymer blends, copolymers, and/or polymer/monomer mixtures wherein the polymer material is configured to be capable of being balloon expandable and self-expanding at body temperature of about 37°C.
  • the stent prior to being balloon-expanded, may self-expand by about 0.001- 0.025 inches, or about 0.003-0.015 inches, or about 0.005-0.10 inches, or about 0.001 inches or more, or 0.003 inches or more, or 0.005 inches or more, or 0.010 inches or more, or 0.025 inch or more, or by about 0.05%, or about 0.1%, or about 0.25%, or about 0.5%, or about 1%, or more than an initial crimped diameter of the stent, after being in aqueous condition at about 37 °C in vitro or in vivo for about 1 minute or less, or about 5 minutes or less, or about 15 minutes or less, or about 30 minutes or less, or about 1 hour or less, or about 2 hours or less, or about 3 hours or less, or about 4 hours or less, or about 6 hours or less, or about 12 hours or less, or about one day or less.
  • the stent is constrained from self- expanding using a sheath or other means and then such constraining means is removed, disengaged, or withdrawn, or released after the stent is positioned for deployment, allowing the stent to self-deploy.
  • the stent in a preferred embodiment further self expands after balloon deployment by about 0.01 mm to about 0.5mm, or about 0.05 mm to about 0.3 mm, within about 30 seconds or more, or about 1 minute or more, or about 10 minutes or more, or about 1 hour or more, or about 12 hours or more, or about 24 hours or more.
  • the one or more biodegradable polymeric materials, or the tubular body, or the stent degrade over time. Degradation may occur in vitro or in vivo.
  • Degradation may occur after about 1 day, or about 5 days, or about 10 days, or about 1 month, or about 2 months, or about 6 months, or about 1 year in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37 °C in vitro or in vivo.
  • aqueous condition e.g., in aqueous solution, water, saline solution or physiological conditions
  • the one or more biodegradable polymeric materials or the tubular body may substantially degrade within 2 years, or 1.5 years, or 1 years, or 9 months, or 6 months.
  • the body of the device, or the stent, or the material comprising the body of the device, or the material comprising one or more layers of the body of the device comprises one or more biologically active agents.
  • the biologically active agent(s) are selected from the group consisting of anti-proliferative agents, anti-mitotic agents, cytostatic agents, anti-migratory agents, immunomodulators,
  • the body of the device comprises an anti-proliferative agent, antimitotic agent, cytostatic agent or anti-migratory agent.
  • the body of the device comprises an anticoagulant, anti-thrombotic agent, thrombolytic agent, anti- thrombin agent, anti-fibrin agent or anti-platelet agent in addition to an anti-proliferative agent, anti-mitotic agent, cytostatic agent or anti-migratory agent.
  • an anti-proliferative agent anti-mitotic agent
  • cytostatic agent anti-migratory agent
  • specific examples of biologically active agents disclosed herein may exert more than one biological effect.
  • anti-proliferative agents, anti-mitotic agents, cytostatic agents and anti-migratory agents include without limitation rapamycin and its derivatives and metabolites.
  • the stent or body of the device can comprise one or more biologically active agents, and/or one or more additives such as carbon nano fibers or tubes.
  • the additives can serve any of a variety of functions, including controlling degradation, increasing the strength, increasing elongation, controlling Tg, or/and increasing toughness of the material (e.g., polymeric material) comprising the body of the device (or the material comprising a coating on the body), and/or increasing crystallinity.
  • the stent or tubular body comprises radiopaque markers.
  • Radiopaque markers can be metallic such as gold, platinum, iridium, bismuth, or combination thereof, or alloys thereof. Radiopaque markers can also be polymeric material. Radiopaque markers can be incorporated in the stent or tubular body when it is being formed or incorporated into the stent or the tubular body after forming.
  • one or more coatings can be applied onto the body of the device.
  • Each of the coatings can contain one or more biodegradable polymers, one or more non-degradable polymers, one or more metals or metal alloys, one or more biologically active agents, or one or more additives, or a combination thereof.
  • the coating(s) can serve any of a variety of functions, including controlling degradation of the body of the device, improving or controlling physical characteristics (e.g., strength, recoil, toughness) of the device, and delivering one or more biologically active agents to a site of treatment.
  • the biodegradable implantable device described herein can be used to treat or prevent a wide variety of diseases, disorders and conditions, or promote a wide variety of therapeutic effects.
  • the biodegradable device is implanted in a subject for treatment or prevention of a disorder or condition, or delivery or a drug, or promotion of a therapeutic effect, selected from the group consisting of wound healing, hyper-proliferative disease, cancer, tumor, vascular disease, cardiovascular disease, coronary artery disease, peripheral arterial disease, ENT or nose disorder, atherosclerosis, thrombosis, vulnerable plaque, stenosis, restenosis, ischemia, myocardial ischemia, peripheral ischemia, limb ischemia, hyper-calcemia, vascular obstruction, vascular dissection, vascular perforation, aneurysm, vascular aneurysm, aortic aneurysm, abdominal aortic aneurysm, cerebral aneurysm, chronic
  • biodegradable device can also be used outside the body, e.g., in tissue engineering to generate tissue.
  • the stent can also be used to treat or prevent a wide variety of diseases, disorders and conditions.
  • the stent can also be used to treat or prevent a wide variety of diseases, disorders and conditions.
  • the stent can also be used to treat or prevent a wide variety of diseases, disorders and conditions.
  • biodegradable stent is implanted in a subject for treatment or prevention of obstruction, occlusion, constriction, stricture, narrowing, stenosis, restenosis, intimal hyperplasia, collapse, dissection, thinning, perforation, kinking, aneurysm, failed access graft, cancer or tumor of a vessel, passage, conduit, tubular tissue or tubular organ, such as an artery, vein, peripheral artery, peripheral vein, subclavian artery, superior caval vein, inferior caval vein, popliteal artery, popliteal vein, arterial duct, coronary artery, carotid artery, brain artery, aorta, ductus arteriosus, right ventricular outflow tract conduit, transitional atrioventricular canal, interatrial septum, iliac artery, common iliac artery, external iliac artery, internal iliac artery, iliac vein, internal pudendal artery, mammary artery, femoral
  • the biodegradable device is an endoprosthesis or stent.
  • stents include vascular stents, coronary stents, coronary heart disease (CHD) stents, carotid stents, brain aneurysm stents, peripheral stents, peripheral vascular stents, venous stents, femoral stents, superficial femoral artery (SFA) stents, pancreatic stents, renal stents, biliary stents, intestinal stents, duodenal stents, colonic stents, ureteral stents, urethral stents, prostatic stents, sphincter stents, airway stents, tracheobronchial stents, tracheal stents, laryngeal stents, esophageal stent
  • the endoprosthesis design and pattern can be any suitable pattern of the type employed in conventional endoprostheses to serve the intended purpose of the device.
  • a variety of exemplary patterns are set forth in (but not limited to) U.S. Pat. App. Ser. No. 12/016,077, which is incorporated herein by reference in its entirety.
  • the material comprising or comprising the body of the biodegradable implantable device or the biodegradable copolymer or polymer:
  • % crystallinity by XRD or DSC has a degree of crystallinity, or % crystallinity by XRD or DSC, of about 5% to about 30% by weight or volume;
  • T g has a T g of greater than 37 °C and less than 50 °C;
  • % elongation at break or failure or yield of about 15% to about 300%; and radially expandable from crimped configuration to expanded configuration without fracture at body temperature.
  • the material comprising the body of the biodegradable implantable device or the biodegradable copolymer or polymer:
  • % crystallinity by XRD or DSC has a degree of crystallinity, or % crystallinity by XRD or DSC, of about 30%;
  • T g has a T g of greater than 37 °C to less than 47 °C;
  • % elongation at break or failure or yield has a % elongation at break or failure or yield of about 15% to about 300%.
  • the biodegradable devices and the biodegradable polymers have a rough exterior, or texture as depicted in Figure 5A for example.
  • the preferred texture is such that the surface has several bumps, or/and such bumps are not oriented in an uniform manner.
  • This texture can be achieved in a variety of ways including spraying as an example.
  • Such texture is different from the texture show in Figure 5B, wherein the texturing has an orientation, in this case the orientation being in the horizontal direction.
  • Such horizontally oriented texturing is in some embodiments can be achieved by die extrusion.
  • the biodegradable devices and the biodegradable polymers have both types of texturing described herein. In a preferred embodiment, orientation of the device may be controlled.
  • the stent is deployed in a main vessel across a side branch, and the stent of the invention allows for insertion of a guidewire and/or balloon catheter through openings between stent struts, and enabling inflation through the openings of stent struts to increase or expand interstrut opening to the branch.
  • the stent allows for a guidewire and/or balloon catheter through the opening to expand at least one transverse dimension to access and treat the side branch with balloon inflation, or additional stent implantation or drug delivery treatments.
  • the stent expanded diameter/ transverse dimension in one embodiment is substantially maintained after balloon expansion and removal of the balloon. In another embodiment, the expanded diameter/ transverse dimension is decreased after balloon expansion and removal of the balloon. In a preferred embodiment, the decrease is at least 20% from the expanded transverse dimension. In a preferred embodiment, the decrease is at least 20% from the expanded transverse dimension and less than 75%.
  • a third is substantially maintained after balloon expansion and removal of the balloon. In another embodiment, the expanded diameter/ transverse dimension is decreased after balloon
  • the expanded transverse dimension becomes larger after balloon expansion and removal of the balloon, preferably larger by at least 1%, or by at least 5%, or by at least 10% from the balloon expanded transverse dimension.
  • changes in the transverse dimension occur within 24 hours or less, or 12 hours or less, or 9 hours or less, or 6 hours or less, or 3 hours or less, or 1 hour or less, or 30 minutes or less.
  • the stent struts are capable of expanding along one or more than one dimension or directional dimension upon balloon inflation through the stent strut openings along the longitudinal, radial, or circumferential dimensions.
  • the stent struts are capable to expand in one or more transverse dimensions without fracture.
  • the expanded transverse dimension of the stent struts remains substantially the same, and without fracture.
  • the expanded transverse dimension of the stent struts further expands or increase, and without fracture.
  • the expanded transverse dimension of the stent struts further contracts or decrease, and without fracture.
  • the balloon expands stent struts in at least the radial transverse dimension further self expands to align with vessel wall, or self expand to oppose the vessel wall, or self expands by at least 0.01mm.
  • the invention provides polymeric materials, including biodegradable stents, and methods of their fabrication.
  • Various aspects of the invention described herein may be applied to any of the particular applications set forth below or in any other type of setting.
  • the invention may be applied as a standalone system or method, or as part of an integrated system or method. It shall be understood that different aspects of the invention can be appreciated individually, collectively, or in combination with each other.
  • Figure 1 depicts an example of stent pattern having substantially W and/or V-shaped cells
  • Figure 2 illustrates an example of raised portions (poofs) formed on the balloon of a balloon-catheter which hold, cap and/or extend over the proximal and/or distal ends of a stent to retain the stent substantially in place on the balloon during delivery;
  • Figure 3 depicts an example of stent pattern having lockable elements that are designed to retain the stent on a balloon-catheter
  • Figure 4 depicts in a crimped state an example of pattern of a stent cut from a polymeric tube
  • Figures 5A and 5B depict examples of the surface features of an embodiment of a device
  • Figure 6 shows a typical series of OCT images following implant of an embodiment of a device in a porcine model
  • Figure 7 shows the stent diameter at various time points following implant of an embodiment of a device in a porcine model
  • Figure 8 depicts an example of a method used to calculate % stenosis following implant of an embodiment of a device in a porcine model
  • Figure 9 shows the observed % stenosis following implant of an embodiment of a device in a porcine model
  • Figure 10 shows an example of vascular response at 180 days following implant of an embodiment of a device in a porcine model
  • Figure 11 shows the PK results following implant of an embodiment of a device in a porcine model
  • Figure 12A, 12B, and 12C show the degradation of the implant in a porcine model of an embodiment.
  • Figure 13 shows embodiments of compressive radial stress and recoil of
  • BDES drug eluting stent
  • BMS bare metal stent
  • Figure 14 shows embodiments of flexibility, and conformability of BDES vs. BMS
  • Figure 15 shows a plot of a stent diameter over time in a water bath at 37°C in one embodiment
  • Figure 16 shows a plot of M w of stents of Design A and Design B embodiments over time in a water bath at 37°C;
  • Figure 17 shows a plot of strength of stents of Design A and Design B embodiments over time in a water bath at 37°C;
  • Figure 18 shows a stent balloon expanded to about 3.6 mm outer diameter (OD) wherein the stent further self expands within one hour by at least 0.1 mm;
  • Figure 19A and 19B show balloon expanded stents at least maintain the diameter of tubular stents of design A, design B, and design C, embodiments over time (1 month and 6 months, respectively);
  • Figure 20 shows changes in the strength of tubular stents of design A, design B, and design C embodiments over time
  • Figure 21 shows the decrease of molecular weight of stent over one to two years with radial strength sufficient to support a blood vessel for at least 2 months;
  • Figure 22A illustrates a stent scaffold deployed in a block, with a final diameter smaller than block simulating malapposed struts
  • Figure 22B illustrates stent scaffold within 5 - 10 minutes of soaking in water at 37 C, with gaps "resolved", or apposed to the wall and no malapposition present;
  • Figure 23A illustrates a stent scaffold expanded in a mock artery with a 0.3mm mandrel on the side
  • Figure 23B illustrates a stent scaffold with mandrel removed, confirming that a gap is still present
  • Figure 23C illustrates a stent scaffold shows a stent scaffold after 10 minutes of soaking in water at 37 °C
  • Figure 23D illustrates a stent scaffold after 20 minutes of soaking in water where in the stent is apposed against the vessel wall;
  • Figure 24 shows a plot illustrating the first occurrence of fracture after dilating the stent/scaffold to diameters substantially larger than the nominal/labeled stent/scaffold diameter of 3.0mm;
  • Figure 25A depicts a scaffold (another name for a stent) at 3.0mm nominal/labeled diameter
  • Figure 25B depicts a scaffold deployed at nominal and further balloon expanded to about 3.8mm without fracture
  • Figure 25C depicts a scaffold deployed at nominal and further balloon expanded to about 4.0mm without fracture
  • Figure 25D depicts a scaffold deployed at nominal and further balloon expanded to 4.4mm diameter without fracture
  • Figure 25E depicts a scaffold deployed at about nominal and further balloon expanded to about 4.75mm diameter without fracture
  • Figure 25F depicts a scaffold deployed at about nominal or labeled 3.0mm and further balloon expanded to about 5.1 mm diameter without fracture;
  • Figure 26A and 26B depict the DESolveTM Bioresorbable Coronary Stent Scaffold used in the DESolve 1 clinical trial;
  • Figure 27 depicts preclinical optical coherence tomography (OCT) images of the scaffold at different time points
  • FIG 28 schematically depicts the DESolveTM First-in-Man (FIM) study design
  • FIG 29 depicts Intravascular Ultrasound (IVUS) results from the DESolveTM FIM study
  • Figure 30 depicts the methodology of OCT analysis where NIH stands for neointimal hyperplasia
  • Figure 31 is a block diagram illustrating the principal steps of the methods of the present invention in one embodiment
  • Figures 32A and 32B illustrate an exemplary stent structure which may be fabricated using the methods of the present invention
  • Figure 33 illustrates the stent of Figures 32A and 32B in a radially expanded configuration
  • Figure 34 illustrates a stent pattern utilized in an Example of the present application.
  • Figure 35 illustrates a pharmacokinetic release profile of novolimus from a stent demonstrating that over 85% of the drug released in one month and that a therapeutic tissue drug concentration of 0.5 ng/mg at 90 days.
  • Figure 36 shows a percent diameter stenosis of the novolimus-stent treated blood vessel measured by quantitative coronary angiography (QCA) over two years.
  • QCA quantitative coronary angiography
  • Figure 37 provides optical coherence tomography (OCT) images of of the novolimus- stent treated blood vessel measured by quantitative coronary angiography (QCA) over two years.
  • OCT optical coherence tomography
  • Figure 38 is a graph of the external scaffold area luminal areas derived from the OCT images of Fig. 37.
  • Figure 39 and 40 show a histopathology analysis of alcain blue stained the novolimus-stent treated blood vessel.
  • Fig. 39 shows slides at 28 days, six months, and two years.
  • Fig. 40 shows slides at nine months.
  • Figure 41 shows 6m diabetes subset QCA outcomes.
  • Figure 44 shows vessel, scaffold, and lumen areas and volumes.
  • Figure 45 shows the distribution of NIH obstruction.
  • Figure 47 is a series of IVUS/OCT images which provide a lumen area comparison analysis
  • Figure 48 provides a graphical lumen area comparison analysis.
  • Table 29 provides an incomplete scaffold apposition (ISA) analysis.
  • Figure 49 and 50 provide an NIH quantification by OCT.
  • Figure 51 and 52 provide an NIH thickness and distribution analysis.
  • Figure 53 and 54 provide a strut coverage (safety surrogate) analysis.
  • Figures 55 and 55A depicts an example of a stent pattern for a peripheral stent having a plurality of rings interconnected by flexible links.
  • Figure 56 show a histopathology analysis of the stent of FIG. 55 at one month, six months and fourteen months.
  • Figure 57 shows micro CT images of the implants at of the stent of FIG. 55 at one month, six months and fourteen months.
  • Figure 58 shows OCT images of the implants at of the stent of FIG. 55 at one month, three months, six months, nine months and twelve months.
  • Figure 59 shows the percent area of stenosis of the implants of the stent of FIG. 55.
  • Figure 60 depicts an example of a stent pattern for a peripheral stent having a plurality of rings interconnected by flexible links.
  • Figure 61 depicts another example of a stent pattern for a peripheral stent having a plurality of rings interconnected by flexible links.
  • the stent prostheses may be formed from one or more amorphous, semi-crystalline, or crystalline biodegradable polymers.
  • the polymers are modified or treated to introduce a desired degree of crystallinity.
  • introducing crystallinity into the polymer increases the strength of the polymer so that it is suitable for use as an endoprosthesis and in some cases without substantially lengthening the period of
  • the polymeric material is treated to achieve a desired degree of crystallinity. In other embodiments, the polymeric material is treated to control crystallinity.
  • a biodegradable implantable device comprising a body comprising a material which comprises a biodegradable copolymer or polymer blend or mixture. It is appreciated that any copolymer or polymer blends or mixture described herein can be formed from one, two, three, four or more different monomers or polymers, where each of the monomers or polymers comprising the copolymer or the polymer can be in any amount (e.g., about 0.1% to about 99.9%, or about 0.5% to about 99.5%, or about 1% to about 99%, or about 2% to about 98%, by weight or molarity).
  • the substantially amorphous or semi-crystalline polymeric material or the tubular body formed there from can be modified to control crystallinity (e.g., degree of crystallinity) of the polymeric material.
  • the substantially amorphous or semi- crystalline polymeric material or the tubular body formed therefrom undergoes a
  • biodegradable endoprostheses e.g., stents
  • biodegradable endoprostheses comprising a tubular body formed at least partially from a substantially amorphous, biodegradable polymer
  • the biodegradable endoprostheses are comprised of a material which comprises a biodegradable polymer, or the biodegradable endoprostheses comprise a tubular body comprised of a material which comprises a biodegradable polymer, wherein the material or the polymer is substantially amorphous or semi-crystalline prior to a modification (or treatment), and crystallinity (e.g., degree of crystallinity) of the material or the polymer increases after the material, the polymer, the tubular body, or the endoprosthesis undergoes the modification.
  • crystallinity e.g., degree of crystallinity
  • the crystallinity increases by about 1% to about 40%, or by about 5% to about to about 35%, or by about 10% to about 30, or by about 10% to about 25%, of the original crystallinity prior to modification.
  • the crystallinity after treatment (modification) is less than about 40%, or less than about 35%, or less than about 30%, or less than about 25%.
  • the substantially amorphous polymeric material or semi-crystalline material can decrease the period of degradation of the endoprosthesis or the tubular body to, e.g., less than about four years, or less than about three years, or less than about two years, or less than about one year, or less than about nine months, or less than about six months, or shorter.
  • amorphous biodegradable polymers having less than 10% crystallinity can degrade faster than crystalline polymers but are weaker than crystalline polymers and hence are not typically suitable for vascular implants, such as stents, which need sufficient strength to provide support to the blood vessel.
  • the present invention provides for the modification of polymeric materials to make them suitable for use as biodegradable stents and other endoprostheses.
  • Materials suitable for modification according to the present invention include but are not limited to poly-DL-Lactide, polylactide-co-glycolactide; polylactide-co-polycaprolactone, poly (L-lactide-co-trimethylene carbonate), polytrimethylene carbonate and copolymers; polyhydroxybutyrate and copolymers; polyhydroxyvalerate and copolymers, poly orthoesters and copolymers, poly anhydrides and copolymers, polyiminocarbonates and copolymers and the like.
  • An exemplary stent is made from amorphous material of a copolymer of 85/15 Poly(L-Lactide- co-Glycolide) and processed to increase crystallinity by at least 20% of original crystallinity, preferably by at least 100%, more preferably by at least 1000% of original crystallinity.
  • the biodegradable stent substantially degrades in less than 2 years, preferable less than 1 year, more preferable less than 9 months.
  • the polymers' crystallinity of the polymeric material after modification or treatment is increased by at least 10% of the original crystallinity of the polymer material, preferably by at least 20% of the original crystallinity of the polymer material, preferably by at least 50% of the original crystallinity of the polymer material, and more preferably by at least 100 % of the original crystallinity of the polymer material.
  • the initial diameter is 0.9-1.5 times the stent deployment diameter, or the stent nominal diameter.
  • the stent nominal diameter is the labeled
  • the stent deployment diameter usually is the deployed diameter of the stent at nominal or bigger diameter. In another embodiment, the initial diameter is smaller than the deployed stent diameter or smaller than the labeled stent deployed diameter.
  • the polymeric material prior to a treatment is amorphous. In other embodiments, the polymeric material prior to a treatment is semi-crystalline. In a further embodiment, the polymeric material prior to a treatment is crystalline.
  • the material comprising the body of the device or the biodegradable polymer or copolymer has a crystallinity or percent crystallinity by X-ray diffraction (XRD) or differential scanning calorimetry (DSC), by weight or volume of about 0%, 1%, 2%, 5% or 10% to about 70%; or about 0%, 1%, 2%, 5% or 10% to about 60%; or about 0%, 1%, 2%, 5% or 10% to about 55%; or about 0%, 1%, 2%, 5% or 10% to about 50%; or about 0%, 1%, 2%, 5% or 10% to about 40%; or about 0%, 1%, 2%, 5% or 10% to about 30%; or about 0%, 1%, 2%, 5% or 10% to about 25%; or about 0%, 1%, 2%, 5% or 10% to about 20%.
  • XRD X-ray diffraction
  • DSC differential scanning calorimetry
  • the material e.g., polymeric material
  • the material comprising the body of the device or the biodegradable polymer copolymer has a degree of crystallinity, or % crystallinity by XRD or DSC, of about 5% to about 30%, or about 7% to about 22%, by weight or volume.
  • the amorphous biodegradable polymeric material is processed to increase its crystallinity. Increased crystallinity may increase the strength, storage shelf life, and hydrolytic stability of the polymer stent material.
  • the process initiates and/or enhances crystallinity in the polymeric material by nucleating and/or growing small size spherulite crystals in the material. Since the amorphous regions of the modified polymer in some embodiments are preferentially broken down by hydrolysis or enzymatic degradation in biological environment, the modified amorphous biodegradable polymer in those
  • embodiments has increased crystallinity and increased material strength post processing.
  • the increase in crystallinity can be achieved by modifications described in present invention which include at least one of heating, cooling, pressurizing, addition of additives,
  • the polymer material can be made into a tube by spraying, extrusion, molding, dipping or printing or other process from a selected amorphous copolymer.
  • the amorphous polymer tubing is optionally vacuumed to at least -25 in. Hg, annealed, and quenched to increase crystallinity.
  • the tube is vacuumed at or below 1 torr at ambient temperature to remove water and solvent. It is then annealed by heating to a temperature above the glass transitional temperature but below melting temperature of the polymer material.
  • the annealing temperature is at least 10°C higher than the glass transitional temperature (Tg), more preferably being at least 20°C higher, and still more preferably being at least 30°C higher than the Tg.
  • the annealing temperature is usually at least 5°C below the melting point (Tm), preferably being at least 20°C lower, and more preferably being at least 30°C lower than the Tm of the polymer material.
  • the annealing time is between 1 minute to 10 days, preferably from 30 minutes to 3 hours, and more preferably from 1.5 hours to 2.5 hours.
  • the treatment comprising heating ranges from a fraction of a second to seven days, preferably from 30 seconds to 3 days, more preferably from 1 minute to 24 hours, and most preferably from 2 minutes to 10 hours.
  • the heated (annealed) tube is quenched by fast cooling from the annealing temperature to a temperature at or below ambient temperature over a period from 1 second to 1 hour, preferably 1 minute to 30 minutes, and more preferably 5 minutes to 15 minutes.
  • the annealed tune is quenched by slow cooling from the annealing temperature to at or below ambient temperature within 1 hour to 24 hours, preferably 4 hours to 12 hours, and more preferably 6 hours to 10 hours.
  • the heat treated tube is cooled to a temperature below ambient temperature for a period from 1 minute to 96 hours, more preferably 24 hours to 72 hours, to stabilize the crystals and/or terminate crystallization.
  • This annealing and quenching process initiates and promotes nucleation of crystals in the polymer and increases the mechanical strength of the material.
  • the initial annealing temperature and the cooling rate can be controlled to optimize the size of the crystals and strength of the material.
  • the unannealed and/or annealed tube is exposed to ebeam or gamma radiation, with single or multiple doses of radiation ranging from 5 kGy to 100 kGy, more preferably from 10 kGy to 50 kGy.
  • the biodegradable polymeric stent material can have increased crystallinity by cross-linking such as exposure to radiation such as gamma or ebeam.
  • the cumulative radiation dose can range from 1 kGy to 1000 KGy, preferably 5 to 100 KGy, more preferably 10 to 30 KGy.
  • Crystallinity (e.g., degree of crystallinity) of the material (e.g., polymeric material) comprising a polymeric material (e.g., a tube) can be controlled by exposure of the polymeric article to carbon dioxide gas or liquid, e.g., under conditions used for controlling solvents and monomers as described herein.
  • degree of crystallinity of the polymeric material comprising the polymeric article is relatively low, exposure of the polymeric material to carbon dioxide gas or liquid can control crystallinity by decrease or increase the degree of crystallinity.
  • the degree of crystallinity of the polymeric material is relatively high, exposure of the polymeric article to carbon dioxide gas or liquid can potentially decrease the degree of crystallinity.
  • biodegradable implantable devices comprising a body (e.g., a tubular body) comprising a material which comprises a biodegradable polymer, copolymer, or polymer blend , wherein the material comprising the body, or the biodegradable polymer, copolymer, or polymer blend, or the stent, has a degree of crystallinity of about 0% to about 70%, or of about 0% to about 55%, or of about 0% to about 30%, or of about 0% to about 25%, or of about 5% to about 70%, or of about 5% to about 55%, or of about 5% to about 30%, or of about 5% to about 25%, or of about 10% to about 70%, or of about 10% to about 55%, or of about 10% to about 30%, or of about 10% to about 25%; or of about 15% to about 70%, or of about 15% to about 55%, or of about 15% to about 30%, or of about 15% to about 25%, or of
  • the stent or body or biodegradable material is substantially amorphous. In yet another preferred embodiment, the stent or body or biodegradable material, is substantially amorphous prior to treatment. In yet another preferred embodiment, the stent or body or biodegradable material, is substantially amorphous prior to treatment and substantially amorphous after treatment. In yet another preferred embodiment, the stent or body or biodegradable material, is substantially amorphous prior to treatment and substantially semi-crystalline after treatment. In yet another embodiment, the stent or tubular body or biodegradable material, has crystallinity that is higher prior to treatment than the crystallinity after treatment.
  • the stent or tubular body or biodegradable material has crystallinity that is higher prior to treatment than the crystallinity after treatment wherein the stent or tubular body or biodegradable material, is in an amorphous state prior to said treatment.
  • the stent or tubular body or biodegradable material has crystallinity that is substantially similar prior to treatment to the crystallinity after treatment wherein the stent or tubular body or biodegradable material, is in an amorphous state prior to said treatment.
  • the stent or tubular body or biodegradable material has crystallinity of about 0% to about 50% prior to treatment and has crystallinity of about 0% to about 50% after treatment.
  • the stent or tubular body or biodegradable material has crystallinity of about 0% to about 45% prior to treatment and has crystallinity of about 0% to about 45% after treatment. In yet another embodiment, the stent or tubular body or biodegradable material, has crystallinity of about 0% to about 40% prior to treatment and has crystallinity of about 0% to about 40% after treatment. In yet another embodiment, the stent or tubular body or biodegradable material, has crystallinity of about 0% to about 35% prior to treatment and has crystallinity of about 0% to about 35% after treatment.
  • the stent or tubular body or biodegradable material has crystallinity of about 0% to about 35% prior to treatment and has crystallinity of about 0% to about 35% after treatment. In yet another embodiment, the stent or tubular body or biodegradable material, has crystallinity of about 0% to about 30% treatment and has crystallinity of about 0% to about 30% after treatment. In yet another embodiment, the stent or tubular body or biodegradable material, has crystallinity of about 0% to about 25% prior to treatment and has crystallinity of about 0% to about 25% after treatment.
  • the stent or tubular body or biodegradable material has crystallinity of about 0% to about 20% prior to treatment and has crystallinity of about 0% to about 20% after treatment. In yet another embodiment, the stent or tubular body or biodegradable material, has crystallinity of about 0% to about 15% prior to treatment and has crystallinity of about 0% to about 15% after treatment. In yet another embodiment, the stent or tubular body or biodegradable material, has crystallinity of about 0% to about 25% prior to treatment and has crystallinity of about 0.3% to about 40% after treatment.
  • the stent or tubular body or biodegradable material has crystallinity of about 0% to about 25% prior to treatment and has crystallinity of about 0% to about 20% after treatment.
  • the material comprising the body of the device or the biodegradable polymer, copolymer or the stent has a degree of crystallinity of about 5% to about 30% and a T g of about 35°C to about 70°C.
  • the biodegradable copolymer is a polylactide copolymer, where lactide includes L-lactide, D-lactide and D,L-lactide.
  • the biodegradable polymer or tubular body or prosthesis comprises a poly-l-lactide acid (PLLA) polymer that is substantially amorphous or substantially semi crystalline.
  • the biodegradable polymer or tubular body or prosthesis comprises a PLLA polymer that is substantially amorphous or substantially semi crystalline, wherein the tubular body is substantially randomly oriented, or substantially not oriented, or non uniformly oriented, or not biaxially oriented.
  • the biodegradable polymer is PLLA polymer that is substantially amorphous or substantially semi crystalline, and/or having a % crystallinity ranging from about 0% to about 30%.
  • the biodegradable polymer is PLLA polymer that is substantially amorphous or substantially semi crystalline, and/or having a % crystallinity ranging from about 0% to about 30% after a modification.
  • the biodegradable polymer is PLLA polymer that is substantially amorphous before and after modification.
  • the biodegradable polymer is PLLA polymer that is substantially amorphous before modification and semi crystalline after modification.
  • the biodegradable polymer is PLLA polymer that is substantially semi crystalline before modification and crystalline after modification.
  • the biodegradable polymer is PLLA polymer that is substantially amorphous or substantially semi crystalline and/or having a % crystallinity ranging from about 0% to about 30% after a modification and/or having % elongation or shrinkage of about 10% to about 50% after treatment; or of less than 10% after treatment.
  • the biodegradable polymer is PLLA polymer that is substantially amorphous or substantially semi crystalline, and/or having a % crystallinity ranging from about 0% to about 30% after a modification, and/or having % elongation or shrinkage of about 10% to about 50% after treatment, and/or capable of radial expansion from a crimped state to an expanded state in an aqueous environment at about 37°C.
  • various combinations of the embodiments are included.
  • the treatment(s) of the biodegradable polymeric material controls maintaining crystallinity to be substantially the same.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, or spraying, said biodegradable polymeric material has an initial crystallinity and has a Tg greater than 37°C and the stent prosthesis has a crystallinity (biodegradable stent material) that is substantially the same as the initial crystallinity and at body temperature is radially expandable and has sufficient strength to support a body lumen.
  • the material comprising the body of the device or the biodegradable polymer or copolymer has a crystallinity or percent crystallinity by X-ray diffraction (XRD) or differential scanning calorimetry (DSC), by weight or volume of about 0%, 1%, 2%, 5% or 10% to about 70%; or about 0%, 1%, 2%, 5% or 10% to about 60%; or about 0%, 1%, 2%, 5% or 10% to about 55%; or about 0%, 1%, 2%, 5% or 10% to about 50%; or about 0%, 1%, 2%, 5% or 10% to about 40%; or about 0%, 1%, 2%, 5% or 10% to about 30%; or about 0%, 1%, 2%, 5% or 10% to about 25%; or about 0%, 1%, 2%, 5% or 10% to about 20%.
  • XRD X-ray diffraction
  • DSC differential scanning calorimetry
  • the material e.g., polymeric material
  • the material comprising the body of the device or the biodegradable polymer copolymer has a degree of crystallinity, or % crystallinity by XRD or DSC, of about 5% to about 30%, or about 7% to about 22%, by weight or volume.
  • Examples include treating the tubular body by heating the tubular body after forming to temperature at about Tg or lower than Tg or within 10°C higher than Tg, of the biodegradable polymeric material Tg, for duration ranging from a fraction of a second to 7 days, or 5 seconds to 7 days, preferably from 15 seconds to 1 day, more preferably from 30 seconds to 5 hours, and optionally cooling or quenching after heating to above ambient temperature, ambient temperature or below ambient temperature.
  • the heating can take place once or more than once at various stages of the tubular body or stent prosthesis fabrication.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, or spraying and has been treated by heating the tubular body at about Tg or lower of the biodegradable polymeric material Tg, said biodegradable polymeric material is substantially amorphous after said treatment and has a Tg greater than 37°C and the stent prosthesis at body temperature is radially expandable and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, printing, dipping, or spraying and has been treated by heating the tubular body at about Tg or lower of the biodegradable polymeric material Tg, said biodegradable polymeric material has crystallinity of 10%-60% (or 10%-50% or 10%- 40% or 10% to 30% or 10%-20% or 0%-10% or 0% to 30%) after said treatment and has a Tg greater than 37°C and the stent prosthesis at body temperature is radially expandable and has sufficient strength to support a body lumen.
  • the Tg is greater than 37°C and less than 60°C, preferably greater than 37°C and less than 55°C, more preferably greater than 37°C and less than 45°C, more preferably greater than 35°C and less than 45°C.
  • the degree of crystallinity is controlled in the polymeric material to about 40% or less, or about 35% or less, or about 30% or less, or about 25% or less, or about 20% or less, or about 15% or less, or about 10% or less, or about 8% or less, or about 6% or less, or about 4% or less, or about 2% or less, prior to a modification (or treatment) or after modification.
  • the degree of crystallinity of a polymeric material is about 10% or less prior to a modification.
  • the degree of crystallinity of the polymeric material is controlled such as to increases or decrease by at least about 5%, 10%, 20%, 30%, 40%, 50%, 100%, 150%, 200%, 300%, 400%, 500%, 600%, 700%, 800%, 900% or 1000 % (e.g., of the initial degree of crystallinity or before treatment).
  • the degree of crystallinity of the polymeric material increases by at least about 50%.
  • polymeric material or a tubular body formed therefrom undergoes a modification, the polymeric material has a degree of crystallinity of about 2%, 5% or 10% to about 70%; or about 2%, 5% or 10% to about 60%; or about 2%, 5% or 10% to about 50%; or about 2%, 5% or 10% to about 40%; or about 2%, 5% or 10% to about 30%; or about 2%, 5% or 10% to about 20%.
  • the polymeric material or a tubular body formed therefrom undergoes a modification, the polymeric material has a degree of crystallinity of about 10% to about 40%.
  • the polymer material or tubular body or stent comprises PLLA/PCL (polymer blend or copolymers), wherein the tubular body is substantially oriented, or at least axially oriented, or biaxially oriented, or substantially randomly oriented, or substantially not oriented.
  • the polymer material is PLLA/PCL (polymer blend or copolymers) and an additive of carbon nano tube or fibers are added to it. The amounts of carbon nano tube or fibers ranges from about 0.1% to about 15%.
  • the polymer material comprises
  • PLLA/PCL/PGA polymer blend or copolymers or a mixture of copolymers and polymer blend
  • the amounts of carbon nano tube or fibers ranges from about 0.1% to about 15%.
  • crystallinity of the tubular body after modification ranges from about 10% to about 70% and % elongation ranges from about 10% to about 200%
  • Tg ranges from about 35°C to about 60°C, or a Tg greater than 37°C to about 55°C, or a Tg greater than 37°C to about 45°C, or a Tg greater than 35°C to about 45°C.
  • the material comprising the body of an endoprosthesis (e.g., a stent), or comprising the polymeric article/material (e.g., a polymeric tube) from which the endoprosthesis is formed, has a degree of crystallinity of about 2%, 5% or 10% to about 70%, or about 2%, 5% or 10% to about 60%, or about 2%, 5% or 10% to about 50%, or about 2%, 5% or 10% to about 40%, or about 2%, 5% or 10% to about 30%, or about 2%, 5% or 10% to about 20%, or has a degree of crystallinity of at least about 2%, 5%, 10%, 20%, 25%, 30%, 40%, 50%, 60% or 70%, after the polymeric article and/or the endoprosthesis undergo the modification or treatment.
  • the material e.g., polymeric material
  • the material comprising the polymeric article or the body of the endoprosthesis has a degree of crystallinity of about 5% to about 50%, or about 10% to about 40%, after the polymeric article and/or the endoprosthesis undergo the modification.
  • Increased crystallinity may increase the strength, storage shelf life, and/or hydrolytic stability of the polymeric material or the endoprosthesis formed therefrom.
  • the modification may introduce or enhance crystallinity in the polymeric material by nucleating or growing small spherulite crystals in the polymeric material.
  • Modification of a polymeric material can include longitudinal extension, radial expansion, heating, cooling, pressurizing, vacuuming, addition of an additive, crosslinking, exposure to radiation (e.g., e-beam or gamma radiation), exposure to carbon dioxide gas or liquid, or other modifications described herein, or a combination thereof.
  • biodegradable endoprostheses comprised of a material which comprises a biodegradable polymer, or biodegradable endoprostheses comprising a tubular body comprised of a material which comprises a biodegradable polymer, wherein the material or the polymer is substantially amorphous or semi crystalline or crystalline prior to a modification (or treatment), and crystallinity (e.g., degree of crystallinity) of the material or the polymer increases or decreases after the material, the polymer, the tubular body or the endoprosthesis undergoes the modification.
  • the crystallinity increases or decreases from about 1% to about 30%, in another embodiment, the crystallinity increases from about 1% to about 20%, or from about 1% to about 10% , or no more than 10%.
  • Substantially amorphous or semi-crystalline, biodegradable polymers having a degree of crystallinity of, e.g., about 30% or less, or 20% or less, or 10% or less may degrade faster than crystalline polymers.
  • the present disclosure provides for modifications (or treatments) of polymers, preferably substantially amorphous or semi crystalline polymeric materials to increase crystallinity of biodegradable endoprostheses, e.g., or by increasing the strength of the polymeric material without substantially increasing its degradation time.
  • a biodegradable endoprosthesis (e.g., a stent) formed from a substantially amorphous or semi crystalline polymeric material that has undergone a modification substantially completely degrades in less than about four years, or less than about three years, or less than about two years, or less than about one year, or less than about nine months, or less than about six months.
  • a biodegradable endoprosthesis e.g., a stent
  • a biodegradable polymeric material wherein crystallinity (e.g., degree of crystallinity) of the polymeric material is controlled by increasing or decreasing after the polymeric material undergoes a modification (or treatment).
  • crystallinity e.g., degree of crystallinity
  • the degree of crystallinity of the polymeric material increases or decreases by at least about 10%, 20%, 25%, 30%, 40%, 50%, 75%, 100%, 150%, 200%, 300%, 400%, 500%, 600%, 700%, 800%, 900% or
  • the degree of crystallinity of polymeric material increases by at least about 25% or 50% after the polymeric material undergoes the modification.
  • the biodegradable polymeric stent material has increased crystallinity by using a combination of solvents, with one solvent having solubility parameter within 10% of the solubility parameter of the polymer and the second solvent having solubility parameter at least 10% different than the solubility parameter of the polymer in the solvent.
  • the biodegradable polymer stent material has a crystallinity of greater than 10%, preferably greater than 25%, more preferably greater than 50%.
  • treatment to control crystallinity takes place in such a way as to decrease it after treatment. Examples include decreasing the crystallinity by at least 5%-50%, preferably by at least 10% to 30%.
  • the invention also provides means to improve consistency of strength, recoil or degradation rate of a biodegradable polymer stent material.
  • Another way to control crystallinity of the material e.g., polymeric material
  • an endoprosthesis e.g., a stent
  • the polymeric article/material e.g., a tube
  • one solvent can have a solubility parameter within about 20% (or 10%) of the solubility parameter of the polymeric material
  • the second solvent can have a solubility parameter at least about 20% (or 10%) different than the solubility parameter of the polymeric material in the solvent.
  • the first biodegradable polymer or the material (e.g., polymeric material) comprising the polymeric article or the body of the device has a degree of crystallinity, or percent crystallinity by X-ray diffraction (XRD) or differential scanning calorimetry (DSC), of about 20%, 15%, 10% or 5% or less by weight or volume before the polymeric article or the device undergoes a treatment (e.g., heating or exposure to radiation), and the degree of crystallinity, or % crystallinity by XRD or DSC, of the first biodegradable polymer or the material (e.g., polymeric material) comprising the polymeric article or the body of the device increases by at least about 10%, 20%, 30%, 40%, 50%, 100%, 200%, 300%, 400% or 500% after the polymeric article or the device undergoes the treatment.
  • XRD X-ray diffraction
  • DSC differential scanning calorimetry
  • the first biodegradable polymer or the material (e.g., polymeric material) comprising the polymeric article or the body of the device has a degree of crystallinity, or % crystallinity by XRD or DSC, of about 15% or less by weight or volume before the polymeric article or the device undergoes a treatment (e.g., heating or exposure to radiation), and the degree of crystallinity, or % crystallinity by XRD or DSC, of the first biodegradable polymer or the material (e.g., polymeric material) comprising the polymeric article or the body of the device increases by at least about 20% after the polymeric article or the device undergoes the treatment.
  • a treatment e.g., heating or exposure to radiation
  • the first biodegradable polymer or the material (e.g., polymeric material) comprising the polymeric article or the body of the device has a degree of crystallinity, or % crystallinity by XRD or DSC, of about 20%, 15%, 10% or 5% or less by weight or volume before the polymeric article or the device undergoes a treatment (e.g., heating or exposure to radiation), and the first biodegradable polymer or the material (e.g., polymeric material) comprising the polymeric article or the body of the device has a degree of crystallinity, or % crystallinity by XRD or DSC, by weight or volume of about 2%, 5% or 10% to about 70%, or about 2%, 5% or 10% to about 60%, or about 2%, 5% or 10% to about 50%, or about 2%, 5% or 10% to about 40%, or about 2%, 5% or 10% to about 30%, or about 2%, 5% or 10% to about 20%, after the polymeric article or the device undergoe a treatment
  • the first biodegradable polymer or the material (e.g., polymeric material) comprising the polymeric article or the body of the device has a degree of crystallinity, or % crystallinity by XRD or DSC, of about 15% or less by weight or volume before the polymeric article or the device undergoes a treatment (e.g., heating or exposure to radiation), and the first biodegradable polymer or the material (e.g., polymeric material) comprising the polymeric article or the body of the device has a degree of crystallinity, or % crystallinity by XRD or DSC, of about 10% to about 50% by weight or volume after the polymeric article or the device undergoes the treatment.
  • a treatment e.g., heating or exposure to radiation
  • the first biodegradable polymer or the material (e.g., polymeric material) comprising the polymeric article or the body of the device has a degree of crystallinity, or % crystallinity by XRD or DSC, of about 15% or less, or about 10% or less, by weight or volume before the polymeric article or the device is exposed to radiation (e.g., e-beam or gamma radiation), and the first biodegradable polymer or the material (e.g., polymeric material) comprising the polymeric article or the body of the device has a degree of crystallinity, or % crystallinity by XRD or DSC, of about 10% to about 40%, or about 10% to about 30%, or about 10% to about 20%, by weight or volume after the polymeric article or the device is exposed to the radiation.
  • radiation e.g., e-beam or gamma radiation
  • the first biodegradable polymer or the material (e.g., polymeric material) comprising the polymeric article or the body of the device has a degree of crystallinity, or % crystallinity by XRD or DSC, of about 10% or less by weight or volume before the polymeric article or the device is exposed to radiation (e.g., e-beam or gamma radiation), and the first biodegradable polymer or the material (e.g., polymeric material) comprising the polymeric article or the body of the device has a degree of crystallinity, or % crystallinity by XRD or DSC, of about 10% to about 30% by weight or volume after the polymeric article or the device is exposed to the radiation.
  • radiation e.g., e-beam or gamma radiation
  • the first biodegradable polymer or the material (e.g., polymeric material) comprising the polymeric article has a degree of crystallinity, or % crystallinity by XRD or DSC, of about 15% or less, or about 10% or less, by weight or volume before the device is formed from the polymeric article (e.g., by laser or mechanical cutting), and the first biodegradable polymer or the material (e.g., polymeric material) comprising the body of the device has a degree of crystallinity, or % crystallinity by XRD or DSC, of about 10% to about 40%, or about 10% to about 30%, or about 10% to about 20%, by weight or volume after the device undergoes a treatment (e.g., heating or exposure to radiation).
  • a treatment e.g., heating or exposure to radiation
  • the first biodegradable polymer or the material (e.g., polymeric material) comprising the polymeric article has a degree of crystallinity, or % crystallinity by XRD or DSC, of about 10% or less by weight or volume before the device is formed from the polymeric article (e.g., by laser or mechanical cutting), and the first biodegradable polymer or the material (e.g., polymeric material) comprising the body of the device has a degree of crystallinity, or % crystallinity by XRD or DSC, of about 10% to about 30% by weight or volume after the device undergoes a treatment (e.g., heating or exposure to radiation).
  • a treatment e.g., heating or exposure to radiation
  • the first biodegradable polymer or the material (e.g., polymeric material) comprising the polymeric article or the body of the device has a degree of crystallinity, or % crystallinity by XRD or DSC, by weight or volume of about 2%, 5% or 10% to about 70%, or about 2%, 5% or 10% to about 60%, or about 2%, 5% or 10% to about 55%, or about 2%, 5% or 10% to about 50%, or about 2%, 5% or 10% to about 40%, or about 2%, 5% or 10% to about 30%, or about 2%, 5% or 10% to about 25%, or about 2%, 5% or
  • the first biodegradable polymer or the material (e.g., polymeric material) comprising the polymeric article or the body of the device has a degree of crystallinity, or % crystallinity by XRD or DSC, of about 5% to about 30%, or about 10% to about 25%, or about 7% to about 22%, by weight or volume after the polymeric article or the device undergoes a treatment (e.g., heating or exposure to radiation).
  • a treatment e.g., heating or exposure to radiation.
  • the teachings disclosed herein can be applied to make any appropriate implantable device from a polymeric article comprised of a biodegradable polymeric material.
  • the implantable device can be any implantable device described herein, and may have a tubular body (e.g., a stent) or may not have a tubular body.
  • the polymeric article can have any shape, form and dimensions suitable for making the device (e.g., a polymeric tube from which a stent is patterned).
  • methods for fabricating biodegradable prostheses are provided. The preferred methods comprise providing a tubular body having an initial diameter as-formed, or before patterning, or after patterning, where the tubular body comprises a biodegradable polymeric material.
  • the polymeric material comprises one or more polymers, or one or more co-polymers, or a combination thereof. In another embodiment, the polymeric material comprises one or more polymers, or one or more co-polymers, or one or more monomers, or a combination thereof.
  • the polymeric material or the tubular body is treated to control crystallinity preferably to between 1% and 50%, or more preferably to between 1% and 35%.
  • the polymeric material or the tubular body treatment comprises a heat treatment preferably at substantially the initial diameter, preferably when the initial diameter is 1-1.5 times the stent deployment diameter, to a temperature above glass transition temperature of the polymeric material and below its melting point for a period ranging from a fraction of a second to 7 days.
  • the polymeric material or the tubular body in one embodiment may be cooled after heating to a temperature ranging from below ambient temperature to ambient or above temperature over a period ranging from a fraction of a second to 7 days.
  • the polymeric material or the tubular body initial diameter is approximately 1-1.5 times the stent deployment diameter or stent nominal deployment diameter, or stent labeled deployment diameter.
  • the initial diameter is approximately 0.9-1.5 times the stent deployment diameter or stent nominal deployment diameter, or stent labeled deployment diameter.
  • the biodegradable implantable device can be made using any suitable method, such as spraying, dipping, extrusion, molding, injection molding, compression molding or 3-D printing, using, e.g., BFB3000 from Bits From Bytes company (UK), or a combination thereof.
  • the body of the device is formed from a polymeric article made by spraying a solution or mixture containing the biodegradable copolymer or polymer and a solvent onto a structure.
  • the biodegradable stent is fabricated by forming a tubular body using extrusion, molding such as injection molding, dipping, spraying such as spraying a tube or mandrel, printing such as 3D printing.
  • the tubular body in a preferred embodiment is formed first and then patterned into a structure capable of radial expansion from a crimped configuration preferably at body temperature.
  • the tubular body in another preferred embodiment is formed first and then patterned into a structure capable of radial expansion from a crimped configuration preferably at body temperature and preferably without fracture.
  • the tubular body in another preferred embodiment is formed first and then patterned into a structure capable of being crimped from an expanded configuration to a crimped diameter (at temperature about Tg or less than Tg), and at body temperature capable to be expanded from the crimped configuration preferably without fracture.
  • the polymeric material is patterned first and then forms a tubular body/stent capable of radial expansion at body temperature and/or capable to be crimped preferably at temperature about Tg or less than Tg.
  • the tubular body or polymeric material, or the stent has an initial diameter.
  • the initial diameter is 1-1.5 times the stent deployed diameter.
  • the initial diameter is 0.9-1.5 times the stent deployed diameter.
  • the initial diameter is less than the stent deployed diameter.
  • the initial diameter can be the as-formed diameter, or the diameter before patterning, or the diameter after patterning, or the diameter before crimping.
  • an endoprosthesis e.g., a stent
  • a polymeric tube that has a (e.g., inner or outer) diameter substantially equal to or smaller than deployed (e.g., inner or outer) diameter of the endoprosthesis.
  • an endoprosthesis e.g., a stent
  • a polymeric tube that has a (e.g., inner or outer) diameter, either when the tube is formed or after the tube is radially expanded to a second larger diameter, larger than deployed (e.g., inner or outer) diameter of the endoprosthesis.
  • Patterning a stent from a polymeric tube having a (e.g., inner or outer) diameter larger than deployed (e.g., inner or outer) diameter of the stent can impart advantageous characteristics to the stent, such as reducing radially inward recoil of the stent after deployment and/or improved strength.
  • a stent prosthesis or tubular body or polymeric material has initial diameter (or initial transverse dimension), preferably 1-1.5 times deployed diameter (deployed transverse dimension) or deployed nominal diameter (e.g., deployed nominal transverse dimension), where in the initial diameter (or initial transverse dimension) is as-formed diameter (or transverse dimension), before patterning diameter (or transverse dimension), or after patterning diameter (or transverse dimension), or before crimping diameter (or transverse dimension), and wherein the initial diameter (or initial transverse dimension) is greater than crimped diameter (or crimped transverse dimension).
  • a stent or tubular body first self-expands by at least 0.35 of initial diameter or transverse dimension, and then expands to second larger diameter or transverse dimension, which may be the deployed diameter or transverse dimension, preferably by balloon expansion.
  • the stent or tubular body may expand to 1.0 times or more, or 1.1 times or more, or 1.2 times or more, or 1.3 times or more, or 1.4 times or more, or 1.5 times or more the deployed diameter or nominal diameter (or transverse dimension) at body temperature, without fracturing.
  • the stent or tubular body or polymeric material is crimped from an expanded diameter to a crimped configuration, and at body temperature expands to 1.0 times or more, or 1.1 times or more, or 1.2 times or more, or 1.3 times or more, or 1.4 times or more, or 1.5 times or more the deployed diameter or nominal diameter (or transverse dimension), without fracturing.
  • an expandable stent comprising a biodegradable polymeric material having an initial configuration is provided.
  • the expandable stent at body
  • the temperature can be self-expandable from a crimped configuration and further expandable to a second larger configuration.
  • the polymeric material has been treated to control one or more of crystallinity, Tg, or molecular weight.
  • Tg ranges from about 20 °C to about 50 °C.
  • the second configuration is a deployed configuration.
  • the stent expands to the first and second configurations without fracture and has sufficient strength to support a body lumen.
  • the first expanded configuration has a transverse dimention of at least 0.35 times, or at least 0.45 times, or at least 0.55 times, or at least 0.55 times, or at least 0.7 times, or at least 0.8 times, or at least 1 times the transverse dimension of the initial configuration.
  • the stent expands to the first expanded configuration within a period of 24 hours, or 12 hours, or 4 hours, or 2 hours, or 1 hour, or 30 minutes, or 5 minutes or 30 seconds.
  • the stent is balloon expandable to the second expanded configuration without fracture and with sufficient strength to support a body lumen.
  • an expandable stent comprising a biodegradable polymeric material having an initial configuration is provided.
  • the expandable stent at body
  • thermoelectric temperature can be expandable from a crimped configuration to a first expanded
  • the polymeric material is treated to control one or more of crystallinity, Tg, or molecular weight.
  • the expandable stent comprises a substantially continuous tubular body.
  • the stent expands to the first configuration without fracture and has sufficient strength to support a body lumen.
  • the stent has a nominal expanded configuration with a transverse dimension and the first expanded configuration has a transverse dimention that is at least 1 times the transverse dimension of the transverse dimention of the nominal expanded configuration.
  • the first expanded configuration is a deployed configuration.
  • the stent has a nominal expanded configuration with a transverse dimension and the fierst expanded configuration has a transverse dimention that is 1 time, or 1.1 times, or 1.2 times, or 1.3 times, or 1.35 times, or 1.4 times, or 1.45 times, or 1.5 times the transverse dimension of the transverse dimension of the nominal expanded configuration.
  • the body of the biodegradable implantable device is formed from a polymeric article made by:
  • the polymer, copolymers, and/or solvents can be the same or different for the first and second layers.
  • the solution or mixture containing the biodegradable copolymer contains an additional biodegradable polymer or a non-degradable polymer or both. In certain embodiments, the solution or mixture containing the biodegradable copolymer contains one or more biologically active agents, or one or more additives, or both biologically active agent(s) and additive(s).
  • the solution or mixture containing the second biodegradable polymer contains an additional biodegradable polymer or a non-degradable polymer or both.
  • the solution or mixture containing the second biodegradable polymer contains one or more biologically active agents, or one or more additives, or both biologically active agent(s) and additive(s).
  • the biodegradable copolymer contains about 5, 4, 3, 2, 1, 0.5 or 0.1 wt% or less of each of water, solvent(s), monomer(s), low molecular weight oligomer(s) or particulate(s), or a combination thereof, prior to preparation of the solution or mixture containing the biodegradable copolymer, or after spraying of the solution or mixture, or both.
  • the second biodegradable polymer contains about 5, 4, 3, 2, 1, 0.5 or 0.1 wt% or less of each of water, solvent(s), monomer(s), low molecular weight oligomer(s) or particulate(s), or a combination thereof, prior to preparation of the solution or mixture containing the second biodegradable polymer, or after spraying of the solution or mixture, or both.
  • Low content of water, solvent(s), monomer(s), low molecular weight oligomer(s) or particulate(s), or a combination thereof, in a polymeric material can be achieved by methods described herein.
  • biodegradable implantable devices described herein can be made using any suitable method or technique, including without limitation spraying, dipping, extrusion, molding, injection molding, compression molding or 3-D printing, or a combination thereof.
  • Some embodiments of the present disclosure relate to a method of making a biodegradable implantable device comprising a body comprised of a material which comprises a first biodegradable polymer, the method comprising:
  • the polymer solution or mixture is sprayed onto the structure at ambient temperature. In other embodiments, the polymer solution or mixture is sprayed onto the structure at a temperature below or above ambient temperature. In further embodiments, the polymer solution or mixture is sprayed onto the structure in ambient environment. In other embodiments, the polymer solution or mixture is sprayed onto the structure in a substantially inert environment (e.g., in the presence of nitrogen or argon gas). In additional embodiments, the polymer solution or mixture is sprayed onto the structure in an environment having a relative humidity of about 70% or less, or about 60% or less, or about 50% or less, or about 40% or less, or about 30% or less. In certain embodiments, the polymer solution or mixture is sprayed onto the structure in an environment having a relative humidity of about 50% or less.
  • the first biodegradable polymer can be any biodegradable polymer (including homopolymer or copolymer) described herein.
  • the first biodegradable polymer is a polylactide homopolymer or copolymer, wherein lactide includes L-lactide, D- lactide and D,L-lactide.
  • the first biodegradable polymer is a poly(L- lactide) copolymer.
  • the poly(L-lactide) copolymer can comprise L-lactide and one or more other monomers selected from any of the monomers described herein.
  • the biodegradable poly(L-lactide) copolymer comprises L-lactide in at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% by weight or molarity, and each of the one or more other monomers in no more than about 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25% or 30% by weight or molarity.
  • the biodegradable poly(L-lactide) copolymer comprises L-lactide in at least about 90%, 95% or 99% by weight or molarity, and each of the one or more other monomers in no more than about 1%, 5% or 10% by weight or molarity.
  • the first biodegradable polymer is selected from the group consisting of poly(L-lactide), poly(D-lactide), poly(D,L-lactide), polydioxanone, poly(4- hydroxybutyrate), polysalicylate/polysalicylic acid, poly(propylene carbonate), poly(tyrosine carbonate), poly(cellulose acetate butyrate), poly(L-lactide-co-D-lactide), poly(L-lactide-co- D,L-lactide), poly(L-lactide-co-glycolide), poly(L-lactide-co-E-caprolactone), poly(L-lactide- co-dioxanone), poly(L-lactide-co-3-hydroxybutyrate), poly(L-lactide-co-4-hydroxybutyrate), poly(L-lactide-co-4-hydroxyvalerate), poly(L-lactide-co-ethylene carbonate), poly(L-lactide-
  • the first biodegradable polymer is a block or random copolymer of L-lactide and ⁇ -caprolactone in a weight or molar ratio of about 70:30 to about 99.9:0.1, or about 80:20 to about 99.9:0.1, or about 85: 15 to about 99.9:0.1, or about 85: 15 to about 95:5, or about 87: 13 to about 93:7, or about 90: 10.
  • the first biodegradable polymer is a random copolymer of L-lactide and ⁇ -caprolactone in a weight or molar ratio of about 90: 10.
  • the first biodegradable polymer is a block or random copolymer of L-lactide and glycolide in a weight or molar ratio of about 70:30 to about 99.9:0.1, or about 75:25 to about 95:5, or about 80:20 to about 90: 10, or about 82: 18 to about 88: 12, or about 85: 15.
  • the first biodegradable polymer is a random copolymer of L-lactide and glycolide in a weight or molar ratio of about 85: 15.
  • the first solvent can be any solvent (a single solvent or a mixture of solvents) that dissolves to a suitable extent, and is compatible with, the first biodegradable polymer and any additional material (e.g., an additional polymer, a biologically active agent or an additive, or a combination thereof) in the first solution or mixture, and results in suitable characteristics of the polymeric article (e.g., minimal amount of residual solvent after removal of the solvent, if desired).
  • any solvent a single solvent or a mixture of solvents
  • any additional material e.g., an additional polymer, a biologically active agent or an additive, or a combination thereof
  • Non-limiting examples of solvents include hydrocarbon solvents, toluene, xylenes, 1,2-xylene, 1,3-xylene, 1,4-xylene, halogenated hydrocarbon solvents, dichloromethane, chloroform, trichlorofluoromethane, (l,l,l,3,3,3)-hexafluoro-2-propanol, ethers, diethyl ether, methyl iert-butyl ether, tetrahydrofuran, ketones, acetone, esters, ethyl acetate, tert-butyl acetate, alcohols, methanol, ethanol, isopropanol, ie/t-butanol, amines, diethylamine, and mixtures thereof.
  • the first solvent is
  • dichloromethane or tetrahydrofuran, or acetone.
  • concentration of a polymer in a spray solution or mixture may be based on various factors, such as the viscosity of the polymer, the type of solvent and the type of spray equipment used.
  • spray equipments include, but are not limited to, MicroMistTM sprayers from Sono-Tek (New York) and 784S-SS Aseptic sprayers from EFD (Rhode Island).
  • biodegradable polymer in the first solution or mixture is about 0.1 or 1 mg/mL to about 20 mg/mL, or about 0.5 or 1 mg/mL to about 15 mg/mL, or about 1 or 2 mg/mL to about 10 mg/mL, or about 3 mg/mL to about 7 mg/mL, or about 4 mg/mL to about 6 mg/mL.
  • the concentration of the first biodegradable polymer in the first solution or mixture is about 1 mg/mL to about 10 mg/mL, or about 5 mg/mL.
  • the structure onto which the polymer solution or mixture is sprayed has a substantially flat surface or a contour surface, or both.
  • the structure has an irregular surface, or a surface having surface features.
  • the irregular surface, or the surface having surface features, of the structure has one or more protrusions, and/or one or more indentations, where the protrusions and/or the indentations can be arranged in a regular or irregular manner on the surface.
  • the protrusions and/or the indentations on the surface of the structure can be formed as indentations and/or protrusions, respectively, on the corresponding (e.g., inner) surface of the polymeric article spray coated on the structure for any of a variety of purposes.
  • a polymeric article having indentations and/or protrusions on a surface can be used to make a device that has a variable thickness along its length, which can, e.g., increase its longitudinal flexibility.
  • indentations and/or protrusions on a surface of a device can promote endothelialization of the device with the surrounding tissue after implantation of the device.
  • indentations on a surface of a device can contain one or more biologically active agents, or one or more additives, or both.
  • the structure onto which the polymer solution or mixture is sprayed can have any shape, configuration or form suitable for making a polymeric article.
  • the structure is a substantially cylindrical or tubular structure (e.g., a mandrel, rod, tube or balloon), which can be used to make a polymeric article from which, e.g., a single stent, segmented stent, joined stent or overlap stent can be patterned.
  • the structure is a tapered tubular structure (e.g., a tapered mandrel, rod, tube or balloon), which can be used to make a polymeric article from which, e.g., a tapered stent can be patterned.
  • the structure is a substantially Y-shaped cylindrical or tubular structure (e.g., a substantially Y-shaped mandrel, rod or tube), which can be used to make a polymeric article from which, e.g., a bifurcated stent can be patterned.
  • a substantially Y-shaped cylindrical or tubular structure e.g., a substantially Y-shaped mandrel, rod or tube
  • the polymeric article can have any shape, configuration or form suitable for making an implantable device from the polymeric article.
  • the polymeric article is a polymeric sheet.
  • the polymeric article is a polymeric tube.
  • the polymeric tube is substantially concentric. If a stent is patterned from a polymeric tube, a more concentric tube can result in more uniform thickness of struts, crowns and links of the stent.
  • the polymeric tube has a concentricity of about 0.0025 inch (about 64 microns) or less, or about 0.002 inch (about 51 microns) or less, or about 0.0015 inch (about 38 microns) or less, or about 0.001 inch (about 25 microns) or less, or about 0.0005 inch (about 13 microns) or less.
  • the polymeric tube has a percent concentricity of at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99%. In certain embodiments, the polymeric tube has a concentricity of about 0.001 inch (about 25 microns) or less, or a percent concentricity of at least about 90%.
  • a substantially concentric polymeric tube can be made by, e.g., slowly forming a tube thickness by spraying a solution or mixture of relatively low polymer concentration onto a mandrel that is constantly rotating (clockwise and counter-clockwise) and moving axially (back and forth over the length of the mandrel).
  • the first solution or mixture containing the first biodegradable polymer contains an additional biodegradable polymer or a non-degradable polymer, or both.
  • the additional biodegradable polymer can be any biodegradable polymer described herein, and the non-degradable polymer can be any non-degradable polymer described herein.
  • the first solution or mixture contains poly(L-lactide) or a poly(L-lactide) copolymer, and an additional biodegradable polymer or a non-degradable polymer or both.
  • the first solution or mixture contains poly(L-lactide) and poly(£- caprolactone).
  • the first biodegradable polymer, and any optional additional biodegradable polymer and/or any optional non-degradable polymer can be treated prior to preparation of the first solution or mixture to remove substantially residual water, solvent(s), monomer(s), low molecular weight oligomer(s) and/or particulate(s) from the polymer(s).
  • the first biodegradable polymer, and any optional additional biodegradable polymer and/or any optional non-degradable polymer are exposed to an extracting solvent (e.g., an alcohol, such as methanol or ethanol), or to carbon dioxide gas or liquid under elevated pressure (e.g., at least about 500, 600, 700, 800 900 or 1000 psi for carbon dioxide gas, or at least about 500, 1000, 2000, 3000, 4000 or 5000 psi for carbon dioxide liquid) and optionally under a flow of carbon dioxide, e.g., at least about 10, 20, 30, 40 or 50 ccm (cubic centimeter per minute), optionally at reduced or elevated temperature, for a period of time (e.g., at least about 1, 6, 12, 24, 36 or 48 hours) prior to preparation of the first solution or mixture containing the polymer(s).
  • an extracting solvent e.g., an alcohol, such as methanol or ethanol
  • carbon dioxide gas or liquid under elevated pressure e.g., at least about 500,
  • the first solution or mixture containing the first biodegradable polymer contains one or more biologically active agents, or one or more additives, or both.
  • the biologically active agent(s) can be any biologically active agent described herein, and the additive(s) can be any additive described herein.
  • the biologically active agent(s) include myolimus or novolimus.
  • Applying a mixture containing two or more substances or materials having significantly different surface tensions can result in phase separation of the substances or materials.
  • the following provides embodiments of ways for minimizing or preventing phase separation of substances or materials.
  • Substances or materials having a substantially similar surface tension are applied. If the substances or materials have significantly different surface tensions, a surfactant can be added to the mixture.
  • Exposure of the polymeric article to heat (in terms of, e.g., temperature and exposure time) is minimized during processing and during any sterilization or storage of the article, and exposure of the device formed from the polymeric article to heat is minimized during processing, sterilization and storage (e.g., the device is frozen during sterilization with radiation and during storage).
  • the method of making the device comprises:
  • the second biodegradable polymer can be any biodegradable polymer described herein.
  • the second solution or mixture containing the second biodegradable polymer contains an additional biodegradable polymer or a non-degradable polymer, or both.
  • the additional biodegradable polymer can be any biodegradable polymer described herein, and the non-degradable polymer can be any non-degradable polymer described herein.
  • the second biodegradable polymer, and any optional additional biodegradable polymer and/or any optional non-degradable polymer can be treated as described herein, e.g., to remove residual water, solvent(s), monomer(s), low molecular weight oligomer(s) and/or particulate(s) from the polymer(s).
  • the second solution or mixture containing the second biodegradable polymer contains one or more biologically active agents, or one or more additives, or both.
  • the biologically active agent(s) can be any biologically active agent described herein, and the additive(s) can be any additive described herein.
  • the method of making the device can also comprise spraying a third solution or mixture containing a third biodegradable polymer and a third solvent, a fourth solution or mixture containing a fourth biodegradable polymer and a fourth solvent, a fifth solution or mixture containing a fifth biodegradable polymer and a fifth solvent, or additional polymer solution or mixture to form a third layer containing the third biodegradable polymer, a fourth layer containing the fourth biodegradable polymer, a fifth layer containing the fifth biodegradable polymer, or additional polymer layer of the polymeric article, where the first layer, the second layer, the third layer, the fourth layer, the fifth layer, or additional layer can be in any order.
  • the optional third biodegradable polymer, the optional fourth biodegradable polymer and the optional fifth biodegradable polymer can independently be any combination of the third biodegradable polymer and a third solvent, a fourth solution or mixture containing a fourth biodegradable polymer and a fourth solvent, a fifth solution or
  • biodegradable polymer described herein.
  • the optional third solution or mixture containing the third biodegradable polymer, the optional fourth solution or mixture containing the fourth biodegradable polymer, and the optional fifth solution or mixture containing the fifth biodegradable polymer can each optionally and independently contain an additional biodegradable polymer or a non- degradable polymer, or both.
  • the additional biodegradable polymer and/or the non- degradable polymer optionally in the third solution or mixture, the fourth solution or mixture, and/or the fifth solution or mixture can independently be any biodegradable polymer described herein and any non-degradable polymer described herein.
  • the third biodegradable polymer, the fourth biodegradable polymer, and/or the fifth biodegradable polymer, and any optional additional biodegradable polymer and/or any optional non-degradable polymer can be treated as described herein, e.g., to remove residual water, solvent(s), monomer(s), low molecular weight oligomer(s) and/or particulate(s) from the polymer(s).
  • the optional third solution or mixture containing the third biodegradable polymer, the optional fourth solution or mixture containing the fourth biodegradable polymer, and the optional fifth solution or mixture containing the fifth biodegradable polymer can each optionally and independently contain one or more biologically active agents, or one or more additives, or both.
  • the biologically active agent(s) and/or the additive(s) optionally in the third solution or mixture, the fourth solution or mixture, and/or the fifth solution or mixture can independently be any biologically active agent described herein and any additive described herein.
  • the method of making the device comprises crosslinking the first biodegradable polymer, the optional second biodegradable polymer, the optional third biodegradable polymer, the optional fourth biodegradable polymer, or the optional fifth biodegradable polymer, or any optional additional biodegradable polymer or any optional non-degradable polymer in the first layer, the optional second layer, the optional third layer, the optional fourth layer, or the optional fifth layer of the polymeric article, or crosslinking any combination of the aforementioned polymers.
  • the polymer(s) are crosslinked by exposure to radiation (e.g., ultraviolet, e-beam or gamma radiation), exposure to heat, use of a degradable or non-degradable crosslinker, or use of a crosslinking agent and an initiator, as described herein.
  • radiation e.g., ultraviolet, e-beam or gamma radiation
  • heat e.g., heat, heat, use of a degradable or non-degradable crosslinker, or use of a crosslinking agent and an initiator, as described herein.
  • the method of making the device can also comprise forming one or more layers comprising a corrodible metal or metal alloy, and optionally a non-corrodible metal or metal alloy, to form the polymeric article.
  • the polymeric article can comprise one or more polymer layers and one or more metal layers in any order. For example, a metal layer, or each of multiple metal layers, or multiple metal layers, can lie between polymer layers of the polymeric article.
  • the one or more metal layers can be applied as a first outer layer, and/or as a second outer layer, of the polymeric article.
  • the one or more metal layers can be applied as a first outer layer, and/or as a second outer layer, of the polymeric tube which correspond to the luminal surface and the abluminal surface of the stent.
  • a metal layer can be applied using any suitable method, e.g., by applying a metal film, foil or tube onto the structure (e.g., a structure having a flat surface and/or a contour surface) or over a polymer layer.
  • a stent can be patterned from the polymeric article comprising one or more polymer layers and one or more metal layers using any suitable method (e.g., laser or mechanical cutting).
  • a metal film, foil or tube having the desired stent pattern can be applied onto a mandrel or over a polymer layer (e.g., a metal tube having the desired stent pattern and a slightly larger diameter than the polymeric article can be crimped onto the polymeric article).
  • the metal layer can be textured or treated, before and/or after being applied onto the structure or over a polymer layer, to form surface roughness, surface irregularities or surface features on one or more surfaces of the metal layer.
  • Surface roughness, surface irregularities and surface features of the metal layer can include, but are not limited to, protrusions, spikes, pillars, ridges, mounds, bumps, textures, scratches, scores, streaks, dents, indentations, recesses, trenches, pores, pits, holes and cavities.
  • Surface roughness, surface irregularities or surface features can be formed on the metal layer, before and/or after the metal layer is applied, by any suitable method, such as microblasting, beadblasting, sandblasting, treatment with a corrosive agent, treatment with an acid or base, treatment with water, chemical etching, physical or mechanical etching, or laser treatment, or a combination thereof.
  • the specific corrodible metal or metal alloy in a metal layer and the thickness of the metal layer can be selected to control characteristics of the device, e.g., strength and degradation. If a non-corrodible metal or metal alloy is used in a metal layer, the specific non-corrodible metal or metal alloy and the amount thereof can be selected to impart desired characteristics (e.g., enhanced strength and/or radiopacity) without unduly prolonging the degradation time of the device.
  • desired characteristics e.g., enhanced strength and/or radiopacity
  • the thickness (e.g., average thickness) of a metal layer is about 100 microns or less, or about 80 microns or less, or about 60 microns or less, or about 50 microns or less, or about 40 microns or less, or about 30 microns or less, or about 20 microns or less, or about 10 microns or less, or about 5 microns or less. In certain embodiments, the thickness (e.g., average thickness) of a metal layer is about 30 microns or less, or about 20 microns or less.
  • the presence of one or more metal layers comprising a corrodible metal or metal alloy, and optionally a non- corrodible metal or metal alloy, in the body of a stent can enhance the strength of the stent and allow the struts, crowns and/or links of the stent to have a smaller thickness and/or a smaller width, thereby decreasing the amount of polymeric material used to make the body.
  • a non-corrodible metal or metal alloy in a metal layer, or as an additive, in the body of the device or in a coating on the device can increase the radiopacity of the device, which may dispense with the use of a radiopaque marker.
  • Non-limiting examples of corrodible metals and metal alloys that can independently comprise any metal layer(s) of the body of the device include cast ductile irons (e.g., 80-55- 06 grade cast ductile iron), corrodible steels (e.g., AISI 1010 steel, AISI 1015 steel, AISI 1430 steel, AISI 5140 steel and AISI 8620 steel), melt-fusible metal alloys, bismuth-tin alloys (e.g., 40% bismuth-60% tin and 58% bismuth-42% tin), bismuth-tin-indium alloys, magnesium alloys, tungsten alloys, zinc alloys, shape-memory metal alloys, and superelastic metal alloys.
  • cast ductile irons e.g. 80-55- 06 grade cast ductile iron
  • corrodible steels e.g., AISI 1010 steel, AISI 1015 steel, AISI 1430 steel, AISI 5
  • non-corrodible metals and metal alloys that can optionally and independently comprise any metal layer(s) include without limitation stainless steels (e.g., 316L stainless steel), cobalt-chromium alloys (e.g., L-605 and MP35N cobalt-chromium alloys), nickel-titanium alloys, gold, palladium, platinum, tantalum, and alloys thereof.
  • stainless steels e.g., 316L stainless steel
  • cobalt-chromium alloys e.g., L-605 and MP35N cobalt-chromium alloys
  • nickel-titanium alloys gold, palladium, platinum, tantalum, and alloys thereof.
  • the polymeric article whether associated with the structure or removed from the structure, can be treated to remove residual water, solvent(s), monomer(s), low molecular weight oligomer(s) and/or particulate(s) from the article.
  • the polymeric article is subjected to reduced pressure or heated at elevated temperature (e.g., at least about 50, 60, 70, 80, 90 or 100 °C), or both, for a period of time (e.g., at least about 0.5, 1, 6, 12, 24, 36 or 48 hours).
  • the polymeric article is exposed to an extracting solvent (e.g., an alcohol, such as methanol or ethanol), or to carbon dioxide gas or liquid under elevated pressure (e.g., at least about 500, 600, 700, 800, 900 or 1000 psi for carbon dioxide gas, or at least about 500, 1000, 2000, 3000, 4000 or 5000 psi for carbon dioxide liquid) and optionally under a flow of carbon dioxide (e.g., at least about 10, 20, 30, 40 or 50 ccm), optionally at reduced or elevated temperature, for a period of time (e.g., at least about 0.5, 1, 6, 12, 24, 36 or 48 hours).
  • an extracting solvent e.g., an alcohol, such as methanol or ethanol
  • carbon dioxide gas or liquid under elevated pressure
  • elevated pressure e.g., at least about 500, 600, 700, 800, 900 or 1000 psi for carbon dioxide gas, or at least about 500, 1000, 2000, 3000, 4000 or 5000 psi for carbon dioxide liquid
  • the material (e.g., polymeric material) comprising the polymeric article or the body of the device, or the material (e.g., polymeric material) comprising each layer of the polymeric article or the body of the device comprises about 5, 4, 3, 2, 1.5, 1, 0.5 or 0.1 wt% or less of each of water, solvent(s), monomer(s), low molecular weight oligomer(s) or particulate(s), or a combination thereof.
  • the material (e.g., polymeric material) comprising the polymeric article or the body of the device, or the material (e.g., polymeric material) comprising each layer of the polymeric article or the body of the device comprises about 2 wt or less of each of water, solvent(s), monomer(s), low molecular weight oligomer(s) or particulate(s), or a combination thereof.
  • the polymeric article can also undergo any of a variety of treatments designed, e.g., to control crystallinity, enhance the strength or toughness of the material (e.g., polymeric material) comprising the article, and/or reduce residual or internal stress in the polymeric article.
  • treatments designed e.g., to control crystallinity, enhance the strength or toughness of the material (e.g., polymeric material) comprising the article, and/or reduce residual or internal stress in the polymeric article.
  • Control of crystallinity (e.g., degree of crystallinity) of the polymeric material can achieve a suitable balance between the radial strength (important for, e.g., support of the treated tubular tissue in the subject) and the toughness (important for, e.g., resistance to cracking and fatigue) of the polymeric material.
  • the polymeric article is removed from the structure prior to undergoing a modification or treatment.
  • the polymeric article can also be deformed (e.g., contracted or expanded) in any direction.
  • Deforming the polymeric article in a direction can increase its strength along that direction (e.g., increase its resistance to force applied in that direction).
  • deforming the polymeric article in a direction can align polymer chains substantially in that direction and can induce crystallization and increase crystallinity of the material (e.g., polymeric material) comprising the polymeric article, or can align amorphous polymer chains substantially in that direction without necessarily inducing crystallization of the amorphous polymeric region or increasing crystallinity of the material (e.g., polymeric material).
  • the polymeric article is expanded in a direction (e.g., longitudinal, circumferential or other direction) while being heated at elevated temperature (e.g., at or above the T g of the polymeric material comprising the polymeric article), and then the expanded polymeric article is cooled to a lower temperature (e.g., below T g ).
  • elevated temperature e.g., at or above the T g of the polymeric material comprising the polymeric article
  • the polymeric article can be longitudinally extended by any suitable method.
  • the polymeric article is a tube
  • a tubular structure whose diameter is slightly less than the inner diameter of the polymeric tube can be placed inside the tube, one end of the tube can be held in place, and force can be applied to the other end of the tube to stretch the polymeric tube while maintaining the diameter of the tube relatively uniform along the length of the tube.
  • the polymeric article can be radially expanded by any suitable method.
  • an expandable pressure vessel can be placed inside the tube and then gas or fluid, optionally heated, can be introduced into the vessel to radially expand the polymeric tube to the desired diameter.
  • the expandable pressure vessel can optionally have heating elements for heating the polymeric tube.
  • An alternative method of radial expansion of the polymeric tube is blow molding.
  • the polymeric tube can be placed inside a molding tube having an inner diameter equal to the desired expanded outer diameter of the polymeric tube.
  • Pressurized inert gas e.g., nitrogen or argon
  • the molding tube can optionally have heating elements for heating the polymeric tube.
  • the polymeric article is longitudinally extended and/or radially expanded, optionally while the polymeric article is heated at elevated temperature (e.g., at or above the T g of the polymeric material comprising the polymeric article) and optionally with cooling of the longitudinally extended and/or radially expanded polymeric article to a lower temperature (e.g., below T g ), which can increase the strength of the polymeric article and can induce or increase orientation of crystals, crystalline regions or polymer chains substantially in the longitudinal direction, the circumferential direction, and/or a biaxial direction.
  • elevated temperature e.g., at or above the T g of the polymeric material comprising the polymeric article
  • a lower temperature e.g., below T g
  • the polymeric article is radially expanded while being heated at elevated temperature (e.g., at or above the T g of the polymeric material comprising the polymeric article) and then the radially expanded polymeric article is cooled to a lower temperature (e.g., below T g ), which can increase the strength of the polymeric article and can induce or increase orientation of crystals, crystalline regions or polymer chains substantially in the circumferential direction or a biaxial direction.
  • the polymeric article is longitudinally extended by at least about 25%, 50%, 75%, 100%, 200%, 300%, 400% or 500% of its initial length, and/or radially expanded by at least about 25%, 50%,
  • the polymeric article is longitudinally extended by at least about 50% of its initial length, or radially expanded by at least about 50% of its initial diameter, or both.
  • the polymeric article is longitudinally extended by at least about 100% of its initial length, or radially expanded by at least about 100% of its initial diameter, or both.
  • the polymeric article can be rotated at a certain rate and for a certain period of time, optionally with heating, to induce circumferentially oriented stress, which can increase the radial strength of the polymeric article and/or impart substantially
  • a mandrel having a polymeric tube formed on it can be rotated at a certain rate and for a certain period of time, optionally with heating.
  • Another treatment that can, e.g., control crystallinity of the material (e.g., polymeric material) comprising the polymeric article is exposure of the polymeric article to radiation (e.g., ionizing radiation, such as e-beam radiation or gamma radiation).
  • Ionizing radiation can be used to control physical characteristics (e.g., control crystallinity or promote crosslinking) of the material (e.g., polymeric material) comprising the polymeric article without necessarily sterilizing the article, or to control physical characteristics of the material and sterilize the polymeric article.
  • the polymeric article is exposed to a single dose or multiple doses of e-beam or gamma radiation at ambient temperature, or below or above ambient temperature, where a dose of radiation is at least about 0.1, 1, 5, 10, 20, 30, 40 or 50 kGray (kGy), or the total dose of radiation is about 1 or 5 kGy to about 100 kGy, or about 5 or 10 kGy to about 60 kGy, or about 10 or 20 kGy to about 50 kGy, or about 20 or 30 kGy to about 40 kGy.
  • a dose of radiation is at least about 0.1, 1, 5, 10, 20, 30, 40 or 50 kGray (kGy)
  • the total dose of radiation is about 1 or 5 kGy to about 100 kGy, or about 5 or 10 kGy to about 60 kGy, or about 10 or 20 kGy to about 50 kGy, or about 20 or 30 kGy to about 40 kGy.
  • the polymeric article is cooled to reduced temperature (e.g., below 0 °C) and then is exposed to a single dose or multiple doses of e-beam or gamma radiation totaling about 10 kGy to about 50 kGy.
  • reduced temperature e.g., below 0 °C
  • the strength and/or toughness of the material(s) (e.g., polymeric material(s)] comprising the implantable device can also be enhanced by incorporation of one or more additives in the polymeric article from which the device is formed, and/or by incorporation of one or more additives in a coating on the device.
  • one or more additives can be incorporated in the polymeric article and/or a coating on the device to reinforce and strengthen the material(s), e.g., polymeric material(s), comprising the polymeric article and/or the coating.
  • fibers, particles or the like comprised of the same polymer or a different biodegradable or non-degradable polymer can be incorporated in the polymeric article and/or a coating on the device to reinforce and strengthen the material(s), e.g., polymeric material(s), comprising the polymeric article and/or the coating.
  • the amount of each of the one or more additives e.g., nanotubes, carbon nanotubes, fullerenes,
  • nanoparticles, nanospheres, nanopowders, nanoclay, zeolites, exfoliates, fibers, whiskers, platelets, monomers, polymers, etc.) incorporated in the polymeric article and/or a coating on the device is about 0.1 or 0.5 wt to about 10 wt , or about 0.1 or 0.5 wt to about 5 wt , or about 0.1, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9 or 10 wt .
  • one or more additives e.g., solvents (e.g., dichloromethane and dimethylsulfoxide), glucosemonoesters, citrate esters, adipate esters, epoxidized soy oil, acetyl-tri-n-butyl citrate (ATBC), buturyl-tri-n-hexyl citrate (BTHC), di-iso-nonyl 1,2-cyclohexanedicarboxylate (DINCH), dioctyl terephthalate (DOTP), monomers (e.g., monomer(s) of the polymer(s) comprising the polymeric article and/or the coating), and polymers (e.g., polyethylene carbonate, polyethylene glycol, polyvinylpyrrolidone, and polydimethylsiloxane), can be incorporated in the polymeric article and/or a coating on the device to plasticize or soften the material(s), e.g., polymeric material
  • solvents e
  • a controlled amount of the solvent e.g., about 0.5 wt to about 5 wt , or about 1 wt to about 3 or 4 wt , of the solvent relative to the weight of the material (e.g., polymeric material) comprising the body of the device or a coating on the device, or relative to the weight of the device
  • the material e.g., polymeric material
  • a controlled amount of the solvent can be incorporated in the body of the device and/or a coating on the device by, e.g., incorporating the solvent in the polymeric article and/or a coating and controlling the parameters of any treatments (e.g., heating, vacuuming and/or exposure to carbon dioxide gas or liquid) that the polymeric article and/or the device undergo.
  • a solvent e.g., dichloromethane or dimethylsulfoxide
  • the weight of the material e.g., polymeric material
  • a coating on the device is incorporated in the body of the device and/or a coating on the device as an additive.
  • the biodegradable implantable device may be able to be formed from the polymeric article when the polymeric article is associated with the structure or removed from the structure.
  • a stent can be patterned from a polymeric tube (e.g., by laser or mechanical cutting) when the tube is either associated with a mandrel or removed from the mandrel.
  • the polymeric article is removed from the structure prior to formation of the device from the polymeric article.
  • the implantable device can be formed from the polymeric article using any suitable method or technique.
  • the device is formed from the polymeric article by cutting the polymeric article with a laser to form a pattern of the device.
  • the heat- affect zone and recasting of the material (e.g., polymeric material) comprising the polymeric article can be minimized by employing a laser having a short pulse duration (e.g., a pulse duration in the nanoseconds or femtoseconds).
  • Non-limiting examples of lasers that can be used to cut the polymeric article include excimer lasers and diode-pumped solid-state lasers operating at a wavelength of about 157 nm to about 351 nm, or at about 193 nm, and femtosecond lasers and ultrafast lasers operating at a wavelength of about 600 nm to about 1000 nm, or at about 800 nm.
  • the implantable device can be any device described herein.
  • the stent can be any stent described herein, and can have any pattern and design suitable for its intended use, including any stent pattern and design described herein.
  • the stent is patterned from a polymeric tube that has a (e.g., inner) diameter substantially equal to an intended deployment (e.g., inner) diameter or the maximum allowable expansion (e.g., inner) diameter of the stent.
  • the stent is patterned from a polymeric tube that has a (e.g., inner) diameter greater than (e.g., at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45% or 50% greater than) an intended deployment (nominal or labeled) (e.g., inner) diameter or the maximum allowable expansion (e.g., inner) diameter of the stent.
  • the stent is patterned from a polymeric tube that has a (e.g., inner) diameter at least about 10% greater than an intended (labeled or nominal) deployment (e.g., inner) diameter or the maximum allowable expansion (e.g., inner) diameter of the stent.
  • a polymeric tube that has a (e.g., inner) diameter at least about 10% greater than an intended (labeled or nominal) deployment (e.g., inner) diameter or the maximum allowable expansion (e.g., inner) diameter of the stent.
  • the stent is patterned from a polymeric tube that has a (e.g., inner) diameter of about 2 mm to about 9 mm, or about 2 mm to about 7 mm, or about 2 mm to about 5 mm, or about 2.5 mm to about 4.5 mm, or about 2.75 mm to about 4.5 mm, or about 3 mm to about 4.5 mm, or about 2.75 mm to about 4 mm, or about 3 mm to about 4 mm, or about 3.3 mm to about 3.8 mm.
  • a (e.g., inner) diameter of about 2 mm to about 9 mm, or about 2 mm to about 7 mm, or about 2 mm to about 5 mm, or about 2.5 mm to about 4.5 mm, or about 2.75 mm to about 4.5 mm, or about 3 mm to about 4.5 mm, or about 2.75 mm to about 4 mm, or about 3 mm to about 4 mm, or about 3.3 mm to about 3.8 mm.
  • the stent is patterned from a polymeric tube that has a (e.g., inner) diameter of about 2.75 mm to about 4.5 mm, or about 2.75 mm to about 4 mm.
  • the diameter (e.g., inner diameter) of the polymeric tube is set by heating the tube at a temperature within about 10 °C or 5 °C of the T g , or at or above the T g , of the material (e.g., polymeric material) comprising the tube, and optionally cooling the tube to a temperature below the T g (e.g., at least about 5, 10, 15 or 20 °C below the T g , or to ambient temperature or below).
  • the method of making the biodegradable implantable device comprises applying a first coating solution or mixture containing a biodegradable polymer or a non-degradable polymer, or both, and a solvent to the device to form a first coating disposed over or adjacent to at least a portion of the device.
  • the biodegradable polymer of the first coating can be any biodegradable polymer described herein, and the non-degradable polymer of the first coating can be any non-degradable polymer described herein.
  • the biodegradable polymer of the first coating is a polylactide homopolymer or copolymer, wherein lactide includes L-lactide, D-lactide and D,L-lactide.
  • the biodegradable polymer of the first coating is a poly(L-lactide) homopolymer or copolymer. In further embodiments, the biodegradable polymer of the first coating is a copolymer of L-lactide and glycolide in a weight or molar ratio of about 70:30 to about 99.9:0.1, or about 75:25 to about 95:5, or about 80:20 to about 90: 10, or about 82: 18 to about 88: 12. In an embodiment, the biodegradable polymer of the first coating is a copolymer of L-lactide and glycolide in a weight or molar ratio of about 85: 15.
  • the solvent of the first coating solution or mixture can be any suitable solvent for applying a polymer as described herein.
  • the solvent is dichloromethane.
  • the concentration of the biodegradable polymer or the non-degradable polymer, or both individually or combined, in the first coating solution or mixture is about 0.1 mg/mL to about 15 mg/mL, or about 0.5 mg/mL to about 10 mg/mL, or about 0.5 mg/mL to about 5 mg/mL, or about 1 mg/mL to about 3 mg/mL.
  • the concentration of the biodegradable polymer or the non-degradable polymer, or both individually or combined, in the first coating solution or mixture is about 1 mg/mL to about 3 mg/mL, or about 2 mg/mL.
  • the first coating solution or mixture contains one or more biologically active agents, or one or more additives, or both.
  • the biologically active agent(s) of the first coating can be any biologically active agent described herein, and the additive(s) of the first coating can be any additive described herein.
  • the biologically active agent(s) of the first coating include myolimus or novolimus.
  • the weight percentage of the biologically active agent(s), individually or combined, relative to the amount of the biologically active agent(s) and the polymer(s) in the first coating solution or mixture is about 10% to about 60%, or about 20% to about 60%, or about 30% to about 60%, or about 30% to about 50%, or about 40% to about 50%.
  • the weight percentage of the biologically active agent(s), individually or combined, relative to the amount of the biologically active agent(s) and the polymer(s) in the first coating solution or mixture is about 30% to about 50%, or about 40%.
  • the method of making the device comprises applying a second coating solution or mixture containing a biodegradable polymer or a non-degradable polymer, or both, and a solvent to the device to form a second coating disposed over or adjacent to at least a portion of the first coating.
  • the second coating solution or mixture can contain one or more biologically active agents, or one or more additives, or both.
  • the method can also comprise applying one or more additional coatings to the device.
  • the biodegradable polymer, the non-degradable polymer, the biologically active agent(s) and the additive(s) of the second coating and any additional coating(s) can independently be any biodegradable polymer described herein, any non-degradable polymer described herein, any biologically active agent described herein, and any additive described herein.
  • the first coating and any additional coating(s) can be applied to the implantable device using any suitable method, e.g., by spraying the respective coating solution or mixture onto the device or dipping the device in the respective coating solution or mixture.
  • the coated device can be treated to incorporate or remove any residual water, solvent(s), monomer(s), low molecular weight oligomer(s) and/or particulate(s) from the coating(s) or the device.
  • the coated device is subjected to reduced or elevated pressure or heated at elevated temperature (e.g., at least about 50, 60, 70, 80, 90 or 100 °C), or both, for a period of time (e.g., at least about 0.5, 1, 6, 12, 24, 36 or 48 hours).
  • the coated device can also be treated to stabilize the coating(s) and prevent their smearing (e.g., upon expansion of the device).
  • the coated device is heated at about 50 °C, 60 °C, 70 °C, 80 °C, 90 °C or 100 °C or above, at ambient pressure or under reduced pressure, for a period of time (e.g., at least about 10 min, 30 min, 1 hr, 4 hr, 8 hr or 12 hr).
  • the coated device is heated at about 60 °C or above, at ambient pressure or under reduced pressure, for at least about 10 min.
  • the coated device can be heated in an inert environment (e.g., under nitrogen, argon or other inert gas).
  • the thickness (e.g., average thickness) of each of the first coating and any additional coating(s) independently is about 20 microns or less, or about 15 microns or less, or about 10 microns or less, or about 5 microns or less, or about 4 microns or less, or about 3 microns or less, or about 2 microns or less, or about 1 micron or less. In certain embodiments,
  • the thickness (e.g., average thickness) of each of the first coating and any additional coating(s) independently is about 10 microns or less, or about 5 microns or less.
  • the thickness (e.g., average thickness) of the first coating is about 5 microns or less, or about 3 microns or less.
  • the body of the implantable device can comprise features in and/or on the body, and/or a coating on the device can comprise features in and/or on the coating, that promote degradation of the body and/or the coating.
  • degradation- promoting features include without limitation openings, pores (including partial pores and through pores), holes (including partial holes and through holes), recesses, pits, cavities, trenches, reservoirs and channels.
  • Such degradation-promoting features can be formed by any of a variety of ways.
  • incorporation of an additive in the polymeric article and/or a coating on the device and subsequent removal of the additive by exposure of the polymeric article and/or the device to a solvent that dissolves the additive but does not substantially dissolve the polymer(s) comprising the polymeric article and/or the coating can form pores in and/or on the body and/or the coating of the device.
  • incorporation of an additive e.g., a blowing agent, a gas, a solvent or water
  • incorporation of an additive e.g., a blowing agent, a gas, a solvent or water
  • an additive e.g., a blowing agent, a gas, a solvent or water
  • incorporation of an additive e.g., a substance having a relatively low molecular weight of about 2,000 daltons or less
  • incorporation of an additive can form pores in and/or on the body and/or the coating of the device.
  • an additive e.g., a blowing agent
  • a certain amount of an additive e.g., about 4-10 wt , or about 5 wt , of carbon nanotubes
  • an additive can be incorporated in the polymeric article and/or a coating on the device to form pores in and/or on the body and/or the coating of the device.
  • the device can undergo any of a variety of treatments designed, e.g., to control or reduce residual or internal stress in the device and/or to control crystallinity and/or control or enhance the strength or toughness of the material(s), e.g., polymeric material(s), comprising the body of the device and/or a coating on the device.
  • the device undergoes one or more cycles of heating and cooling to anneal the material(s), e.g., polymeric material(s).
  • the device is heated at a temperature equal to or greater than the T g of the first biodegradable polymer or the material (e.g., polymeric material) comprising the body of the device for a period of time (e.g., at least about 0.1, 0.25, 0.5, 1, 4, 8, 12 or 24 hours), and then quickly or slowly cooled to a lower temperature (e.g., at least about 10 °C, 20 °C, 30 °C, 40 °C or 50 °C below the T g , or to ambient temperature or below) over a period of time (e.g., about 10 sec, 30 sec, 1 min, 10 min, 30 min, 1 hr, 4 hr, 8 hr or 12 hr).
  • a period of time e.g., at least about 10 sec, 30 sec, 1 min, 10 min, 30 min, 1 hr, 4 hr, 8 hr or 12 hr.
  • the device is heated at a temperature above the T g and below the T m of the first biodegradable polymer or the material (e.g., polymeric material) comprising the body of the device for a period of time (e.g., at least about 0.1, 0.25, 0.5, 1, 4, 8, 12 or 24 hours), and then quickly or slowly cooled to a lower temperature (e.g., at least about 10 °C, 20 °C, 30 °C, 40 °C or 50 °C below the T g , or to ambient temperature or below) over a period of time (e.g., about 10 sec, 30 sec, 1 min, 10 min, 30 min, 1 hr, 4 hr, 8 hr or 12 hr).
  • a period of time e.g., at least about 10 sec, 30 sec, 1 min, 10 min, 30 min, 1 hr, 4 hr, 8 hr or 12 hr.
  • the device is heated at a temperature within the cold crystallization
  • a period of time e.g., at least about 10 sec, 30 sec, 1 min, 10 min, 30 min, 1 hr, 4 hr, 8 hr or 12 hr.
  • the device is heated at a temperature equal to or greater than the T m of the first biodegradable polymer or the material (e.g., polymeric material) comprising the body of the device for a period of time (e.g., at least about 0.1, 0.25, 0.5, 1, 4, 8, 12 or 24 hours) to melt crystalline regions of the first biodegradable polymer or the material (e.g., polymeric material), and then quickly or slowly cooled to a lower temperature (e.g., at least about 10 °C, 20 °C, 30 °C, 40 °C or 50 °C below the T g , or to ambient temperature or below) over a period of time (e.g., about 10 sec, 30 sec, 1 min, 10 min, 30 min, 1 hr, 4 hr, 8 hr or 12 hr).
  • a period of time e.g., at least about 10 sec, 30 sec, 1 min, 10 min, 30 min, 1 hr, 4 hr, 8
  • Another treatment that can, e.g., control crystallinity of the material(s), e.g., polymeric material(s) comprising the body of the device and/or a coating on the device is exposure of the device to radiation (e.g., ionizing radiation, such as e-beam radiation or gamma radiation).
  • Ionizing radiation can be used to control physical characteristics (e.g., control crystallinity or promote crosslinking) of the material(s), e.g., polymeric material(s), comprising the body of the device and/or a coating on the device without necessarily sterilizing the device, or to control physical characteristics of the material(s) and sterilize the device.
  • the device is exposed to a single dose or multiple doses of e- beam or gamma radiation at ambient temperature, or below or above ambient temperature, where a dose of radiation is at least about 0.1, 1, 5, 10, 20, 30, 40 or 50 kGy, or the total dose of radiation is about 1 or 5 kGy to about 100 kGy, or about 5 or 10 kGy to about 60 kGy, or about 10 or 20 kGy to about 50 kGy, or about 20 or 30 kGy to about 40 kGy.
  • the device is cooled to reduced temperature (e.g., below 0 °C) and then is exposed to a single dose or multiple doses of e-beam or gamma radiation totaling about 10 kGy to about 50 kGy, or about 30 kGy.
  • reduced temperature e.g., below 0 °C
  • the device can be rotated at a certain rate and for a certain period of time, optionally with heating, to induce circumferentially oriented stress, which can increase the radial strength of the device and/or impart substantially circumferential or biaxial orientation to the polymeric material comprising the body of the device.
  • a mandrel having a stent associated with it can be rotated at a certain rate and for a certain period of time, optionally with heating.
  • the stent can be crimped to a reduced diameter so that the stent can be delivered through a vessel or passage of a subject.
  • the stent is crimped to an inner diameter of about 0.4mm, 1 mm to about 2 mm, or about 1.2 mm to about 1.6 mm, or about 1.3 mm to about 1.5 mm.
  • the stent is crimped to an inner diameter of about 1.3 mm to about 1.5 mm, or about 1.4 mm.
  • the stent is crimped at ambient temperature, or is crimped at a temperature (crimping temperature) of at least about 30 °C, 35 °C, 40 °C, 45 °C or 50 °C, and the stent crimped at elevated temperature is then cooled to a lower temperature (e.g., at least about 5 °C, 10 °C, 15 °C, 20 °C, 25 °C or 30 °C below the crimping temperature, or to ambient temperature or below).
  • the stent is crimped at about 40 °C or above, and the crimped stent is then cooled to a temperature at least about 5 °C below the crimping temperature.
  • Radially inward recoil of the stent after it is deployed can be reduced by crimping the stent at a temperature at about the T g or below the T g of the material (e.g., polymeric material) comprising the stent body.
  • the stent is crimped at an elevated temperature that is at about the T g or at least about 1 °C, 5 °C, 10 °C, 15 °C, 20 °C, 25 °C, 30 °C, 35 °C, 40 °C, 45 °C or 50 °C below the T g of the material (e.g., polymeric material) comprising the stent body.
  • the stent is crimped at an elevated temperature that is at least about 5 °C below the T g of the material (e.g., polymeric material) comprising the stent body.
  • the conditions in which the crimped stent is treated and handled can affect cracking, recoil, radial strength and uniformity of radial expansion of the stent.
  • Minimizing exposure of the crimped stent to heat can decrease cracking and recoil and improve radial strength and uniformity of radial expansion.
  • Heat may promote generation of a crimped-state memory and may promote erasure of some amount of the as-cut tube memory (the diameter of the tube used to pattern the stent).
  • cracking and recoil can be decreased and radial strength and uniformity of radial expansion can be improved by exposing the crimped stent to a temperature not exceeding the T g , or at least about 1 °C, 5 °C, 10 °C, 15 °C, 20 °C, 25 °C or 30 °C below the T g , of the material (e.g., polymeric material) comprising the stent body during, e.g., stabilization of the stent in the crimped state, mounting of the crimped stent onto a balloon-catheter, sterilization of the stent delivery system (e.g., with e-beam), and storage.
  • the material e.g., polymeric material
  • the presence of heat may induce crystallization of the polymeric material comprising the stent body over time.
  • Crystallization of the polymeric material may or may not be accompanied by increase in the glass transition temperature of the polymeric material, and may render the polymeric material more brittle. Greater brittleness of the polymeric material may increase cracking of crowns of the stent upon radial expansion of the stent. Crystallization of the polymeric material during storage may also strengthen the crimped-state memory and may weaken the as-cut tube memory of the stent, which may result in less uniform radial expansion of the stent and greater radially inward recoil of the stent after expansion.
  • the stent body can be comprised of a polymeric material that does not crystallize or increase in crystallinity over time and/or in the presence of heat (whether added or not).
  • the stent polymeric material can already be at its maximum % crystallinity prior to storage of the crimped stent, provided that the polymeric material is not too brittle and is sufficiently tough.
  • one or more crystallization-inhibiting additives can be incorporated in the material (e.g., polymeric material) comprising the stent body.
  • the crystallization-inhibiting additive(s) leach out from the stent material after exposure of the stent to physiological conditions.
  • the crimped stent (or stent delivery system) can be stored at reduced temperature (e.g., at about 10 °C, 5 °C, 0 °C, -5 °C, -10 °C or -20 °C or below).
  • the stent can be formed from a polymeric tube comprised of a polymeric material that has a low % crystallinity, so that any increase in crystallinity of the polymeric material during storage of the crimped stent does not result in a final % crystallinity that may adversely affect physical properties of the stent.
  • the crimped stent prior to sterilization the crimped stent is stabilized in the crimped state at about 20°C to about 35°C, or at about 25°C to about 30°C, or at about 30 °C, or at about 30°C to about 35°C, or at about 35°C to about 45°C; for at least about 0.1 hr, lhr, 2hr, 3hr, 4 hr, 8 hr, 12 hr, 16 hr or 24 hr, or longer.
  • the crimped stent can be mounted onto a balloon-catheter to provide a stent delivery system. In certain embodiments, after
  • sterilization e.g., with e-beam
  • the crimped stent, or the stent mounted on a balloon-catheter is stabilized in the crimped state at about 20°C to about the T g of the material (e.g., polymeric material) comprising the body of the stent, or at about 5°C, 10°C, 15°C, 20°C, 25°C or 30°C below the T g , or at about 20°C to about 30°C, or at about 25°C, or at about 30°C to about 35°C, or at about 35°C to about 45°C; for at least about 0.1 hr, lhr, 4hr, 6 hr, 12 hr, 24 hr, 36 hr, 48 hr, 60 hr, 72 hr, 84 hr or 96 hr, or longer. Stabilization of the mounted stent in the crimped state can enhance or control its retention on the balloon or delivery system during
  • Retention of a stent on a balloon-catheter can also be enhanced by forming the inner (luminal) layer of the stent body from, or coating the luminal surface of the stent with, an elastomeric polymeric material, e.g., poly(E-caprolactone), with a relatively high coefficient of friction.
  • an elastomeric polymeric material e.g., poly(E-caprolactone)
  • the relatively high-friction polymeric material can minimize movement of the stent on the balloon.
  • Additional ways for improving retention of a stent on a balloon-catheter include use of a non-permanent adhesive applied to the balloon or the luminal surface of the stent, or both.
  • the adhesive is made from a hydrophobic material that can resist water and lose its tackiness when exposed to water.
  • the adhesive has weak bond force in the shear direction.
  • Raised portions (poofs) formed on the balloon of a balloon-catheter and located at the proximal and distal ends of a stent can maintain the stent on the balloon.
  • Poofs located above the balloon markers of the catheter can be formed on the balloon (see, e.g., Example 1).
  • the balloon poofs can be designed to cap the proximal and distal ends of the stent ( Figure 2).
  • the abluminal surface, the luminal surface and both side surfaces of a crimped stent can be partially or fully covered by a water-soluble or non soluble material that dissolves away after a certain period of time. Coverage of the stent by the water-soluble or non soluble material reduces permeation of water into the body of the stent, which prevents the stent from growing or swelling above the balloon poofs, thereby helping to retain the stent on the balloon.
  • Cap(s) can be placed on the proximal end and/or the distal end of a crimped stent to maintain the stent on a balloon-catheter.
  • a major portion of the cap can be on the balloon- catheter, and a minor portion of the cap can be extended over the stent.
  • the cap covers at most one full crown of the stent, or at most half a crown.
  • the cap can be fitted tightly against the balloon portion of the catheter or be bonded to the catheter.
  • the cap Prior to radial expansion of the stent, the cap maintains the stent on the balloon- catheter.
  • the cap recesses, allowing the stent to expand without hindrance.
  • the cap can be solid and be substantially free of holes, or can be a mesh or have holes.
  • a stent can have locks or lockable elements that help to retain the stent on a balloon-catheter.
  • Figure 3 illustrates a non-limiting example of a stent pattern having lockable elements.
  • the arrow or male on one side of a lockable element engages with the other side or female of an adjacent lockable element and locks in place. Locking of the lockable elements prevents the stent from growing, thereby helping to retain the stent on the balloon.
  • a crimped stent can also be maintained on a balloon-catheter by placing a retractable sheath or sleeve over the stent.
  • the sheath or sleeve can end at or beyond the proximal end and/or the distal end of the stent, or over the stent.
  • the sheath or sleeve can be physically or mechanically retracted from the stent prior to radial expansion of the stent.
  • a stent can be retained on a balloon by placing or crimping a protector stent over the main stent.
  • the protector stent is thin (e.g., about 0.001 inch thick) and has a relatively high degree of crystallinity or a relatively high T g .
  • the protector stent may not grow when exposed to physiological conditions, may not expand evenly or may crack, but the main stent is the stent that is designed to expand substantially evenly and support the treated vessel.
  • the biodegradable stent is retained on a balloon-catheter by any suitable means, including any means described herein, and is configured not to move on the balloon-catheter in at least one longitudinal direction by more than about 5 mm, 4 mm, 3 mm, 2 mm, 1 mm or 0.5 mm, e.g., during delivery of the stent-catheter system through a vessel or passage of a subject.
  • the stent is configured not to move on the balloon-catheter in at least one longitudinal direction by more than about 1 mm.
  • the device e.g., a crimped or uncrimped stent or a stent delivery system
  • a sterilization condition can serve purposes in addition to sterilization of the device, such as controlling crystallinity of the material(s), e.g., polymeric material(s), comprising the device.
  • sterilization conditions include radiation, ionizing radiation, e-beam radiation, gamma radiation, and ethylene oxide gas.
  • the device is exposed to a single dose or multiple doses of e-beam or gamma radiation at ambient temperature, or below or above ambient temperature, where a dose of radiation is at least about 0.1, 1, 5, 10, 20, 30, 40 or 50 kGray (kGy), or the total dose of radiation is about 1 or 5 kGy to about 100 kGy, or about 5 or 10 kGy to about 60 kGy, or about 10 or 20 kGy to about 50 kGy, or about 20 or 30 kGy to about 40 kGy.
  • a dose of radiation is at least about 0.1, 1, 5, 10, 20, 30, 40 or 50 kGray (kGy)
  • the total dose of radiation is about 1 or 5 kGy to about 100 kGy, or about 5 or 10 kGy to about 60 kGy, or about 10 or 20 kGy to about 50 kGy, or about 20 or 30 kGy to about 40 kGy.
  • the device e.g., a crimped or uncrimped stent or a stent delivery system
  • a suitable environment e.g., a sealed bag or a chamber
  • the device is preconditioned for about 1 hr at a relative humidity of at least about 35% and at a temperature of about ambient temperature to about 33 °C.
  • the device is exposed to ethylene oxide gas at a temperature of about ambient temperature to about 33 °C, or at about 25 °C, or between about 20°C to about 40°C; for at least about 4 hr, 8 hr, 12 hr, 16 hr, 24 hr or 30 hr.
  • Sterilization can be conducted in the presence of water chips (e.g., two 4 g water chips) to increase humidity.
  • the device is exposed to ethylene oxide gas at a temperature of about 35 °C to about 50 °C, or about 35 °C to about 45 °C, and at a relative humidity of about 20% to about 80%, or about 30% to about 70%, for at least about 4 hr, 8 hr, 12 hr, 16 hr or 24 hr.
  • a stent can be mounted onto an inflated balloon prior to sterilization, sterilized with ethylene oxide gas at elevated temperature, and then crimped onto the deflated balloon in an aseptic or semi-aseptic environment.
  • the stent-balloon- catheter delivery system can be terminally sterilized by exposure to nitrogen dioxide at about ambient temperature or below for at least about 10, 30, 60, 90 or 120 minutes, using, e.g., a system developed by Noxilizer (Baltimore, Maryland).
  • biodegradable implantable devices such as the stent
  • a polymeric article/material e.g., a polymeric tube
  • a structure e.g., a substantially cylindrical structure
  • a device e.g., a stent
  • a device can be formed from the polymeric article (e.g., by laser or mechanical cutting) while the article is associated with the structure or after the article is removed from the structure.
  • a polymeric article made by dipping, and/or a device formed from such a polymeric article can undergo any one or more of the processing steps and treatments described herein (e.g., longitudinal extension, radial expansion, heating, pressurizing, vacuuming, or exposure to radiation or carbon dioxide, or a combination thereof).
  • Dipping can also be performed to make a polymeric article (e.g., a polymeric tube) comprising two or more polymer layers, where each layer independently contains one or more biodegradable polymers, and optionally one or more non-degradable polymers, one or more biologically active agents, and one or more additives.
  • a structure e.g., a substantially cylindrical structure
  • the coated structure is suitably dried by any of various treatments described herein (e.g., vacuuming, heating, and/or exposure to carbon dioxide gas or liquid).
  • the coated structure is dipped in and then removed from a second solution or mixture containing one or more biodegradable polymers and optional additional material(s) or substance(s), and is suitably dried to form a second polymer layer of the polymeric article.
  • the dipping and drying process can be repeated a desired number of times to form a desired number of polymer layers of the polymeric article.
  • a polymeric article comprising one or more polymer layers and one or more metal layers
  • a metal film, foil or tube comprising a corrodible metal or metal alloy, and optionally a non- corrodible metal or metal alloy
  • a coated structure made by dipping the structure (e.g., a substantially cylindrical structure) in a first solution or mixture containing one or more biodegradable polymers, and optionally one or more non-degradable polymers, one or more biologically active agents, and one or more additives.
  • the metal film, foil or tube can be pre-textured or pre-treated (e.g., by microblasting) prior to its application to form surface roughness on one side of the metal film, foil or tube to enhance its adhesion to the first polymer layer.
  • a second polymer layer can be applied to the metal layer, the other side of the metal film, foil or tube can be pre-textured or pre-treated, or can be treated after its application to the first polymer layer, to form surface roughness on the uncoated side of the metal layer before the structure is dipped in a second solution or mixture containing one or more biodegradable polymers and optional additional material(s) or substance(s).
  • a mandrel whose diameter can be substantially equal to or larger than an intended deployment inner diameter of a stent to be formed from the tube, is dipped in a solution or mixture containing one or more biodegradable polymers and a solvent, and optionally one or more non-degradable polymers, one or more biologically active agents, and one or more additives.
  • concentration of the material(s) in the solution or mixture can be about 1 or 5 mg/mL to about 100 mg/mL, or about 10 or 20 mg/mL to about 50 mg/mL.
  • the mandrel can be dipped in the polymer solution or mixture with or without rotation of the mandrel.
  • the mandrel is dipped in the polymer solution or mixture for a period of time (e.g., at least about 1, 2, 3, 4, 5, 10 or 15 seconds), the mandrel is removed from the polymer solution or mixture at a certain rate that may depend on the desired thickness of the coating/layer or tube (if the tube contains only one polymer layer). More than one cycle of dipping and removal can be performed depending on, e.g., the concentration of the polymer solution or mixture and the desired thickness of the coating/layer or tube.
  • the coated mandrel can be rotated (e.g., held and rotated in a horizontal position) or not rotated.
  • the coated mandrel can undergo vacuuming and/or heating to remove, e.g., any residual solvent(s) and monomer(s).
  • the coated mandrel can also be exposed to carbon dioxide gas or liquid under elevated pressure to remove, e.g., any residual solvent(s), monomer(s), low molecular weight oligomer(s) and/or particulate(s).
  • the thickness and physical characteristics of the coating/layer or tube can be controlled by controlling various parameters, such as the composition and concentration of the polymer solution or mixture, the number of times the mandrel is dipped in the polymer solution or mixture, the duration of each dip, the rate of removal of the mandrel from the polymer solution or mixture, and the conditions and duration of drying after each dip.
  • the suitably dried coated mandrel is dipped in a second solution or mixture containing one or more biodegradable polymers and a solvent, and optionally one or more non-degradable polymers, one or more biologically active agents, and one or more additives.
  • a stent can be patterned from the polymeric tube by, e.g., laser or mechanical cutting while the tube remains on the mandrel or after the tube is removed from the mandrel.
  • Dipping can provide a polymeric tube comprised of a polymeric material that is, or has crystals, crystalline regions or polymer chains that are, substantially randomly oriented or substantially not uniaxially oriented, circumferentially oriented, longitudinally oriented or biaxially oriented, if desired.
  • certain parameters of the dipping process can be controlled, such as the concentration of the polymer solution or mixture, the rate and direction of dipping (e.g., the length of the mandrel is dipped in the polymer solution or mixture horizontally, vertically or at an angle), the rate of rotation, if any, of the mandrel while dipped in the polymer solution or mixture, the rate of removal of the mandrel from the polymer solution or mixture, and the rate of rotation, if any, of the coated mandrel after removal from the polymer solution or mixture.
  • Extrusion is another non-limiting example of a method for making biodegradable implantable devices described herein.
  • one or more biodegradable polymers, and optionally one or more non-degradable polymers, one or more additives, and one or more biologically active agents [if the heating is compatible with the bioactive agent(s)], can be heated and drawn through a die to make a polymeric article (e.g., a polymeric tube).
  • a device e.g., a stent
  • any suitable method e.g., laser or mechanical cutting.
  • tubings can be co-drawn, where each tubing independently contains one or more biodegradable polymers, and optionally one or more non-degradable polymers, one or more additives, and one or more biologically active agents.
  • Drawing the extruded material in a particular direction, optionally at elevated temperature, may induce or increase orientation of the material, or its crystals, crystalline regions or polymer chains, substantially in that direction.
  • the following provides embodiments of ways for making a polymeric article (e.g., a polymeric tube) by extrusion, where the article is comprised of a polymeric material that is, or has crystals, crystalline regions or polymer chains that are, substantially randomly oriented or substantially not uniaxially oriented, circumferentially oriented, longitudinally oriented or biaxially oriented.
  • a polymeric material is extruded at elevated temperature in the presence of a crystallization inhibitor that inhibits crystallization of the polymeric material while the material cools down after it exits the hot extruder nozzle.
  • a polymeric material is extruded at elevated temperature. Immediately after the polymeric material exits the hot extruder nozzle, the polymeric material is rapidly cooled below its crystallization temperature (T c ) or glass transition temperature (T g ), or to ambient temperature or below, to prevent or minimize crystallization of the polymeric material.
  • T c crystallization temperature
  • T g glass transition temperature
  • the resulting polymeric article e.g., polymeric tube
  • a device e.g., a stent
  • a polymeric material is extruded at elevated temperature with a minimal drawing ratio.
  • the resulting polymeric article e.g., polymeric tube
  • T m melting temperature
  • the polymeric material is rapidly cooled below its T c or T g , or to ambient temperature or below, to prevent or minimize crystallization of the polymeric material.
  • the resulting polymeric article can be formed into a device (e.g., a stent).
  • a tubular body e.g., a tube
  • a biodegradable polymeric material having a degree of crystallinity of about 30%, 20%, 15%, 10% or 5% or less
  • spraying dipping, extrusion, molding, injection molding, compression molding or 3- D printing, e.g., by spraying onto a mandrel.
  • the polymeric tube undergoes one or more cycles of heating and cooling (or step-wise heating and then cooling) as described herein, e.g., to increase crystallinity and/or strength of the material (e.g., polymeric material) the tube, and/or to reduce residual or internal stress in the polymeric tube.
  • heating and cooling or step-wise heating and then cooling
  • the degree of crystallinity of the material is about 2%, 5% or 10% to about 70%, or about 2%, 5% or 10% to about 60%, or about 2%, 5% or 10% to about 50%, or about 2%, 5% or 10% to about 40%, or about 2%, 5% or 10% to about 30%, or about 2%, 5% or 10% to about 20%, or increases by at least about 10%, 20%, 25%, 30%, 40%, 50%, 75%, 100%, 150%, 200%, 300%, 400%, 500%, 600%, 700%, 800%, 900% or 1000 %.
  • the heat-treated or radiated polymeric tube is patterned into a stent or other endoprosthesis having a tubular body using any suitable method (e.g., laser or mechanical cutting).
  • a stent or other endoprosthesis can be patterned from a polymeric tube that has not undergone a heat treatment, and the stent or other endoprosthesis can undergo one or more cycles of heating and cooling.
  • both the polymeric tube and the stent or other endoprosthesis can each undergo one or more cycles of heating and cooling.
  • Residual or internal stress may arise during processing of a polymeric article (e.g., a polymeric tube) or a device (e.g., a stent) formed from the polymeric article.
  • a polymeric article e.g., a polymeric tube
  • a device e.g., a stent
  • Residual/internal stress may cause failure (e.g., substantial shortening, shrinkage, warping or the like) of the device if the level of residual/internal stress is high enough to overcome the structural integrity of the device.
  • a polymeric article e.g., a polymeric tube
  • stabilization which can include heating and pre- shrinkage
  • Preparation of a polymeric article (e.g., a polymeric tube) by spraying can decrease the level of residual/internal stress in the article without resorting to stabilization.
  • a method of making a biodegradable endoprosthesis comprising providing a polymeric article (e.g., a tubular body, such as a polymeric tube) composed at least partially of a substantially amorphous or semi-crystalline, biodegradable polymeric material, wherein crystallinity (e.g., degree of crystallinity) of the polymeric material increases after the polymeric article undergoes a modification (or treatment), and wherein the endoprosthesis is formed from the polymeric article.
  • the polymeric material is substantially amorphous or semi crystalline or crystalline prior to the modification, and may or may not be substantially amorphous after the modification.
  • a method of making a biodegradable endoprosthesis comprising providing a polymeric article (e.g., a tubular body, such as a polymeric tube) comprising at least partially of a substantially amorphous or semi-crystalline biodegradable polymeric material, wherein crystallinity (e.g., degree of crystallinity) of the polymeric material decreases after the polymeric material undergoes a treatment, and wherein the endoprosthesis is formed substantially from the polymeric material.
  • the polymeric material is substantially amorphous or semi crystalline or crystalline prior to the modification, and substantially amorphous after the modification.
  • the modification comprises heating, cooling, quenching, pressurizing, vacuuming, crosslinking, addition of an additive, or exposure to radiation or carbon dioxide, or a combination thereof.
  • the polymeric article can have any shape, form and dimensions suitable for making the endoprosthesis (e.g., a patterned polymeric tube stent).
  • a biodegradable endoprosthesis (e.g., a stent) is formed from a polymeric tube, wherein the tube is a substantially continuous cylinder that is substantially free from holes, gaps, voids or other discontinuities.
  • the polymeric tube has an outside diameter of about 2 mm to about 10 mm, or about 2 mm to about 5 mm; a thickness of about 0.01 mm to about 0.5 mm, or about 0.05 mm to about 0.3 mm; and a length of about 2 or 5 mm to about 20, 30, 40 or 80 mm.
  • the polymeric tube has an outside diameter of about 2 mm to about 5 mm, a thickness of about 0.05 mm to about 0.3 mm, and a length of about 5 mm to about 30 mm.
  • an endoprosthesis e.g., a stent
  • a polymeric tube that has a (e.g., inner or outer) diameter substantially equal to or smaller than an intended deployed (e.g., inner or outer) diameter of the endoprosthesis.
  • an endoprosthesis e.g., a stent
  • Patterning a stent from a polymeric tube having a (e.g., inner or outer) diameter larger than an intended deployed (e.g., inner or outer) diameter of the stent can impart advantageous characteristics to the stent, such as reducing radially inward recoil of the stent after deployment.
  • a stent is patterned from a polymeric tube having a (e.g., inner or outer) diameter about 0.85, 0.90, 1.0, 1.05 to about 1.5 times, or about 1.1 to about 1.5 times, or about 1.1 to about 1.3 times, or about 1.15 to about 1.25 times, smaller, same, or larger than an intended deployed (e.g., inner or outer) diameter of the stent.
  • the stent is patterned from a polymeric tube having a (e.g., inner or outer) diameter about 1.1 to about 1.3 times larger than an intended deployed (e.g., inner) diameter of the stent.
  • a stent having a deployed (e.g., inner or outer) diameter of about 2.5, 3 or 3.5 mm can be patterned from a tube having a (e.g., inner or outer) diameter of about 2.75, 3.3 or 3.85 mm (1.1 times larger), or about 3.25, 3.9 or 4.55 mm (1.3 times larger), or some other (e.g., inner or outer) diameter larger than the deployed (e.g., inner or outer) diameter of the stent.
  • the initial diameter of the formed tube is larger than the crimped diameter (e.g., crimped diameter on a delivery system) of the stent prosthesis wherein the tubular body is expanded to a second larger diameter than the initial diameter before patterning or before crimping to the crimped diameter; or wherein the tubular body remains substantially the same diameter before patterning or before crimping to a crimped diameter; or wherein the tubular body is crimped to a smaller diameter than the initial formed diameter before patterning or after patterning.
  • the crimped diameter e.g., crimped diameter on a delivery system
  • the initial diameter of the formed tube is smaller than the crimped diameter of the stent prosthesis wherein the tubular body is expanded to a second larger diameter than the initial diameter before patterning or before crimping; or wherein the tubular body remains substantially the same diameter before patterning or before crimping; or wherein the tubular body is crimped to a smaller diameter than the crimped diameter of the stent prosthesis before patterning or after patterning.
  • the initial diameter of the formed tubular body is greater than 0.015 inches, or greater than 0.050 inches, or greater than 0.092 inches, or greater than 0.120 inches, or greater than 0.150 inches.
  • Stent prosthesis intended deployment diameter is the diameter of the labeled delivery system or balloon catheter.
  • a stent prosthesis when crimped onto a balloon labeled 3.0 mm diameter, the stent prosthesis' intended deployment diameter is 3.0mm.
  • self expandable stent crimped onto a delivery system is labeled a certain deployment diameter.
  • the stent cut from a polymeric tube can be any kind of stent and can have any pattern and design suitable for its intended use, including any kind of stent and any pattern and design described herein. Further, the stent can be a fully self-expandable stent, a balloon- expandable stent, or a stent capable of radially self-expanding prior to balloon expansion to an intended deployed diameter.
  • the degree of crystallinity of the material (e.g., polymeric material) of which an endoprosthesis (e.g., a stent) is comprised may decline as a result of cutting of the polymeric article (e.g., a polymeric tube).
  • a stent is annealed and quenched one or more times after cutting of the polymeric tube, as described herein for annealing and quenching a polymeric article or tube, to increase the degree of crystallinity of the polymeric material (and/or reduce residual/internal stress in the polymeric material or the stent).
  • a heat-treated stent is cooled to a temperature below ambient temperature for a period of about 1 minute to about 96 hours, or about 24 hours to about 72 hours, or about 30 minutes to about 48 hours, or about 1 hour to about 48 hours, or about 1 hour to about 36 hours, or about 1 hour to about 24 hours, or about 1 hour to about 12 hours, or about 4 hours to about 12 hours, to stabilize the stent, and/or stabilize the crystals and/or terminate crystallization in the polymeric material.
  • an unannealed or annealed stent is exposed to ionizing radiation (e.g., e-beam or gamma radiation) at, above or below ambient temperature, with a single dose or multiple doses of radiation totaling about 5 kGy to about 100 kGy, or about 10 kGy to about 50 kGy, or about 10 kGy to about 30 kGy, or about 20 kGy to about 60 kGy, or about 20 kGy to about 40 kGy.
  • ionizing radiation e.g., e-beam or gamma radiation
  • an unannealed or annealed stent is cooled to reduced temperature (e.g., below 0 °C) and then is exposed to a single dose or multiple doses of ionizing radiation (e.g., e-beam or gamma radiation) totaling about 10 kGy to about 50 kGy, or about 30 kGy.
  • reduced temperature e.g., below 0 °C
  • ionizing radiation e.g., e-beam or gamma radiation
  • the body of the device can be formed from a polymeric material made by any suitable method, such as spraying, dipping, extrusion, molding, injection molding, compression molding, or three-dimensional (3-D) printing, or a combination thereof.
  • the body of the device is formed from a polymeric article made by spraying a solution or mixture containing at least the biodegradable copolymer or polymer and at least one solvent onto a structure.
  • a stent can be laser-cut from a polymeric tube made by spraying the polymer solution or mixture onto a mandrel.
  • the polymeric material or tubular body comprising the biodegradable polymer is patterned into a stent using (3-D) printing or laser cut.
  • the polymeric material or tubular body comprising the biodegradable polymer is formed using extrusion or spraying or dipping, or molding, and is patterned into a stent.
  • the stent or body of the device comprises one or more additional polymer layers, and/or one or more metal or metal alloy layers, the additional polymer layer(s) of the polymeric material can be formed by spraying additional solution(s) or mixture(s) containing a biodegradable polymer, and/or the metal layer(s) can be formed by applying metal film(s), foil(s) or tube(s).
  • a polymer solution or mixture can contain one or more additional biodegradable polymers and/or one or more non-degradable polymers, and can also contain one or more biologically active agents and/or one or more additives.
  • the stent or tubular body comprises radiopaque markers. Radiopaque markers can be metallic such as gold, platinum, iridium, bismuth, or combination thereof, or alloys thereof. Radiopaque markers can also be polymeric material. Radiopaque markers can be incorporated in the stent or tubular body when it is being formed or incorporated into the stent or the tubular body after forming.
  • the tubular body or polymeric material or stent may be formed from at least one polymer having desired degradation characteristics where the polymer may be modified to have the desired crystallinity, Tg, recoil, strength, shortening, expansion characteristics, crimping characteristics, crystallinity, Tg, molecular weight, and/or other characteristics in accordance with the methods of the present invention.
  • Polymers include one or more polymers, copolymers, blends, and combination thereof of: Lactides,
  • Glycolides, Caprolactone, Lactides and Glycolides, Lactides and Caprolactones examples poly-DL-Lactide, polylactide-co-glycolactide; polylactide-co-polycaprolactone, poly (L- lactide-co-trimethylene carbonate), polylactide-co-caprolactone, polytrimethylene carbonate and copolymers; polyhydroxybutyrate and copolymers; polyhydroxy valerate and copolymers, poly orthoesters and copolymers, poly anhydrides and copolymers, polyiminocarbonates and copolymers and the like.
  • a particularly preferred polymer comprises a copolymer of L-lactide and glycolide, preferably with a weight ratio of 85% L- lactide to 15% glycolide.
  • the biodegradable copolymer is selected from the group consisting of poly(L-lactide-co-D-lactide), poly(L-lactide-co-D,L-lactide), poly(D-lactide-co- D,L-lactide), poly(lactide-co-glycolide), poly(lactide-co-E-caprolactone), poly(glycolide-co- ⁇ -caprolactone), poly(lactide-co-dioxanone), poly(glycolide-co-dioxanone), poly(lactide-co- trimethylene carbonate), poly(glycolide-co-trimethylene carbonate), poly(lactide-co-ethylene carbonate), poly(glycolide-co-ethylene carbonate), poly(lactide-co-propylene carbonate), poly(glycolide-co-propylene carbonate), poly(lactide-co-2-methyl-2-carboxyl -propylene carbonate
  • the biodegradable copolymer is a block or random copolymer of D- Lactide, DL-Lactide or L-lactide and ⁇ -caprolactone in a weight or molar ratio of about 70:30 to about 99.9:0.1.
  • the biodegradable copolymer is a random copolymer of D- Lactide, DL-Lactide or L-lactide and ⁇ -caprolactone in a weight or molar ratio of about 90: 10, or of about 95:5, or of about 85: 15.
  • the biodegradable copolymer is a block or random copolymer of D- Lactide, DL-Lactide or L-lactide and ⁇ -caprolactone in a weight or molar ratio of about 90: 10, or of about 95:5, or of about 85: 15.
  • the biodegradable copolymer is a block or random copolymer of D- Lactide, DL-Lactide or L-lactide
  • biodegradable copolymer is a random copolymer of D- Lactide, DL-Lactide or L-lactide and glycolic acid in a weight or molar ratio of about 70:30 to about 99.9:0.1.
  • the biodegradable copolymer is a random copolymer of D- Lactide, DL-Lactide or L-lactide and glycolic acid in a weight or molar ratio of about 90: 10, or of about 95:5, or of about 85: 15.
  • the biodegradable copolymer is a block or random copolymer of glycolic acid and ⁇ -caprolactone in a weight or molar ratio of about 70:30 to about 99.9:0.1. In an embodiment, the biodegradable copolymer is a random copolymer of glycolic acid and ⁇ -caprolactone in a weight or molar ratio of about 95:5, or of about 90: 10, or of about 85: 15.
  • the biodegradable copolymer is a block or random copolymer of D-Lactide, DL-Lactide or L-lactide and ⁇ -caprolactone and glycolic acid in a weight or molar ratio of about 70% poly lactide: 30% (glycolic acid and ⁇ -caprolactone) to about 99% Poly Lactide: 0.1% (glycolic acid and ⁇ -caprolactone).
  • the biodegradable copolymer is a random copolymer of D- Lactide, DL-Lactide or L-Lactide and glycolic acid and ⁇ -caprolactone in a weight or molar ratio of about 70:5:25, or of about 85:5: 10, or of about 75:20:5.
  • the stent or the body of the device can comprise one or more additional biodegradable polymers or co-polymers, and/or one or more additional non- degradable polymers.
  • the stent or the body of the device can comprise one or more biodegradable monomers. These monomers can be same or different type from polymer incorporated in the body or stent.
  • the stent or body of the device can comprise one or more biologically active agents, and/or one or more additives such as carbon nano fibers or tubes.
  • the additives can serve any of a variety of functions, including controlling degradation, increasing the strength, increasing elongation, controlling Tg, or/and increasing toughness of the material (e.g., polymeric material) comprising the body of the device (or the material comprising a coating on the body), and/or increasing crystallinity.
  • controlling degradation increasing the strength, increasing elongation, controlling Tg, or/and increasing toughness of the material (e.g., polymeric material) comprising the body of the device (or the material comprising a coating on the body), and/or increasing crystallinity.
  • the body of the device comprises a layer containing the biodegradable copolymer, and one or more additional layers containing a biodegradable polymer or a corrodible metal or metal alloy, wherein the layers can be in any order.
  • the layer containing the biodegradable copolymer and any additional layer(s) containing a biodegradable polymer can contain one or more additional biodegradable polymers and/or one or more non-degradable polymers, and can also contain one or more biologically active agents and/or one or more additives.
  • the body of the device comprises one or more layers of the biodegradable copolymer, and optionally one or more additional layers of a biodegradable polymer same or different or a corrodible metal or metal alloy, wherein the layers can be in any order.
  • the one or more layers of the biodegradable copolymer and optionally the one or more additional layers of a biodegradable polymer (same or different polymer, degradable or non degradable polymer) or a corrodible metal or metal alloy optionally may contain one or more biologically active agents and/or one or more additives in one or more of the layers.
  • the polylactide copolymer is formed from two or more different monomers selected from the group consisting of cc-hydroxyacids, L-lactic acid/L- lactide, D-lactic acid/D-lactide, D,L-lactic acid/D,L-lactide, glycolic acid/glycolide, hydroxyalkanoates, hydroxybutyrates, 3-hydroxybutyrate, 4-hydroxybutyrate,
  • hydroxy valerates 3-hydroxyvalerate, lactones, ⁇ -caprolactone, ⁇ -valerolactone, ⁇ - butyrolactone, ⁇ -propiolactone, 1,4-dioxanone (dioxanone), 1,3-dioxanone, carbonates, trimethylene carbonate, ethylene carbonate, propylene carbonate, 2-methyl-2- carboxylpropylene carbonate, fumarates, propylene fumarate, oxides, ethylene oxide, propylene oxide, anhydrides, orthoesters, DETOSU-l,6HD, DETOSU-t-CDM, ketals and acetals, wherein at least one monomer is L-lactic acid/L-lactide, D-lactic acid/D-lactide or D,L-lactic acid/D,L-lactide.
  • one of the monomers of the polylactide copolymer is L-lactic acid/L-lactide.
  • the polylactide copolymer is selected from the group consisting of poly(L-lactide-co-D-lactide), poly(L-lactide-co-D,L-lactide), poly(D-lactide-co- D,L-lactide), poly(lactide-co-glycolide), poly(lactide-co-E-caprolactone), poly(lactide-co- dioxanone), poly(lactide-co-trimethylene carbonate), poly(lactide-co-ethylene carbonate), poly(lactide-co-propylene carbonate), poly(lactide-co-2-methyl-2-carboxyl-propylene carbonate), poly(lactide-co-ethylene glycol), poly(lactide-co-glycolide-co-E-caprolactone), poly(lactide-co-glycolide-co-trimethylene carbonate), and poly(lactide-co-8-caprolactone-co- trimethylene carbonate
  • the biodegradable implantable device comprising a body comprised of a
  • biodegradable polylactide copolymer can have any features of a biodegradable implantable device comprising a polymeric material or body comprised of a biodegradable polymer (including homopolymer or copolymer) described herein.
  • the biodegradable polymer is selected from the group consisting of polyesters, poly(cc-hydroxyacids), polylactide, polyglycolide, poly(£- caprolactone), polydioxanone, poly(hydroxyalkanoates), poly(hydroxypropionates), poly(3- hydroxypropionate), poly(hydroxybutyrates), poly(3-hydroxybutyrate), poly(4- hydroxybutyrate), poly(hydroxypentanoates), poly(3-hydroxypentanoate),
  • polyiminocarbonates poly(DTH iminocarbonate), poly(bisphenol A iminocarbonate), poly(amino acids), poly(ethyl glutamate), poly(propylene fumarate), polyanhydrides, polyorthoesters, poly(DETOSU-l,6HD), poly(DETOSU-t-CDM), polyurethanes,
  • polyphosphazenes polyamides, nylons, nylon 12, polyoxyethylated castor oil, poly(ethylene glycol), polyvinylpyrrolidone, poly(L-lactide-co-D-lactide), poly(L-lactide-co-D,L-lactide), poly(D-lactide-co-D,L-lactide), poly(lactide-co-glycolide), poly(lactide-co-E-caprolactone), poly(glycolide-co-E-caprolactone), poly(lactide-co-dioxanone), poly(glycolide-co- dioxanone), poly(lactide-co-trimethylene carbonate), poly(glycolide-co-trimethylene carbonate), poly(lactide-co-ethylene carbonate), poly(glycolide-co-ethylene carbonate), poly(lactide-co-propylene carbonate), poly(glycolide-co-propylene carbonate), poly(
  • biodegradable polymer is poly(lactide-co-E-caprolactone).
  • biodegradable polymer is poly(lactide-co-glycolide).
  • biodegradable polymer is poly(lactide-co-glycolide).
  • the biodegradable polymer is poly(lactide-co-E-caprolactone), copolymerized or blended/mixed with poly-glycolide.
  • the biodegradable polymer is poly(lactide-co-E-caprolactone), copolymerized or blended/mixed with poly-glycolide, and/or carbon nano tubes or fibers.
  • the biodegradable polymer is poly(lactide-co-£-caprolactone-co- glycolide) blended, or mixed, with carbon nano fibers or nanotubes.
  • the polymer is at least one of poly lactide, poly glycolide, and poly ⁇ - caprolactone, co-polymerized or mixed with one or more of the other two, and/or blended with carbon nano tubes or fibers.
  • poly lactide poly glycolide
  • poly ⁇ - caprolactone co-polymerized or mixed with one or more of the other two, and/or blended with carbon nano tubes or fibers.
  • the partially self-expandable biodegradable stent comprising a body comprised of a biodegradable polymer can have any features of a biodegradable stent comprising a body comprised of or comprising a biodegradable polymer (including homopolymer or copolymer) described herein.
  • biodegradable stent comprising a body comprised of a material, wherein the material comprises a biodegradable copolymer of L-lactide and ⁇ -caprolactone in a weight or molar ratio of about 70:30 to about 99.9:0.1.
  • the biodegradable copolymer comprises L-lactide and ⁇ -caprolactone in a weight or molar ratio of about 90: 10.
  • the biodegradable copolymer comprises L-lactide and ⁇ -caprolactone in a weight or molar ratio of about 99.9:0.1 to about 70:30, or about 99: 1 to about 80:20, or about 95:5 to about 90: 10, or about 95:5, or about 90: 10, or about 85: 15, or about 80:20, or about 75:25, or about 70:30.
  • L-lactide and ⁇ -caprolactone in a weight or molar ratio of about 99.9:0.1 to about 70:30, or about 99: 1 to about 80:20, or about 95:5 to about 90: 10, or about 95:5, or about 90: 10, or about 85: 15, or about 80:20, or about 75:25, or about 70:30.
  • the biodegradable copolymer comprises L-lactide and ⁇ -caprolactone in a weight or molar ratio of about 99.9:0.1 to about 70:30, or about 99: 1 to about 80:20, or about 95:5 to about 90: 10, or about 95:5, or about 90: 10, or about 85: 15, or about 80:20, or about 75:25, or about 70:30 wherein the polymer (copolymer (or three polymer or more) are substantially amorphous, or semicrystalline, or has orientation, or does not have orientation, or is randomly oriented, or has reduced internal stresses, or has low or no phase separation, or has porosity.
  • the PLLA/polycaprolactone (PCL) has at least one or more additional polymer or copolymer selected from polyglycolic acid (PGA), or/and carbon nanotube or fibers.
  • This additional agent can enhance strength, ductility, or reduce recoil.
  • the biodegradable stent comprising a body comprised of a biodegradable poly(L-lactide-co- ⁇ -caprolactone) copolymer or polymer blend or mixture can have any features of a biodegradable stent comprising a body comprised of a biodegradable polymer (including homopolymer or copolymer) described herein.
  • Non-limiting examples of a biodegradable polymer that can be used to form a biodegradable endoprosthesis or a tubular body thereof, or a polymeric article from which the endoprosthesis or tubular body is formed include polylactide and copolymers thereof, poly(D,L-lactide), poly(lactide-co-glycolide), poly(lactide-co-E-caprolactone), poly(lactide- co-trimethylene carbonate), poly(L-lactide-co-trimethylene carbonate), polytrimethylene carbonate and copolymers thereof, polyhydroxybutyrates and copolymers thereof, polyhydroxyvalerates and copolymers thereof, polyorthoesters and copolymers thereof, polyanhydrides and copolymers thereof, and polyiminocarbonates and copolymers thereof, wherein lactide includes L-lactide, D-lactide and D,L-lactide.
  • the biodegradable endoprosthesis, tubular body or polymeric article is formed from a poly(L-lactide-co-glycolide) copolymer comprising about 80% to about 90% L-lactide and about 10% to about 20% glycolide by weight or molarity.
  • the poly(L-lactide-co-glycolide) copolymer comprises about 85% L-lactide and about 15% glycolide by weight or molarity.
  • the biodegradable endoprosthesis, tubular body or polymeric article is formed from a poly(L-lactide-co-£- caprolactone) copolymer comprising about 85% to about 95% L-lactide and about 5% to about 15% ⁇ -caprolactone by weight or molarity.
  • the poly(L-lactide-co- ⁇ -caprolactone) copolymer comprises about 90% L-lactide and about 10% ⁇ -caprolactone by weight or molarity.
  • the biodegradable copolymer or polymer comprising the body of the device is derived or formed from, or is comprised of, one, two or more different monomers or polymers selected from the group consisting of cc-hydroxyacids, L-lactic acid/L-lactide, D-lactic acid/D-lactide, D,L-lactic acid/D,L-lactide, glycolic acid/glycolide, hydroxyalkanoates, hydroxybutyrates, 3-hydroxybutyrate, 4-hydroxybutyrate,
  • hydroxy valerates 3-hydroxyvalerate, 4-hydroxyvalerate, hydroxybenzoic acids, salicylic acid, lactones, ⁇ -caprolactone, ⁇ -valerolactone, ⁇ -butyrolactone, ⁇ -propiolactone, 1,4- dioxanone (dioxanone), 1,3-dioxanone, carbonates, trimethylene carbonate, ethylene carbonate, propylene carbonate, 2-methyl-2-carboxylpropylene carbonate, tyrosine carbonates, L-tyrosine carbonate, fumarates, propylene fumarate, cellulose esters, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellulose propionate, oxides, ethylene oxide, propylene oxide, anhydrides, orthoesters, DETOSU-l,6HD, DETOSU-t-CDM, ketals, and acetals.
  • one of the monomers or polymers of the biodegradable copolymer or polymer is L-lactic acid/L-lactide.
  • Poly(DETOSU-l,6HD) and poly(DETOSU- t-CDM) are polyorthoesters based on the diketene acetal 3,9-diethylidene-2,4,8,10- tetraoxaspiro[5.5]undecane (DETOSU) and 1,6-hexanediol (1,6-HD) or trans- cyclohexanedimethanol (t-CDM).
  • the biodegradable copolymer or polymer is selected from the group consisting of poly(L-lactide-co-D-lactide), poly(L-lactide-co-D,L-lactide), poly(D- lactide-co-D,L-lactide), poly(lactide-co-glycolide), poly(lactide-co-E-caprolactone), poly(glycolide-co-E-caprolactone), poly(glycolide-co-E-caprolactone), poly(lactide-co-dioxanone), poly(glycolide-co- dioxanone), poly(lactide-co-trimethylene carbonate), poly(glycolide-co-trimethylene carbonate), poly(lactide-co-ethylene carbonate), poly(glycolide-co-ethylene carbonate), poly(lactide-co-propylene carbonate), poly(glycolide-co-propylene carbonate), poly(lactide-co-2-
  • the biodegradable copolymer is a polylactide copolymer, wherein lactide includes L-lactide, D-lactide and D,L-lactide.
  • the biodegradable copolymer is a poly(L-lactide) copolymer.
  • the poly(L-lactide) copolymer can comprise L-lactide and one or more other monomers selected from any of the monomers described herein.
  • the biodegradable copolymer is selected from the group consisting of poly(L-lactide-co-D-lactide), poly(L-lactide-co-D,L-lactide), poly(L- lactide-co-glycolide), poly(L-lactide-co-E-caprolactone), poly(L-lactide-co-dioxanone), poly(L-lactide-co-3-hydroxybutyrate), poly(L-lactide-co-4-hydroxybutyrate), poly(L-lactide- co-4-hydroxyvalerate), poly(L-lactide-co-ethylene carbonate), poly(L-lactide-co-propylene carbonate), poly(L-lactide-co-trimethylene carbonate), and poly(L-lactide-co-cellulose acetate butyrate).
  • the biodegradable poly(L-lactide) copolymer or polymer comprises L-lactide or D-Lactide or DL-Lactide in at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% by weight or molarity, and each of the one or more other monomers or polymers in no more than about 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25% or 30% by weight or molarity.
  • the biodegradable poly(L-lactide) copolymer or polymer comprises L-lactide or D-Lactide or DL-Lactide in at least about 90%, 95% or 99% by weight or molarity, and each of the one or more other monomers or polymers in no more than about 1%, 5% or 10% by weight or molarity.
  • the biodegradable copolymer is poly(lactide-co-£- caprolactone).
  • the biodegradable copolymer is a block or random copolymer of L-Lactide or D-Lactide or DL-Lactide and e-caprolactone in a weight or molar ratio of about 70:30 to about 99.9:0.1, or about 80:20 to about 99: 1, or about 85: 15 to about 99: 1, or about 85: 15 to about 95:5, or about 87: 13 to about 93:7, or about 90: 10.
  • the biodegradable copolymer is a random copolymer of L-lactide or D-Lactide or DL-Lactide and ⁇ -caprolactone in a weight or molar ratio of about 90: 10.
  • the biodegradable polymer is a blend or mixture of L-lactide or D-Lactide or DL-Lactide and ⁇ -caprolactone in a weight or molar ratio of about 70:30 to about 99.9:0.1.
  • the biodegradable copolymer is poly(lactide-co-glycolide).
  • the biodegradable copolymer is a block or random copolymer of L- Lactide or D-Lactide or DL-Lactide and glycolide in a weight or molar ratio of about 70:30 to about 99: 1, or about 75:25 to about 95:5, or about 80:20 to about 90: 10, or about 82: 18 to about 88:12, or about 85: 15.
  • the biodegradable copolymer is a random copolymer of L-lactide or D-Lactide or DL-Lactide and glycolide in a weight or molar ratio of about 85: 15.
  • the body of the device comprises the biodegradable polymer or copolymer, and a second biodegradable polymer or a non-degradable polymer or both.
  • the non-degradable polymer can be any non-degradable polymer described herein.
  • the amount of the non- degradable polymer used can be selected to provide the device with desired characteristics while not extending the degradation time of the device beyond the desired time period.
  • the non degradable polymer is selected from the group consisting of polyacrylates, polymethacrylates, poly(n-butyl methacrylate),
  • the second biodegradable polymer can be any biodegradable polymer or copolymer described herein.
  • the second biodegradable polymer is selected from the group consisting of polyesters, poly(cc-hydroxyacids), polylactide including L-Lactides, D-Lactide, and DL-Lactide, polyglycolide, poly(E-caprolactone), polydioxanone,
  • Poly(DTH iminocarbonate) is a polymer of the desaminotyrosyl- tyrosine hexyl ester (DTH) iminocarbonate.
  • the second biodegradable polymer is a polylactide homopolymer or copolymer, wherein lactide includes L-lactide, D- lactide and D,L-lactide.
  • the second biodegradable polymer is a poly(L-lactide) homopolymer or copolymer.
  • the second biodegradable polymer is selected from the group consisting of poly(L-lactide), poly(D-lactide), poly(D,L-lactide), polyglycolide, poly(£- caprolactone), polydioxanone, poly(L-lactide-co-glycolide), poly(D-lactide-co-glycolide), poly(D,L-lactide-co-glycolide), poly(L-lactide-co-E-caprolactone), poly(D-lactide-co-£- caprolactone), poly(D,L-lactide-co-£-caprolactone), poly(glycolide-co-£-caprolactone), poly(L-lactide-co-trimethylene carbonate), poly(D-lactide-co-trimethylene carbonate), poly(D,L-lactide-co-trimethylene carbonate), poly(glycolide-co-trimethylene carbonate), poly(DTH), poly(D
  • the body of the device, or the material comprising the body of the device comprises a blend of the biodegradable copolymer, and a second biodegradable polymer or a non-degradable polymer or both.
  • the body of the device, or the material comprising the body of the device comprises a blend of a block or random copolymer of L-lactide or D-Lactide or DL-Lactide and ⁇ -caprolactone in a weight or molar ratio of about 70:30 to about 99.9:0.1 and a different block or random copolymer of L- lactide or D-Lactide or DL-Lactide and ⁇ -caprolactone in a weight or molar ratio of about 70:30 to about 99.9:0.1; or a blend of a block or random copolymer of L-lactide or D-Lactide or DL-Lactide and ⁇ -caprolactone in a weight or molar ratio of
  • the body of the device comprises a first layer containing the biodegradable copolymer or polymer, and one, two, three, four or more additional layers , wherein each additional layer contains a biodegradable polymer or a corrodible metal or metal alloy, and wherein the first layer and the additional layer(s) can be in any order.
  • the biodegradable polymer that can compose any additional layer(s) can independently be any biodegradable polymer described herein.
  • the first layer containing the biodegradable copolymer and any additional layer(s) containing a biodegradable polymer can each optionally and independently contain an additional biodegradable polymer or a non- degradable polymer or both.
  • the additional biodegradable polymer that can optionally compose the first layer and any additional layer(s) can independently be any biodegradable polymer described herein, and the non-degradable polymer that can optionally compose the first layer and any additional layer(s) can independently be any non-degradable polymer described herein.
  • Non-limiting examples of corrodible metals and metal alloys that can independently comprise any additional layer(s) of the body of the device include cast ductile irons (e.g., 80- 55-06 grade cast ductile iron), corrodible steels (e.g., AISI 1010 steel, AISI 1015 steel, AISI 1430 steel, AISI 5140 steel and AISI 8620 steel), melt-fusible metal alloys, bismuth-tin alloys (e.g., 40% bismuth-60% tin and 58% bismuth-42% tin), bismuth-tin-indium alloys, magnesium alloys, tungsten alloys, zinc alloys, shape-memory metal alloys, and superelastic metal alloys.
  • cast ductile irons e.g. 80- 55-06 grade cast ductile iron
  • corrodible steels e.g., AISI 1010 steel, AISI 1015 steel, AISI 1430 steel, AISI 5
  • each layer can be selected to have certain characteristics based on its composition so that the device has desired overall characteristics.
  • the material comprising a particular layer can be selected to have certain characteristics (e.g., strength, toughness, ductility, degradation rate, etc.) by containing certain biodegradable polymer(s), and optionally certain nondegradable polymer(s) and certain additive(s), and certain amount thereof, where the characteristics of that material can be substantially similar to or different from the characteristics of the material comprising each of the other layer(s).
  • the body of the device can comprise a middle one or more layer(s) containing a high-strength material, e.g., a high- strength polymer, such as poly(L-lactide) or a copolymer thereof] and inner and outer layer(s) containing a ductile material, e.g., a ductile polymer, such as poly(E-caprolactone), such that the device possesses sufficient strength, flexibility and toughness.
  • a high-strength material e.g., a high- strength polymer, such as poly(L-lactide) or a copolymer thereof
  • inner and outer layer(s) containing a ductile material e.g., a ductile polymer, such as poly(E-caprolactone
  • the biodegradable copolymer, optional second biodegradable polymer, optional additional biodegradable polymer(s), or optional non-degradable polymer(s), or any combination thereof, comprising the body of the device are crosslinked.
  • the polymer(s) are crosslinked by exposure to radiation (e.g., ultraviolet (UV) light, or ionizing radiation, such as e-beam or gamma radiation), exposure to heat, use of a degradable or non-degradable crosslinker, or use of a crosslinking agent and an initiator.
  • radiation e.g., ultraviolet (UV) light, or ionizing radiation, such as e-beam or gamma radiation
  • the degradable or non-degradable crosslinker is selected from the group consisting of diisocyanates, methylene diphenyl diisocyanates,
  • the crosslinking agent is selected from the group consisting of maleic anhydride, l,2-bis(maleimido)ethane, l,4-bis(maleimido)butane, 1,6- bis(maleimido)hexane, l,8-bis(maleimido)diethylene glycol, and tris(2- maleimidoethyl) amine.
  • the initiator is selected from the group consisting of organic peroxides, di-ie/t-butyl peroxide, dicumyl peroxide, benzoyl peroxide, methyl ethyl ketone peroxide, azo compounds, l,l'-azobis(cyclohexanecarbonitrile), and 1 , 1 ' -azobis(isobutyronitrile) .
  • biodegradable implantable device comprising a body comprising a material which comprises a blend of polymers, wherein the blend includes a biodegradable polymer, and an additional biodegradable polymer or a non- degradable polymer or both.
  • the biodegradable polymer and the additional biodegradable polymer can be any biodegradable polymer described herein, and the non-degradable polymer can be any non-degradable polymer described herein.
  • the amount of any non- degradable polymer utilized can be selected to impart desired characteristics (e.g., strength) to the material or the device without prolonging the degradation time of the device over a certain length of time.
  • Embodiments herein relating to a biodegradable implantable device comprising a polymeric material or body comprised of a material which comprises a biodegradable copolymer also relate to a biodegradable implantable device comprising a body comprised of a material which comprises a blend of polymers, where a blend of polymers can substitute for a biodegradable copolymer in such embodiments.
  • the biodegradable implantable device comprises polymeric material or a body comprising a material which comprises Poly(Lactide) such as poly(L- lactide) or a poly(L-lactide) copolymer, and an additional biodegradable polymer or a non- degradable polymer or both.
  • the poly(L-lactide) copolymer can be any poly(L-lactide) copolymer described herein.
  • the material comprising the body of the device comprises poly(L-lactide) and poly(E-caprolactone).
  • the weight percent of poly(L-lactide) or the poly(L-lactide) copolymer in the material comprising the body of the device is at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9%, and the weight percent of each of the additional biodegradable polymer and/or the non-degradable polymer is no more than about 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25% or 30%.
  • the weight percent of poly(L-lactide) or the poly(L-lactide) copolymer in the material comprising the body of the device is at least about 90%, 95% or 99%, and the weight percent of each of the additional biodegradable polymer and/or the non-degradable polymer is no more than about 1%, 5% or 10%.
  • biodegradable polymers that can be used to form biodegradable endoprostheses (e.g., stents) include without limitation polylactide, poly(trimethylene carbonate), poly(lactide-co-glycolide), poly(lactide-co-E-caprolactone), poly(lactide-co- trimethylene carbonate), polyhydroxybutyrates, polyhydroxyvalerates, polyorthoesters, polyanhydrides, polyiminocarbonates, and copolymers, blends and combinations thereof, wherein lactide includes L-lactide, D-lactide and D,L-lactide.
  • the polymeric material or the body of a biodegradable endoprosthesis is comprises a polylactide homopolymer or copolymer, wherein lactide includes L-lactide, D-lactide and D,L-lactide.
  • the body of the biodegradable endoprosthesis comprises a poly(L- lactide) homopolymer or copolymer.
  • a biodegradable endoprosthesis comprises poly(L-lactide-co- glycolide) copolymer or polymer comprising about 80% to about 90% L-lactide and about 10% to about 20% glycolide by weight or molarity.
  • the poly(L-lactide- co-glycolide) copolymer or polymer comprises about 85% L-lactide and about 15% glycolide by weight or molarity.
  • a biodegradable endoprosthesis is formed from a poly(L-lactide-co-E-caprolactone) copolymer or polymer comprising about 85% to about 95% L-lactide and about 5% to about 15% ⁇ -caprolactone by weight or molarity.
  • the poly(L-lactide-co-E-caprolactone) copolymer or polymer comprises about 90% L-lactide and about 10% ⁇ -caprolactone by weight or molarity.
  • biodegradable polymers that can be used to form
  • biodegradable endoprostheses include without limitation polyesters,
  • polyanhydrides polyalkylene carbonates, polyiminocarbonates, polyorthoesters, poly(ether esters), polyamides, poly(ester amides), polyamines, poly(ester amines), polyurethanes, poly(ester urethanes), polyureas, poly(ethylene imines), polyphosphazenes, polyphosphates, polyphosphonates, polysulfonates, polysulfonamides, polyethers, polyacrylic acids, polycyanoacrylates, polyvinylacetate, polylactide, polyglycolide, poly(malic acid), poly(L- lactic acid-co-D,L-lactic acid), poly(lactide-co-glycolide), poly(E-caprolactone),
  • polydioxanone poly(trimethylene carbonate), poly(ethylene carbonate), poly(propylene carbonate), poly(ethylene carbonate-co-trimethylene carbonate), poly(lactic acid-co- trimethylene carbonate), poly(L-lactic acid-co-trimethylene carbonate-co-D,L-lactic acid), poly(glycolic acid-co-trimethylene carbonate), poly(£-caprolactone-co-trimethylene carbonate), poly(glycolic acid-co-trimethylene carbonate-co-dioxanone),
  • polyhydroxybutyrates polyhydroxyvalerates, poly(3-hydroxybutyrate-co-hydroxyvalerate), poly(ethyl glutamate), modified poly(ethylene terephthalate), poly(butylene succinate), poly(butylene succinate adipate), poly(butylene succinate terephthalate), poly(butylene adipate-co-terephthalate), starch-based polymers, hyaluronic acid, regenerated cellulose, oxidized and non-oxidized regenerated cellulose copolymers, and copolymers, blends and combinations thereof, wherein lactic acid/lactide includes L-lactic acid/L-lactide, D-lactic acid/D-lactide and D,L-lactic acid/D,L-lactide.
  • the biodegradable polymers can be homopolymers, block copolymers, random copolymers, graft copolymers, polymers having functional groups (e.g., acidic, basic, hydrophilic, amino, hydroxyl, thiol, and/or carboxyl groups) along the backbone and/or at the ends, or a blend of two or more homopolymers and/or copolymers.
  • the body of a biodegradable endoprosthesis is comprised of a random copolymer.
  • the body of a biodegradable endoprosthesis is comprised of a biodegradable blend or mixture of polymers.
  • the biodegradable polymer comprises one or more polymers.
  • the polymeric material/article and/or the tubular body and/or the prosthesis or device can undergo any of a variety of modification or treatments (e.g., longitudinal extension, radial expansion, heating, cooling, quenching, pressurizing, vacuuming, exposure/incorporation of solvents, incorporation of additive, removal of additives or impurities, or exposure to radiation or carbon dioxide, or a combination thereof) designed to control or enhance characteristics (e.g., crystallinity, strength, toughness and degradation, Tg, recoil, shortening, expansion) of the article, the tubular body, and/or the prosthesis or device.
  • modification or treatments e.g., longitudinal extension, radial expansion, heating, cooling, quenching, pressurizing, vacuuming, exposure/incorporation of solvents, incorporation of additive, removal of additives or impurities, or exposure to radiation or carbon dioxide, or a combination thereof
  • characteristics e.g., crystallinity, strength, toughness and degradation, Tg, recoil, short
  • biodegradable implantable device comprising a polymeric polymer (including homopolymer or copolymer) described herein.
  • the modification comprises annealing/heating the
  • biodegradable polymer e.g., tubular body
  • the biodegradable polymer or copolymer or tubular body or stent is heated to a temperature at about Tg, or below Tg from about 1°C to about 50°C below Tg, or from about 5°C to about 25°C below Tg, or from about 10°C to about 15°C below Tg, or above the glass transition temperature (T g ) of the polymeric material and below the melting point (T m ) of the polymeric material for a period of time (e.g., about one minute to about three hours, at one temperature, or more than one temperature in controlled increments), or to a temperature to melt the material, or to a temperature that is of about 1°C-70°C above Tg, or about 5°C-50°C above Tg, or about 10°C -40°C above Tg, or about 15-30°C above Tg; and then is slowly or quickly cooled or quenched to a lower temperature, e.g., to ambient
  • the biodegradable polymer (tube) can be patterned into an endoprosthesis structure (e.g., a structure capable of radial contraction and expansion, such as a stent) by laser cutting or other method known in the art.
  • an endoprosthesis structure e.g., a structure capable of radial contraction and expansion, such as a stent
  • Exemplary stent patterns are described in U.S. Patent Application No. 12/016,077, whose entire disclosure is incorporated herein by reference.
  • the tubular body can be annealed both before and after being patterned into an endoprosthesis structure, or additional annealing steps can be performed so that the biodegradable polymer tube can be subjected to two, three, four or more annealing steps during the fabrication process.
  • the annealing temperature is about 50°C below Tg to about Tg, or 35°C below Tg to about Tg, or about 20°C below Tg to about Tg, or about 10°C below Tg to about Tg, Or about 20°C to about 45°C.
  • an annealing of the tubular body or the stent is performed post radiation or sterilization at a temperature ranging from about 20°C to about 80°C, or from about 25°C to about 50°C, or from about 25°C to about 35°C; for about lminute to about 7 days, or for about 10 minutes to about 3 days, or for about 1 hour to about 1 day.
  • a polymeric material can be made into an article (e.g., a tube) by spraying, dipping, extrusion, molding, injection molding, compression molding, 3-D printing or other process.
  • the polymeric article or tube can be placed under vacuum (e.g., about -25 in. Hg or lower) and/or heated to remove any residual solvents and monomers, and then can be annealed and quenched to increase crystallinity (e.g., degree of crystallinity) of the polymeric material and/or reduce residual or internal stress in the polymeric article or tube.
  • vacuum e.g., about -25 in. Hg or lower
  • crystallinity e.g., degree of crystallinity
  • the polymeric article or tube is placed under vacuum (e.g., at about 1 torr or below) and/or is heated at temperature ranging from below Tg, about Tg, or above Tg, or at elevated temperature (e.g., at about 40 °C or above) to remove any residual water, solvents and monomers, and is then annealed by being heated to a temperature below Tg, about Tg, or above the glass transition temperature (T g ) and below the melting temperature (T m ) of the polymeric material.
  • vacuum e.g., at about 1 torr or below
  • elevated temperature e.g., at about 40 °C or above
  • the annealing temperature is at least about 1 °C, 5 °C, 10 °C, 20 °C, 30 °C, 40 °C or 50 °C higher than the T g , and is at least about 1 °C, 5 °C, 10 °C, 20 °C, 30 °C, 40 °C, 50 °C, 75 °C or 100 °C lower than the T m of the polymeric material.
  • the annealing temperature is at least about 10 °C above the T g and is at least about 20 °C below the T m of the polymeric material.
  • the annealing time is about 1 minute to about 10 days, or about 5 or 30 minutes to about 1 day, or about 15 or 30 minutes to about 12 hours, or about 15 or 30 minutes to about 6 hours, or about 15 or 30 minutes to about 3 hours, or about 1 hour to about 6 hours, or about 1 hour to about 3 hours, or about 1.5 hours to about 2.5 hours. In an embodiment, the annealing time is about 30 minutes to about 6 hours.
  • the polymeric article undergoes one or more cycles of annealing involving heating and cooling, which can, e.g., increase the strength of the material (e.g., polymeric material), reduce residual or internal stress in the polymeric article, and/or control its crystallinity, including its degree of crystallinity and the size, number and distribution of crystals or crystalline regions in the material (e.g., polymeric material).
  • heating and cooling can, e.g., increase the strength of the material (e.g., polymeric material), reduce residual or internal stress in the polymeric article, and/or control its crystallinity, including its degree of crystallinity and the size, number and distribution of crystals or crystalline regions in the material (e.g., polymeric material).
  • the polymeric article is heated at a temperature equal to or greater than the glass transition temperature (T g ) of the first biodegradable polymer or the material (e.g., polymeric material) comprising the polymeric article for a period of time (e.g., at least about 0.1, 0.25, 0.5, 1, 4, 8, 12 or 24 hours), and then quickly or slowly cooled to a lower temperature (e.g., at least about 10 °C, 20 °C, 30 °C, 40 °C or 50 °C below the T g , or to ambient temperature or below) over a period of time (e.g., about 10 sec, 30 sec, 1 min, 10 min, 30 min, 1 hr, 4 hr, 8 hr or 12 hr).
  • the polymeric article is heated at a temperature above the T g and below the melting temperature (T m ) of the first
  • a period of time e.g., at least about 10 sec, 30 sec, 1 min, 10 min, 30 min, 1 hr, 4 hr, 8 hr or 12 hr.
  • the polymeric article is heated at a temperature within the cold crystallization temperature range of the first biodegradable polymer or the material (e.g., polymeric material) comprising the polymeric article for a period of time (e.g., at least about 0.1, 0.25, 0.5, 1, 4, 8, 12 or 24 hours), and then cooled to a lower temperature (e.g., at least about 10 °C, 20 °C, 30 °C, 40 °C or 50 °C below the T g , or to ambient temperature or below) over a period of time (e.g., about 10 sec, 30 sec, 1 min, 10 min, 30 min, 1 hr, 4 hr, 8 hr or 12 hr).
  • a period of time e.g., at least about 10 sec, 30 sec, 1 min, 10 min, 30 min, 1 hr, 4 hr, 8 hr or 12 hr.
  • the polymeric article is heated at a temperature equal to or greater than the T m of the first biodegradable polymer or the material (e.g., polymeric material) comprising the polymeric article for a period of time (e.g., at least about 0.1, 0.25, 0.5, 1, 4, 8, 12 or 24 hours) to melt crystalline regions of the first biodegradable polymer or the material (e.g., polymeric material), and then cooled to a lower temperature (e.g., at least about 10 °C, 20 °C, 30 °C, 40 °C or 50 °C below the T g , or to ambient temperature or below) over a period of time (e.g., about 10 sec, 30 sec, 1 min, 10 min, 30 min, 1 hr, 4 hr, 8 hr or 12 hr).
  • a period of time e.g., at least about 10 sec, 30 sec, 1 min, 10 min, 30 min, 1 hr, 4 hr, 8 h
  • the polymeric material is treated wherein the treatment comprises inducing or incorporation of monomers or polymers including co-polymers wherein the one or more monomers or polymers amounts in the polymeric material or the stent after treatment ranges from 0.001% to 10% by weight, preferably ranges from 0.1% to 5% by weight, more preferably ranges from 0.1% to 3% by weight.
  • the polymeric material is treated wherein the treatment comprises inducing or incorporation of monomers or polymers wherein the one or more monomers or polymers amounts in the polymeric material or the stent after treatment ranges from 0.001% to 10% by weight, preferably ranges from 0.1% to 5% by weight, more preferably ranges from 0.1% to 3% by weight and wherein the stent at body temperature is capable to expand from a crimped configuration to a deployed diameter without fracture and have sufficient strength to support a body lumen.
  • the polymeric material is treated wherein the treatment comprises inducing or incorporation of monomers or polymers wherein the one or more monomers or polymers amounts in the polymeric material or the stent after treatment ranges from 0.001% to 10% by weight, preferably ranges from 0.1% to 5% by weight, more preferably ranges from 0.1% to 3% by weight and wherein the one or more monomers or polymers substantially does not affect degradation of the stent (preferably does not affect degradation the stent.
  • the polymeric material is treated wherein the treatment comprises inducing or incorporation of monomer or polymer wherein the one or more monomer or polymer amounts in the polymeric material or the stent after treatment ranges from 0.001% to 10% by weight, preferably ranges from 0.1% to 5% by weight, more preferably ranges from 0.1% to 3% by weight and wherein the one or more monomer or polymer preferably substantially does not affect the stent degradation (preferably accelerates the stent degradation) and wherein the one or more monomer or polymer substantially remains in the stent in the ranges described above before deployment of the stent )wherein the stent at body temperature is capable to expand from a crimped
  • the one or more monomer or polymer amounts are greater than 0.1%, preferably greater than 1%, more preferably greater than 3%, more preferably greater than 5% by weight of the polymeric material.
  • monomers or polymers include lactides, glycolides, caprolactones, lactides and glycolides, lactides and caprolactones to name a few. Incorporation of monomers can take place, for example by spraying as described herein, or inducing by radiation.
  • Preferred Tg ranges from 20°C to 50°C, more preferred from greater than 37°C to less than 50°C.
  • Preferred crystallinity ranges from 1% to 60%, preferably from 1% to 55%, more preferably from 1% to 45%, most preferably from 1% to 35%.
  • the polymeric material preferably has an initial diameter, preferably 1-1.5 times the deployment diameter of the stent.
  • the stent is capable of being crimped from an expanded diameter to a crimped diameter, and at body temperature is capable to expand from a crimped configuration to a deployed diameter without fracture and have sufficient strength to support a body lumen.
  • Examples of polymeric material are materials comprising lactide, lactide and glycolide, or lactides and caprolactones, or a combination thereof.
  • the diameter of the tubular body or the polymeric material or the stent may, at the time of treatment (e.g., treatment diameter), be optionally smaller or optionally greater than the deployment diameter, where the deployment diameter may include, for example, the diameter of the tubular body or the stent within a lumen.
  • the treatment diameter may be 1-2 times the deployment diameter, or 1-1.9 times the deployment diameter, or 1-1.8 times the deployment diameter, or 1-1.7 times the deployment diameter, or 1-1.6 times the deployment diameter, or 1-1.5 times the deployment diameter, or 1-1.4 times the deployment diameter, or 1-1.3 times the deployment diameter, or 1-1.2 times the deployment diameter, or 1-1.05 times the deployment diameter.
  • the treatment diameter may be 0.95-1 times the deployment diameter.
  • the treatment diameter may be 0.9-1 times the deployment diameter, or 0.8-1 times the deployment diameter, or 0.7-1 times the deployment diameter, or 0.6-1 times the deployment diameter, or 0.5-1 times the deployment diameter, or 0.4-1 times the deployment diameter, or 0.3-1 times the deployment diameter, or 0.2-1 times the deployment diameter.
  • the stent expanded/deployed diameter typically is 2mm and higher, 2.5mm and higher, 3mm and higher, 3.5mm and higher, 4mm and higher, 4.5mm and higher, 5mm and higher, 5.5mm and higher.
  • the stent deployed diameter ranges from 2mm-25mm, preferably ranges from 2.5mm to 15mm, more preferably from 3mm to 10mm.
  • the stent length ranges from 1mm to 200cm, preferably from 5mm to 60cm, more preferably from 5mm to 6cm.
  • an annealed polymeric article or tube is quenched by being cooled fast from the annealing temperature to a lower temperature (e.g., at least about 10 °C, 20 °C, 30 °C, 40 °C or 50 °C below the T g , or to ambient temperature or below) over a period of about 1 second to about 1 hour, or about 10 seconds to about 1 hour, or about 30 seconds to about 30 minutes, or about 1 minute to about 30 minutes, or about 1 minute to about 15 minutes, or about 1 minute to about 5 minutes, or about 5 minutes to about 15 minutes, or about 10 seconds to about 1 minute.
  • a lower temperature e.g., at least about 10 °C, 20 °C, 30 °C, 40 °C or 50 °C below the T g , or to ambient temperature or below
  • an annealed article or tube is quenched by being cooled slowly from the annealing temperature to a lower temperature (e.g., at least about 10 °C, 20 °C, 30 °C, 40 °C or 50 °C below the T g , or to ambient temperature or below) over a period of about 1 hour to about 24 hours, or about 1 hour to about 12 hours, or about 1 hour to about 6 hours, or about 2 hours to about 12 hours, or about 4 hours to 12 hours, or about 4 hours to about 8 hours, or about 6 hours to 10 about hours.
  • a lower temperature e.g., at least about 10 °C, 20 °C, 30 °C, 40 °C or 50 °C below the T g , or to ambient temperature or below
  • a heat-treated article or tube is cooled to a temperature below ambient temperature for a period of about 1 minute to about 96 hours, or about 24 hours to about 72 hours, or about 30 minutes to about 48 hours, or about 1 hour to about 48 hours, or about 1 hour to about 36 hours, or about 1 hour to about 24 hours, or about 1 hour to about 12 hours, or about 4 hours to about 12 hours, to stabilize the crystals and/or terminate crystallization in the polymeric material.
  • Annealing and quenching of the polymeric article or tube can initiate and promote nucleation of crystals in the polymeric material, increase the mechanical strength of the material (e.g., polymeric material) comprising the polymeric article or tube, and/or reduce residual/internal stress in the polymeric article or tube.
  • the annealing temperature and duration and the cooling temperature and rate of cooling can be controlled to optimize the size, number and distribution of the crystals and crystalline regions in the material (e.g., polymeric material) and the strength thereof.
  • an unannealed or annealed polymeric article or tube is exposed to ionizing radiation (e.g., e-beam or gamma radiation) at, above or below ambient temperature, with a single dose or multiple doses of radiation totaling about 1 kGray (kGy) to about 100 kGy, or about 10 kGy to about 50 kGy, or about 10 kGy to about 30 kGy, or about 20 kGy to about 60 kGy, or about 20 kGy to about 40 kGy.
  • ionizing radiation e.g., e-beam or gamma radiation
  • an unannealed or annealed article or tube is cooled to reduced temperature (e.g., below 0 °C) and then is exposed to a single dose or multiple doses of ionizing radiation (e.g., e-beam or gamma radiation) totaling about 10 kGy to about 50 kGy.
  • reduced temperature e.g., below 0 °C
  • ionizing radiation e.g., e-beam or gamma radiation
  • Examples include treating the tubular body by heating the tubular body after forming to temperature at about Tg or lower than Tg or within 10°C higher than Tg, of the biodegradable polymeric material Tg, for duration ranging from a fraction of a second to 7 days, or 5 seconds to 7 days, preferably from 15 seconds to 1 day, more preferably from 30 seconds to 5 hours, and optionally cooling or quenching after heating to above ambient, ambient temperatures or below ambient.
  • the heating can take place once or more than once at various stages of the tubular body or stent prosthesis fabrication.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, or spraying and has been treated by heating the tubular body at about Tg or lower of the biodegradable polymeric material Tg, said biodegradable polymeric material is substantially amorphous after said treatment and has a Tg greater than 37°C, and the stent prosthesis at body temperature is radially expandable and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, or spraying and has been treated by heating the tubular body at about Tg or lower of the biodegradable polymeric material Tg, said biodegradable polymeric material has crystallinity of 10%-60% (or 10%-50% or 10%-40% or 10% to 30% or 10%-20% or 0%-10% or 0% to 30%) after said treatment and has a Tg greater than 37°C, and the stent prosthesis at body temperature is radially expandable and has sufficient strength to support a body lumen.
  • the Tg is greater than 37°C and less than 60°C, preferably greater than 37°C and less than 55°C, more preferably greater than 37°C and less than 45°C, more preferably greater than 35°C and less than 45°C.
  • tubular body or the stent or the biodegradable material sees after forming.
  • examples include treating the tubular body by heating the tubular body after forming to temperature at about Tg or lower than Tg or within 10°C higher than Tg, or having one (or more than one) heat treatment above Tg, of the biodegradable polymeric material Tg, for duration ranging from a fraction of a second to 7days, preferably from 15 seconds to 1 day, more preferably from 30 seconds to 5 hours, and optionally cooling or quenching, after heating, to above ambient, ambient temperatures or below ambient.
  • the heating can take place once or more than once at various stages of the tubular body or stent prosthesis fabrication.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, or spraying and has been treated by heating the tubular body at about Tg or lower of the biodegradable polymeric material Tg and one heat treatment above Tg, said biodegradable polymeric material is substantially amorphous after said treatments and has a Tg greater than 37°C, and the stent prosthesis at body temperature is radially expandable and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, or spraying and has been treated by heating the tubular body at about Tg or lower of the biodegradable polymeric material Tg and one heat treatment above Tg, said biodegradable polymeric material has crystallinity of 10%-60% (or 10%-50% or 10%-40% or 10% to 30% or 10%-20% or 0%-10% or 0% to 30%) after said treatment and has a Tg greater than 37°C, and the stent prosthesis at body temperature is radially expandable and has sufficient strength to support a body lumen.
  • the Tg is greater than 37°C and less than 60°C, preferably greater than 37°C and less than 55°C, more preferably greater than 37°C and less than 45°C, more preferably greater than 35°C and less than 45°C.
  • Examples include treating the tubular body by heating the tubular body after forming to temperature at about Tg or lower than Tg or within 10°C higher than Tg, of the biodegradable polymeric material Tg, for duration ranging from a fraction of a second to 7 days, or 5 seconds to 7days, preferably from 15 seconds to 1 day, more preferably from 30 seconds to 5 hours, and optionally cooling or quenching after heating to above ambient, ambient temperatures or below ambient.
  • the heating can take place once or more than once at various stages of the tubular body or stent prosthesis fabrication.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, or spraying and has been treated by heating the tubular body at about Tg or lower of the biodegradable polymeric material Tg, said biodegradable polymeric material is substantially amorphous after said treatment and has a Tg greater than 37°C, and the stent prosthesis at body temperature is radially expandable and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, or spraying and has been treated by heating the tubular body at about Tg or lower of the biodegradable polymeric material Tg, said biodegradable polymeric material has crystallinity of 10%-60% (or 10%-50% or 10%-40% or 10% to 30% or 10%-20% or 0%-10% or 0% to 30%) after said treatment and has a Tg greater than 37°C, and the stent prosthesis at body temperature is radially expandable and has sufficient strength to support a body lumen.
  • the Tg is greater than 37°C and less than 60°C, preferably greater than 37°C and less than 55°C, more preferably greater than 37°C and less than 45°C, more preferably greater than 35°C and less than 45°C.
  • the endoprosthesis e.g., a stent
  • the polymeric article e.g., a polymeric tube
  • the endoprosthesis or the polymeric article is pressurized to at least about 100 psi, 200 psi, 300 psi, 400 psi, 500 psi, 600 psi or 700 psi, with or without added heat, and in the presence or absence of carbon dioxide gas or liquid.
  • the material (e.g., polymeric material) comprising the body of an endoprosthesis e.g., a stent
  • has increased strength and/or crystallinity e.g., through induced or increased orientation of crystals, crystalline regions or polymer chains
  • has reduced residual or internal stress by at least heating the endoprosthesis and/or the polymeric article (e.g., a polymeric tube) from which it is formed at a temperature equal to the T g , or above the T g and below the T m , or equal to or above the T m , of the material (e.g., polymeric material), or below Tg, for a period of time (e.g., at least about 0.01, 1, 4, 8, 12, 24, 36 or 48 hours), and quickly or slowly cooling the endoprosthesis and/or the polymeric article to a lower temperature (e.g., at least about 10 °C, 20 °C, 25°C, 30 °C, 40 °
  • the material e.g., polymeric material
  • an endoprosthesis e.g., a stent
  • the material has increased strength and/or crystallinity, and/or has reduced residual or internal stress, by heating the
  • endoprosthesis and/or the polymeric article e.g., a polymeric tube
  • a temperature at least about 1 °C, 5 °C, 10 °C, 20 °C, 30 °C, 40 °C to about 50 °C (e.g., polymeric material) for a period of time (e.g., at least about 0.1, 4, 8, 12, 24, 36 or 48 hours), and quickly or slowly cooling the endoprosthesis and/or the polymeric article to lower temperature (e.g., at least about 10 °C, 20 °C, 25°C, 30 °C, 40 °C or 50 °C below the T g , or to ambient temperature or below).
  • a period of time e.g., at least about 0.1, 4, 8, 12, 24, 36 or 48 hours
  • the endoprosthesis and/or the polymeric article are heated at a temperature equal to or no more than about 1 °C, 5 °C, 10 °C, 15 °C, 20 °C, 25 °C or 30 °C below the temperature used to induce or increase orientation of crystals, crystalline regions or polymer chains of the material (e.g., polymeric material) comprising the endoprosthesis or the polymeric article.
  • a temperature equal to or no more than about 1 °C, 5 °C, 10 °C, 15 °C, 20 °C, 25 °C or 30 °C below the temperature used to induce or increase orientation of crystals, crystalline regions or polymer chains of the material (e.g., polymeric material) comprising the endoprosthesis or the polymeric article.
  • a polymeric material comprising the body of the endoprosthesis and/or a polymeric material comprising any coating on the endoprosthesis can be crosslinked by exposure to radiation (e.g., UV radiation or ionizing radiation, such as e-beam or gamma radiation), exposure to heat, use of a crosslinker, or use of a crosslinking agent and an initiator, as described herein.
  • radiation e.g., UV radiation or ionizing radiation, such as e-beam or gamma radiation
  • the polymeric material(s) are crosslinked by exposure to e-beam or gamma radiation having a cumulative dose of about 1 kGy to about 1000 KGy, or about 5 kGy to about 100 kGy, or about 10 kGy to about 50 kGy, or about 10 kGy to about 30 kGy, or about 20 kGy to about 60 kGy, or about 20 kGy to about 40 kGy.
  • Crosslinking of the polymeric material(s) can be performed, e.g., to increase their crystallinity and/or reduce recoil of an endoprosthesis (e.g., a stent) comprised of the polymeric material(s).
  • the biodegradable stent material has increased crystallinity by increasing orientation of polymer chains with in the biodegradable stent material in radial and/or longitudinal direction by drawing, pressurizing and/or heating the stent material.
  • drawing, pressurizing and/or heating the stent material occurs simultaneously or sequentially.
  • the biodegradable stent material is placed with at least one surface against a non deformable surface and is pressurized to at least 200 psi, preferably to at least 300 psi, more preferably to at least 500 psi. In another embodiment, the biodegradable stent material is pressurized to at least 200 psi, preferably to at least 300 psi, more preferably to at least 500 psi.
  • the biodegradable stent material tube is placed with in a larger diameter non deformable tube and is pressurized to at least 200 psi, preferably to at least 300 psi, more preferably to at least 500 psi. In another embodiment, the biodegradable stent material tube is pressurized to at least 200 psi, preferably to at least 300 psi, more preferably to at least 500 psi.
  • the biodegradable stent material has increased crystallinity by increasing the orientation of the polymer chains by at least heating the biodegradable stent material above its glass transition temperature (Tg) and below its melting temperature.
  • Tg glass transition temperature
  • the biodegradable stent material has increased crystallinity by heating the material to a temperature at least 10°C higher than its Tg, preferably at least 20°C higher, more preferably at least 30°C higher than the Tg of the biodegradable stent material.
  • biodegradable stent material has increased crystallinity after drawing, heat and/or pressurizing and annealing at elevated temperature with or without vacuum.
  • the annealing temperature is below the temperature used for orientation of the polymer chains of the biodegradable stent material. In another embodiment, the annealing temperature is at most 20°C below, preferably at most 15°C below, more preferably at most 10°C below the temperature for orientation of the polymer chains of the biodegradable stent material.
  • the biodegradable stent material after annealing is quenched below Tg of the biodegradable stent material, preferably at least 25°C below Tg, more preferably at least 50°C below Tg of the biodegradable stent material.
  • the polymeric material or the tubular body formed there from can be modified to control crystallinity (e.g., degree of crystallinity) of the polymeric material.
  • the substantially amorphous or semi-crystalline polymeric material or the tubular body formed therefrom undergoes a modification treatment to introduce a desired degree of crystallinity into the polymeric material to increase the strength of the polymeric material without substantially lengthening its degradation time.
  • tubular body comprising the polymer or copolymer comprised of at least one of PLLA, PLLA-PCL, or PLGA, wherein the tubular body or stent is substantially amorphous or semi crystalline after modification.
  • the tubular body comprising the polymer or copolymer is comprised of at least one of PLLA, PLLA-PCL, or PLGA, wherein the tubular body or stent is substantially amorphous or semi crystalline after modification, and wherein the crystallinity ranges from about 5% to about 40%.
  • the tubular body comprising the polymer or copolymer is comprised of at least one of PLLA, PLLA-PCL, PLGA, wherein the tubular body or stent is substantially amorphous or semi crystalline after modification, and wherein the crystallinity ranges from about 5% to about 30%.
  • the tubular body comprising the polymer or copolymer is comprised of at least one of PLLA, PLLA-PCL, PLGA, wherein the tubular body or stent is substantially amorphous or semi crystalline after modification and wherein the crystallinity ranges from about 5% to about 25%.
  • the treated stent or other endoprosthesis can be crimped onto a delivery balloon using mechanical crimpers comprising of wedges such as crimpers from Machine Solutions, Fortimedix, or others.
  • the stent can also be crimped by placing the stent in a shrink tube and stretching the shrink tube slowly at a rate of 0.1 to 2 inches/minutes, more preferably 0.2 to 0.5 inches/minutes until the stent is crimped to the desired crimped diameter.
  • the stent is heated to a temperature of 20°C below the Tg to 10°C above the Tg for 30 minutes, more preferably to 10°C below the Tg to Tg, and most preferably at the Tg of the stent material.
  • the ability for the stent to remain the crimped diameter can further be improved by fixing the stent in the crimped diameter while exposing it to a temperature of 20°C below the Tg to 10°C above the Tg for 30 minutes, more preferably to 10°C below the Tg to Tg, and most preferably at the Tg of the stent material, for 1 minute to 24 hours, more preferably 15 minutes to 1 hour. After holding at this crimping temperature, it is preferred to fix the stent in the crimped diameter while at or below ambient temperatures until further processing (i.e., sterilization).
  • the stent can either be crimped while it is on the balloon of the stent delivery catheter or first crimped alone and then slipped onto the balloon of the catheter.
  • the crimped stent is cooled below ambient temperature to lock in the crystals or terminate crystallization for 1 minute to 96 hours, more preferably 24 hours to 72 hours.
  • the final crimped stent on the catheter is sterilized by 25 to 30 kGy dose of ebeam, typically with a single dose of 30 kGy or with multiple smaller doses (e.g., 3 x 10 kGy).
  • the stent system is usually kept below ambient temperature before, during and/or after multiple smaller doses of sterilization.
  • the stent that has been packaged and sterilized can also be exposed to heat treatment like that described above.
  • the biodegradable polymer stent is heated at about the Tg of the biodegradable stent material during expansion of the stent. The temperature during expansion can range from 10°C above Tg to 10°C below Tg.
  • the processes provide means to minimize stent recoil to less than 10% after expansion from the crimped state to an expanded state.
  • a stent can be crimped to a smaller diameter using a mechanical crimper.
  • a stent can also be crimped by placing the stent in a shrink tube and stretching the shrink tube slowly at a rate of about 0.1 to about 2 inches/minute, or about 0.1 to about 1 inch/minute, or about 0.2 to about 0.5 inch/minute, until the stent is crimped to the desired diameter.
  • a stent can be crimped onto the balloon of a delivery catheter, or can be crimped and then mounted onto the balloon of a catheter to provide a stent delivery system.
  • a stent is crimped at ambient temperature, or is crimped at a temperature (crimping temperature) of at least about 30 °C, 35 °C, 40 °C, 45 °C or 50 °C, and then the stent crimped at elevated temperature is cooled to a lower temperature (e.g., at least about 5 °C, 10 °C, 15 °C, 20 °C, 25 °C or 30 °C below the crimping temperature, or to ambient temperature or below).
  • the stent is crimped at about 35 °C or above, and then the crimped stent is cooled to a temperature at least about 5 °C below the crimping temperature.
  • the crimping temperature is at or below the T g of the material (e.g., polymeric material) of which the stent body is composed, or at least about 1 °C, 5 °C, 10 °C, 15 °C, 20 °C, 25 °C, 30 °C, 35 °C, 40 °C, 45 °C or 50 °C below the T g .
  • the crimping temperature is at least about 5 °C below the T g of the material (e.g., polymeric material) comprising the stent body.
  • a stent is exposed to the crimping temperature for at least about 0.5, 1, 3, 5 or 10 minutes and allowed to reach the crimping temperature prior to being crimped.
  • the stent can be exposed to the crimping temperature using a heated crimper.
  • the crimped stent can be stabilized in the crimped state as described herein.
  • the crimped stent is cooled below ambient temperature for a period of about 1 minute to about 96 hours, or about 24 hours to about 72 hours, or about 30 minutes to about 48 hours, or about 1 hour to about 48 hours, or about 1 hour to about 36 hours, or about 1 hour to about 24 hours, or about 1 hour to about 12 hours, or about 4 hours to about 12 hours, to stabilize the stent, and/or stabilize the crystals and/or terminate crystallization in the stent polymeric material.
  • a stent is exposed to carbon dioxide gas at elevated pressure (e.g., at least about 100, 150, 200, 250, 300, 350, 400, 450 or 500 psi) for a period of time (e.g., at least about 10, 20 or 30 minutes, or at least about 1, 2 or 3 hours), e.g., to soften the material (e.g., polymeric material) comprising the body of the stent and/or a coating on the stent.
  • elevated pressure e.g., at least about 100, 150, 200, 250, 300, 350, 400, 450 or 500 psi
  • a period of time e.g., at least about 10, 20 or 30 minutes, or at least about 1, 2 or 3 hours
  • the stent can be crimped at or below the T g of the material (e.g., polymeric material) comprising the body of the stent (e.g., at least about 1 °C, 5 °C, 10 °C, 15 °C, 20 °C, 25 °C, 30 °C, 35 °C, 40 °C, 45 °C or 50 °C below the T g ), or at about ambient temperature to about 50 °C.
  • the material e.g., polymeric material
  • the body of the stent e.g., at least about 1 °C, 5 °C, 10 °C, 15 °C, 20 °C, 25 °C, 30 °C, 35 °C, 40 °C, 45 °C or 50 °C below the T g
  • the material e.g., polymeric material
  • the body of the stent e.g., at least about 1 °C, 5 °C, 10 °
  • An endoprosthesis e.g., a stent or a stent delivery system
  • the polymeric article e.g., a polymeric tube
  • ionizing radiation such as electron beam or gamma radiation
  • ethylene oxide gas e.g., for purposes of sterilization
  • such exposure can serve as a modification or treatment in that it can, e.g., control crystallinity (e.g., degree of crystallinity) and/or enhance the strength of the material (e.g., polymeric material) comprising the polymeric article or the endoprosthesis.
  • the polymeric article and/or the endoprosthesis are exposed to a single dose or multiple doses of e-beam or gamma radiation totaling about 5 or 10 kGy to about 50 kGy, or about 20 kGy to about 40 kGy of radiation, e.g., a single dose of 30 kGy or multiple smaller doses (e.g., 3 x 10 kGy doses), where the polymeric article and/or the endoprosthesis are cooled to low temperature (e.g., about -10 °C to about -30 °C, or about -20 °C) for a period of time (e.g., at least about 20, 30 or 40 minutes) prior to exposure to the single dose or to each of the multiple doses of radiation.
  • low temperature e.g., about -10 °C to about -30 °C, or about -20 °C
  • a period of time e.g., at least about 20, 30 or 40 minutes
  • the polymeric article and/or the endoprosthesis are exposed to a single dose or multiple doses of e-beam or gamma radiation totaling about 10 kGy to about 50 kGy, or about 30 kGy.
  • a polymeric article and/or an endoprosthesis that have been exposed to ionizing radiation or ethylene oxide gas can also undergo one or more other modification treatments (e.g., heating or annealing) described herein.
  • an endoprosthesis e.g., a stent
  • a polymeric tube that has a (e.g., inner or outer) diameter substantially equal to or smaller than an intended deployed (e.g., inner or outer) diameter of the
  • an endoprosthesis e.g., a stent
  • a polymeric tube that has a (e.g., inner or outer) diameter, either when the tube is formed or after the tube is radially expanded to a second larger diameter, larger than an intended deployed (e.g., inner or outer) diameter of the endoprosthesis.
  • Patterning a stent from a polymeric tube having a (e.g., inner or outer) diameter larger than an intended deployed (e.g., inner or outer) diameter of the stent can impart advantageous characteristics to the stent, such as reducing radially inward recoil of the stent after deployment.
  • a stent is patterned from a polymeric tube having a (e.g., inner or outer) diameter about 0.85, 0.90, 1.0, 1.05 to about 1.5 times, or about 1.1 to about 1.5 times, or about 1.1 to about 1.3 times, or about 1.15 to about 1.25 times, smaller, same, or larger than an intended deployed (e.g., inner or outer) diameter of the stent.
  • the stent is patterned from a polymeric tube having a (e.g., inner or outer) diameter about 1.1 to about 1.3 times larger than an intended deployed (e.g., inner) diameter of the stent.
  • a stent having a deployed (e.g., inner or outer) diameter of about 2.5, 3 or 3.5 mm can be patterned from a tube having a (e.g., inner or outer) diameter of about 2.75, 3.3 or 3.85 mm (1.1 times larger), or about 3.25, 3.9 or 4.55 mm (1.3 times larger), or some other (e.g., inner or outer) diameter larger than the deployed (e.g., inner or outer) diameter of the stent.
  • the initial diameter of the formed tube is larger than the crimped diameter (e.g., crimped diameter on a delivery system) of the stent prosthesis wherein the tubular body is expanded to a second larger diameter than the initial diameter before patterning or before crimping to the crimped diameter; or wherein the tubular body remains substantially the same diameter before patterning or before crimping to a crimped diameter; or wherein the tubular body is crimped to a smaller diameter than the initial formed diameter before patterning or after patterning.
  • the crimped diameter e.g., crimped diameter on a delivery system
  • the initial diameter of the formed tube is smaller than the crimped diameter of the stent prosthesis wherein the tubular body is expanded to a second larger diameter than the initial diameter before patterning or before crimping; or wherein the tubular body remains substantially the same diameter before patterning or before crimping; or wherein the tubular body is crimped to a smaller diameter than the crimped diameter of the stent prosthesis before patterning or after patterning.
  • the initial diameter of the formed tubular body is greater than 0.015 inches, or greater than 0.050 inches, or greater than 0.092 inches, or greater than 0.120 inches, or greater than 0.150 inches.
  • Stent prosthesis intended deployment diameter is the diameter of the labeled delivery system or balloon catheter. For example when a stent prosthesis is crimped onto a balloon labeled 3.0 mm diameter, the stent prosthesis' intended deployment diameter is 3.0mm.
  • self expandable stent crimped onto a delivery system is labeled a certain deployment diameter.
  • the stent cut from a polymeric tube can be any kind of stent and can have any pattern and design suitable for its intended use, including any kind of stent and any pattern and design described herein. Further, the stent can be a fully self-expandable stent, a balloon- expandable stent, or a stent capable of radially self-expanding prior to balloon expansion to an intended deployed diameter.
  • the stent material may lose some crystallinity during stent cutting.
  • the stent annealed after cutting and/or a second time to re-crystallize the polymer to a higher crystallinity.
  • the cut stent may be annealed a second time as generally described above. Annealing/heating followed by cooling as described above can be repeated one or more times to further increase crystallinity.
  • the heat treated stent is cooled below ambient temperature to lock in the crystals or terminate crystallization for 1 minute to 96 hours, more preferably 24 hours to 72 hours.
  • the polymeric article is a polymeric tube and the structure is a substantially cylindrical structure.
  • the substantially cylindrical structure is a mandrel.
  • the polymeric tube is substantially concentric.
  • the polymeric tube has a concentricity of about 0.0025 inch (about 64 microns) or less, or about 0.002 inch (about 51 microns) or less, or about 0.0015 inch (about 38 microns) or less, or about 0.001 inch (about 25 microns) or less, or about 0.0005 inch (about 13 microns) or less, or about 0.00025 inch (about 6 microns) or less.
  • concentricity is two times the distance between the centers of the inner and outer diameters of the tube.
  • the stent is patterned from a polymeric tube that has a (e.g., inner) diameter substantially equal to an intended deployment (e.g., inner) diameter or the maximum allowable expansion (e.g., inner) diameter of the stent.
  • the stent is patterned from a polymeric tube that has a (e.g., inner) diameter greater than (e.g., at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45% or 50% greater than) an intended deployment (e.g., inner) diameter or the maximum allowable expansion (e.g., inner) diameter of the stent.
  • the stent is patterned from a polymeric tube that has a (e.g., inner) diameter at least about 10% greater than an intended deployment (e.g., inner) diameter or the maximum allowable expansion (e.g., inner) diameter of the stent.
  • the stent is patterned from a polymeric tube that has a (e.g., inner) diameter of about 2.5 mm to about 4.5 mm, or about 2.75 mm to about 4.5 mm, or about 3 mm to about 4.5 mm, or about 2.75 mm to about 4 mm, or about 3 mm to about 4 mm, or about 3.3 mm to about 3.8 mm.
  • the stent is patterned from a polymeric tube that has a (e.g., inner) diameter of about 2.75 mm to about 4.5 mm, or about 2.75 mm to about 4 mm.
  • the tubular body or stent prosthesis diameter ranges from about 0.25mm to about 25mm, preferably from about 2mm to about 15mm, more preferably from about 2.5mm to about 10mm, and most preferably from about 3mm to about 7mm.
  • the stent or other endoprosthesis is patterned from a tube of the stent material in an expanded diameter and subsequently crimped to a smaller diameter and fitted onto a balloon of a delivery catheter.
  • the stent is patterned, typically by laser cutting, with the tubing diameter about 1 to 1.3 times, preferably 1.1 to 1.5 times, more preferably 1.15 to 1.25 times, larger the intended deployed diameter. For example, a stent cut at a 3.5mm x 18mm outer diameter is crimped on a 3.0mm x 18mm stent delivery catheter.
  • the unannealed and/or annealed stent is exposed to ebeam or gamma radiation, with single or multiple doses of radiation ranging from 5 kGy to 100 kGy, more preferably from 10 kGy to 50 kGy.
  • An intended deployment diameter is one or more of the following: the labeled deployment diameter of the stent prosthesis.
  • An example is a stent prostheiss IFU or box or label with a certain labeled diameter such as a nominal deployment diameter, for example 3.0mm. It can also be the deployed diameter of the stent prosthesis. It can also be a diameter between a nominal deployment diameter and the rated burst diameter or higher. It can also be the diameter (where in the case of a balloon or mechanical expansion) where the balloon is expanded to at least 90% of the nominal diameter of the balloon. The most preferred embodiment of an intended deployment diameter is the labeled deployment diameter or the nominal deployment diameter.
  • the stent prosthesis when the stent is expanded to at least 1 times or at least 1.1 times or at least 1.15 times or at least 1.2 times or at least 1.25 time or at least 1.3 times, or at least 1.4, or at least 1.5 times deployed diameter or an intended deployment diameter at 37°C, wherein the stent prosthesis is capable of expansion to at least said diameters without breakage/fracture in one or more of the stent prosthesis struts, crowns, or links.
  • the stent when the stent is expanded to at least 1 times or at least 1.1 times or at least 1.15 times or at least 1.2 times or at least 1.25 time or at least 1.3 times a deployed diameter or an intended deployment diameter in a body lumen or in water at 37 °C, wherein the stent prosthesis is capable of expansion to at least said diameters without breakage/fracture in two or more of the stent prosthesis struts, crowns, or links.
  • the stent when the stent is expanded to at least 1 times or at least 1.1 times or at least 1.15 times or at least 1.2 times or at least 1.25 time or at least 1.3 times an intended deployment diameter in a body lumen or in water at 37°C, wherein the stent prosthesis is capable of expansion to at least said diameters without breakage/fracture in three or more of the stent prosthesis struts, crowns, or links.
  • the biodegradable stent prosthesis comprising a biodegradable polymeric material, wherein the polymeric material has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated at a diameter of 1-1.5 times an intended deployment diameter (deployed diameter) of the stent prosthesis, and the stent prosthesis at body temperature is radially expandable and has sufficient strength to support a body lumen and without fracture.
  • the biodegradable stent prosthesis comprising a biodegradable polymeric material, wherein the polymeric material has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated at a diameter of 1-1.5 times an intended deployment diameter (deployed diameter) of the stent prosthesis, wherein the treatment comprises heating the polymeric material to between Tg and Tm (melting temperature of the material), and the stent prosthesis at body temperature is radially expandable and has sufficient strength to support a body lumen and without fracture.
  • the biodegradable stent prosthesis comprising a biodegradable polymeric material, wherein the polymeric material has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated at a diameter of 1-1.5 times an intended deployment diameter of the stent prosthesis, wherein the treatment comprises heating the polymeric material to about Tg or less, and the stent prosthesis at body temperature is radially expandable and has sufficient strength to support a body lumen and without fracture.
  • the biodegradable stent prosthesis comprising a biodegradable polymeric material, wherein the polymeric material has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated at a diameter of 1-1.5 times an intended deployment diameter of the stent prosthesis, wherein the treatment comprises heating the polymeric material to about Tg or less or/and about Tg or more from at least a fraction of a second to about 7 days, and the stent prosthesis at body temperature is radially expandable and has sufficient strength to support a body lumen and without fracture.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated at a diameter of 1-1.5 times an intended deployment diameter of the stent prosthesis, wherein the treatment comprises heating the polymeric material from about Tg or higher, and the stent prosthesis at body temperature is radially expandable and has sufficient strength to support a body lumen.
  • biodegradable stent prosthesis comprising
  • biodegradable polymeric material wherein the polymeric material has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated at a diameter of 1-1.5 times an intended deployment diameter of the stent prosthesis, wherein the treatment comprises heating the polymeric material from about Tg or higher and wherein the polymeric material has crystallinity after treatment between 0% to 60%, and the stent prosthesis at body temperature is radially expandable and has sufficient strength to support a body lumen and without fracture.
  • the biodegradable stent prosthesis comprising a biodegradable polymeric material, wherein the polymeric material has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated at a diameter of 1-1.5 times an intended deployment diameter of the stent prosthesis, wherein the treatment comprises heating the polymeric material from about Tg or higher and wherein the polymeric material has crystallinity after treatment between 0% to 60%, and the stent prosthesis at body temperature is radially expandable and has sufficient strength to support a body lumen and without fracture.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated at a diameter of 0.75-1.5 times an intended deployment diameter of the stent prosthesis, wherein the treatment comprises heating the polymeric material from about Tg or less to about Tg or higher and wherein the polymeric material has crystallinity after treatment between 0% to 60%, and the stent prosthesis at body temperature is radially expandable and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated at a diameter of 0.85-1.5 times an intended deployment diameter of the stent prosthesis, wherein the treatment comprises heating the polymeric material from about Tg or less to about Tg or higher and wherein the polymeric material has crystallinity after treatment between 0% to 60%, and the stent prosthesis at body temperature is radially expandable and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated at a diameter of 0.9-1.5 times an intended deployment diameter of the stent prosthesis, wherein the treatment comprises heating the polymeric material from about Tg or less to about Tg or higher and wherein the polymeric material has crystallinity after treatment between 0% to 60%, and the stent prosthesis at body temperature is radially expandable and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated at a diameter of 0.75-1.5 times an intended deployment diameter of the stent prosthesis, wherein the treatment comprises heating the polymeric material from about Tg or less to about Tg or higher and wherein the polymeric material has crystallinity after treatment between 0% to 60%, and the stent prosthesis is radially expandable to an intended deployment diameter at a temperature ranging from greater than 37°C to 50°C and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated at a diameter of 0.75-1.5 times an intended deployment diameter of the stent prosthesis, wherein the treatment comprises heating the polymeric material from about Tg or less to about Tg or higher and wherein the polymeric material has crystallinity after treatment between 0% to 60%, and the stent prosthesis at body temperature is radially expandable to an intended deployment diameter and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated at a diameter of 0.75-1.5 times an intended deployment diameter of the stent prosthesis, wherein the treatment comprises heating the polymeric material from about Tg or less to about Tg or higher and wherein the polymeric material has crystallinity after treatment between 0% to 60%, and the stent prosthesis at body temperature is radially expandable to at least 1.0 times an intended deployment diameter and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated at a diameter of 0.75-1.5 times an intended deployment diameter of the stent prosthesis, wherein the treatment comprises heating the polymeric material from about Tg or less to about Tg or higher and wherein the polymeric material has crystallinity after treatment between 0% to 60%, and the stent prosthesis at body temperature is radially expandable to at least 1.1 times an intended deployment diameter and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated at a diameter of 0.75-1.5 times an intended deployment diameter of the stent prosthesis, wherein the treatment comprises heating the polymeric material from about Tg or less to about Tg or higher and wherein the polymeric material has crystallinity after treatment between 0% to 60%, and the stent prosthesis at body temperature is radially expandable to at least 1.15 times an intended deployment diameter and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated at a diameter of 0.75-1.5 times an intended deployment diameter of the stent prosthesis, wherein the treatment comprises heating the polymeric material from about Tg or less to about Tg or higher and wherein the polymeric material has crystallinity after treatment between 0% to 60%, and the stent prosthesis at body temperature is radially expandable to at least 1.2 times an intended deployment diameter and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated at a diameter of 0.75-1.5 times an intended deployment diameter of the stent prosthesis, wherein the treatment comprises heating the polymeric material from about Tg or less to about Tg or higher and wherein the polymeric material has crystallinity after treatment between 0% to 60%, and the stent prosthesis is radially expandable to an intended deployment diameter at a temperature ranging from 30°C to less than 37°C and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated and said polymeric material has crystallinity between 0% to 60%, and the stent prosthesis at body temperature is radially expandable to at least 1.0 times an intended deployment diameter of the stent prosthesis and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated and said polymeric material has crystallinity between 0% to 60%, and the stent prosthesis at body temperature is radially expandable to at least 1.1 times an intended deployment diameter of the stent prosthesis and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated and said polymeric material has crystallinity between 0% to 60%, and the stent prosthesis at body temperature is radially expandable to at least 1.11 times an intended deployment diameter of the stent prosthesis and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated and said polymeric material has crystallinity between 0% to 60%, and the stent prosthesis at body temperature is radially expandable to at least 1.12 times an intended deployment diameter of the stent prosthesis and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated and said polymeric material has crystallinity between 0% to 60%, and the stent prosthesis at body temperature is radially expandable to at least 1.13 times an intended deployment diameter of the stent prosthesis and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated and said polymeric material has crystallinity between 0% to 60%, and the stent prosthesis at body temperature is radially expandable to at least 1.14 times an intended deployment diameter of the stent prosthesis and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated and said polymeric material has crystallinity between 0% to 60%, and the stent prosthesis at body temperature is radially expandable to at least 1.15 times an intended deployment diameter of the stent prosthesis and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated and said polymeric material has crystallinity between 0% to 60%, and the stent prosthesis at body temperature is radially expandable to at least 1.16 times an intended deployment diameter of the stent prosthesis and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated and said polymeric material has crystallinity between 0% to 60%, and the stent prosthesis at body temperature is radially expandable to at least 1.17 times an intended deployment diameter of the stent prosthesis and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated and said polymeric material has crystallinity between 0% to 60%, and the stent prosthesis at body temperature is radially expandable to at least 1.18 times an intended deployment diameter of the stent prosthesis and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated and said polymeric material has crystallinity between 0% to 60%, and the stent prosthesis at body temperature is radially expandable to at least 1.18 times an intended deployment diameter of the stent prosthesis and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated and said polymeric material has crystallinity between 0% to 60%, and the stent prosthesis at body temperature is radially expandable to at least 1.19 times an intended deployment diameter of the stent prosthesis and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated and said polymeric material has crystallinity between 0% to 60%, and the stent prosthesis at body temperature is radially expandable to at least 1.2 times an intended deployment diameter of the stent prosthesis and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated and said polymeric material has crystallinity between 0% to 60%, and the stent prosthesis at body temperature is radially expandable to at least 1.21 times an intended deployment diameter of the stent prosthesis and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated and said polymeric material has crystallinity between 0% to 60%, and the stent prosthesis at body temperature is radially expandable to at least 1.22 times an intended deployment diameter of the stent prosthesis and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated and said polymeric material has crystallinity between 0% to 60%, and the stent prosthesis at body temperature is radially expandable to at least 1.23 times an intended deployment diameter of the stent prosthesis and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated and said polymeric material has crystallinity between 0% to 60%, and the stent prosthesis at body temperature is radially expandable to at least 1.24 times an intended deployment diameter of the stent prosthesis and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated and said polymeric material has crystallinity between 0% to 60%, and the stent prosthesis at body temperature is radially expandable to at least 1.25 times an intended deployment diameter of the stent prosthesis and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated and said polymeric material has crystallinity between 0% to 60%, and the stent prosthesis at body temperature is radially expandable to at least 1.26 times an intended deployment diameter of the stent prosthesis and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated and said polymeric material has crystallinity between 0% to 60%, and the stent prosthesis at body temperature is radially expandable to at least 1.27 times an intended deployment diameter of the stent prosthesis and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated and said polymeric material has crystallinity between 0% to 60%, and the stent prosthesis at body temperature is radially expandable to at least 1.28 times an intended deployment diameter of the stent prosthesis and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated and said polymeric material has crystallinity between 0% to 60%, and the stent prosthesis at body temperature is radially expandable to at least 1.29 times an intended deployment diameter of the stent prosthesis and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated and said polymeric material has crystallinity between 0% to 60%, and the stent prosthesis at body temperature is radially expandable to at least 1.3 times an intended deployment diameter of the stent prosthesis and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated and said polymeric material has crystallinity between 0% to 60%, and the stent prosthesis at body temperature is radially expandable to greater than 1.1 times an intended deployment diameter of the stent prosthesis and has sufficient strength to support a body lumen and has recoil of less than 10% from an expanded diameter.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, 3D printing, or spraying, said biodegradable polymeric material has been treated at a diameter of 0.9-1.5 times an intended deployment diameter and said polymeric material after treatment has crystallinity between 0% to 60% and Tg between 37°C and 50°C, and the stent prosthesis at body temperature is radially expandable to greater than 1.1 times an intended deployment diameter of the stent prosthesis and has sufficient strength to support a body lumen and has recoil of less than 10% from an expanded diameter.
  • the tubular body is formed at a diameter of 0.75 to 1.5 times an intended deployment diameter of the stent prosthesis. In yet another embodiment, the tubular body is formed at a diameter less than an intended deployment diameter and expanded to a diameter of 0.75 to 1.5 times an intended deployment diameter before patterning or before crimping the stent prosthesis. In a further embodiment, the tubular body is formed at a diameter less than an intended deployment diameter.
  • biodegradable stent comprising a body comprising or comprised of a material which comprises a biodegradable polymer or copolymer or polymer blend, wherein prior to being balloon-expanded, the stent is capable of radially self-expanding by about 0.025 inch (about 635 microns) or less, or by about 25% or less of an initial crimped diameter of the stent, after being in aqueous condition at about 37 °C in vitro or in vivo for about 5 minutes or less.
  • the stent prior to being balloon-expanded, the stent radially self-expands by about 0.025 inch (about 635 microns) or less, or by about 25% or less of the initial crimped diameter of the stent, after being in aqueous condition at about 37 °C in vitro or in vivo for about 5 minutes or less.
  • biodegradable stent comprising a body which comprises a biodegradable polymer or copolymer, wherein prior to being balloon-expanded, the stent is capable of radially self-expanding by about 0.001-0.025 inches, or about 0.003-0.015 inches, or about 0.005-0.10 inches, or about 0.001 inches or more, or about 0.003 inches or more, or about 0.005 inches or more, or about 0.010 inches or more, or about 0.025 inch or more, or by about 0.25% or more of an initial crimped diameter of the stent, after being in aqueous condition at about 37 °C in vitro or in vivo for about 1 minute or less, or about 5 minutes or less, or about 15 minutes or less.
  • the stent prior to being balloon-expanded, the stent radially self-expands by about 0.025 inch or less, or by about 25% or less of the crimped diameter of the stent, after being in aqueous condition at about 37°C in vitro or in vivo for about 1 minute or less, or about 5 minutes or less, or about 15 minutes or less.
  • the stent is secured in place at least in part from moving at least in one longitudinal direction by about 0.5mm or less, or about 1mm or less, or about 2mm or less, or about 5mm or less, by various means.
  • Such means include at least one of configuring an expandable member proximal and/or distal to the stent, configuring a non expandable member or stops proximal and/or distal to the stent, configuring an attachment or adhesive means adjacent to the stent that does not prevent the stent from being balloon expandable, or configuring a sleeve that ends proximal to the stent, on top of the sent or distal to the stent.
  • the biodegradable stent comprising a body which comprises a biodegradable polymer, or copolymer, polymer blends, polymer blocks, polymer mixture wherein the polymer material is configured to be capable of being balloon expandable and self expanding, wherein prior to being balloon-expanded, the stent self-expands by about 0.001-0.025 inches, or about 0.003-0.015 inches, or about 0.005-0.10 inches, or about 0.001 inches or more, or 0.003 inches or more, or 0.005 inches or more, or 0.010 inches or more, or 0.025 inch or more, or by about 0.25% or more of an initial crimped diameter of the stent, after being in aqueous condition at about 37 °C in vitro or in vivo for about 1 minute, or about 5 minutes or less, or about 15 minutes or less.
  • the biodegradable stent comprising a body which comprises a biodegradable copolymer or polymer, or mixture of 2-3 polymers, or blend of polymers, or wherein the copolymer or polymer is configured to be capable of balloon expandable and self expanding, wherein prior to being balloon-expanded, the stent radially self-expands by about 0.001-0.025 inches, or about 0.003-0.015 inches, or 0.005-0.10 inches, or about 0.001 inches or more, or about 0.003 inches or more, or about 0.005 inches or more, or about 0.010 inches or more, or about 0.025 inch or more, or by about 0.25% or more of an initial crimped diameter of the stent, after being in aqueous condition at about 37 °C in vitro or in vivo for about Iminute or less, or about 5 minutes or less, or about 15 minutes or less, and wherein the stent or the stent body has one or more of the following properties
  • the biodegradable stent comprising a body which comprises a biodegradable copolymer or polymer, wherein the copolymer or polymer is configured to be balloon expandable and self expanding, wherein prior to being balloon-expanded, the stent radially self-expands by about 0.025-0.25inches, or about 0.50-0.15 inches, or about 0.025 inches or more, or about 0.050 inches or more, or about 0.1 inches or more, or by about 0.25% or more of an initial crimped diameter of the stent, after being in aqueous condition at about 37 °C in vitro or in vivo for about 1 minute or less, or about 5 minutes or less, or about 15 minutes or less.
  • the stent is constrained from self expanding using a sheath or other means and then such constraining means is removed, disengaged, or withdrawn, or released after the stent is positioned for deployment, allowing the stent to self deploy.
  • the biodegradable stent comprising a body which comprises a biodegradable copolymer or polymer, wherein the copolymer or polymer is configured to be self expanding, wherein prior to being balloon-expanded, the stent radially self-expanded by about 0.025-0.25 inches, or about 0.50-0.15 inches, or about 0.025 inches or more, or about 0.050 inches or more, or about 0.1 inches or more, or about 0.2 inches or more, or by about 0.25% or more of an initial crimped diameter of the stent, after being in aqueous condition at about 37 °C in vitro or in vivo for about 1 minute or less, or about 5 minutes or less, or about 15 minutes or less.
  • the stent can/may be constrained from self expanding using a sheath or other means until the stent is positioned for deployment and is released from such means for deployment.
  • the stent self expands to a diameter that is less than the final intended deployment diameter of the stent prior to being balloon expanded to the final intended deployment diameter after being in aqueous condition at about 37°C in vitro or in vivo for about 1 minute or less, or about 5 minutes or less, or about 15 minutes or less.
  • the biodegradable stent is a partially or fully self-expandable stent. In other embodiments, the stent is a balloon-expandable stent. In yet other
  • the stent is capable of radially self-expanding initially without a balloon assisting expansion and is then radially expanded to an intended deployment diameter with balloon assistance.
  • the implantable device, prosthesis, and/or articles are configured for uniform expansion (uniformly expanded) during or after either types of expansion from a crimped condition to an expanded condition.
  • the stent prosthesis is substantially uniformly expanded from a crimped condition.
  • the stent prosthesis is uniformly expanded from a crimped state to an expanded state wherein the struts remain intact (or wherein the struts are not broken) after expansion from the crimped state.
  • the stent prosthesis is uniformly expanded at an intended deployment diameter wherein 70% or more of the crowns connecting two struts expand (or open) at an angle (between the struts connected by the crown excluding a link if present) greater than 75 degrees. In other embodiments, the stent prosthesis is uniformly expanded at an intended deployment diameter wherein 70% or more of the crowns connecting two struts expand (or open) at an angle (between the struts connected by the crown excluding a link if present) greater than 90 degrees.
  • the stent prosthesis is uniformly expanded at an intended deployment diameter wherein 70% or more of the crowns connecting two struts expand (or open) at an angle (between the struts connected by the crown excluding a link if present) greater than 100 degrees. In other embodiments, the stent prosthesis is uniformly expanded at an intended deployment diameter wherein 70% or more of the crowns connecting two struts expand (or open) at an angle (between the struts connected by the crown excluding a link if present) greater than 120 degrees.
  • the stent prosthesis is uniformly expanded at an intended deployment diameter wherein 60% or more of the crowns connecting two struts expand (or open) at an angle (between the struts connected by the crown excluding a link if present) greater than 75 degrees or greater than 90 degrees or greater than 120 degrees.
  • a link that joins adjacent rings is connected to crowns. In such cases, these links are not considered struts but are links connecting adjacent rings. Angles for such crowns exclude the presence of links.
  • the biodegradable stent prior to being balloon-expanded (e.g., to an intended deployment diameter), is capable of radially self-expanding, or radially self-expands, by about 0.015 inch (about 381 microns) or less, or by about 0.01 inch (about 254 microns) or less, or by about 0.007 inch (about 178 microns) or less, or by about 0.005 inch (about 127 microns) or less, after being in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37 °C in vitro or in vivo for about 3 minutes or less, or by about 0.025 inch (about 635 microns) or less, or by about 0.02 inch (about 508 microns) or less, or by about 0.015 inch (about 381 microns) or less, or by about 0.01 inch (about 254 microns) or less, after being in aqueous condition
  • the stent prior to being balloon-expanded (e.g., to an intended deployment diameter), is capable of radially self-expanding, or radially self- expands, by about 15% or less, or by about 10% or less, or by about 5% or less, of the initial crimped diameter of the stent after being in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37 °C in vitro or in vivo for about 3 minutes or less, or by about 25% or less, or by about 20% or less, or by about 15% or less, or by about 10% or less, of the initial crimped diameter after being in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37 °C in vitro or in vivo for about 5 minutes or less.
  • aqueous condition e.g., in aqueous solution, water, saline solution or physiological conditions
  • the biodegradable stent prior to being balloon-expanded (e.g., to an intended deployment diameter), is capable of radially self-expanding, or radially self-expands, by about 0.025 inch (about 635 microns) or less, or by about 25% or less of the initial crimped diameter, after being in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37 °C in vitro or in vivo for about 5 minutes or less.
  • aqueous condition e.g., in aqueous solution, water, saline solution or physiological conditions
  • the biodegradable stent prior to being balloon-expanded (e.g., to an intended deployment diameter), is capable of radially self-expanding, or radially self-expands, by more than about 0.025 inch (about 635 microns), or by more than about 25% of the initial crimped diameter, after being in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37 °C in vitro or in vivo for about 15 minutes or less, or about 10 minutes or less, or about 5 minutes or less.
  • aqueous condition e.g., in aqueous solution, water, saline solution or physiological conditions
  • a biodegradable stent comprising a body which comprises a biodegradable polymer, wherein prior to being balloon-expanded, the stent is capable of radially self-expanding by about 0.001-0.025 inches, or about 0.003- 0.015 inches, or about 0.005-0.10 inches, or about 0.001 inches or more, or about 0.003 inches or more, or about 0.005 inches or more, or about 0.010 inches or more, or about 0.025 inch (about 635 microns) or more, or by about 0.25% or more of an initial crimped diameter of the stent, after being in aqueous condition at about 37 °C in vitro or in vivo for about 1 minute or less, or about 5 minutes or less, or about 15 minutes or less.
  • the stent prior to being balloon-expanded, the stent radially self- expands by about 0.001-0.025 inches, or about 0.003-0.015 inches, or about 0.005-0.10 inches, or about 0.001 inches or more, or about 0.003 inches or more, or about 0.005 inches or more, or about 0.010 inches or more, or about 0.025 inch (about 635 microns) or more, or by about 0.25% or more of the crimped diameter of the stent, after being in aqueous condition at about 37 °C in vitro or in vivo for about 1 minute or less, or about 5 minutes or less, or about 15 minutes or less.
  • the stent is secured in place at least in part from moving at least in one longitudinal direction by about 0.5mm or less, or about 1mm or less, or about 2mm or less, or about 5mm or less, by various means.
  • Such means include at least one of configuring an expandable member proximal and/or distal to the stent, configuring a non expandable member or stops proximal and/or distal to the stent, configuring an attachment or adhesive means adjacent to the stent that does not prevent the stent from being balloon expandable, or configuring a sleeve that ends proximal to the stent, on top of the sent or distal to the stent.
  • the stent constraining means are expandable member proximal and/or distal to the stent and wherein the expandable means is deflated or collapsed at least partially prior to removing the delivery system into the guide.
  • the biodegradable stent comprising a body which comprises a biodegradable copolymer, polymer blends, polymer blocks, polymeric mixtures (with a combination of two or more polymers) wherein suitable copolymers, including the ones described herein, but not limited to the disclosed copolymers, are configured to be capable of being balloon expandable and self expanding, wherein prior to being balloon-expanded, the stent self-expands by about 0.001-0.025 inches, or about 0.003-0.015 inches, or about 0.005- 0.10 inches, or about 0.001 inches or more, or about 0.003 inches or more, or about 0.005 inches or more, or about 0.010 inches or more, or about 0.025 inch (about 635 microns) or more, or by about 0.25% or more of an initial crimped diameter of the stent, after being in aqueous condition at about 37°C in vitro or in vivo for about 1 minute, or about 5 minutes or less
  • the biodegradable implantable devices comprising a polymeric material or body (e.g., a tubular body) , wherein the material has a wet or dry glass transition temperature (T g ) of about 10°C to about 70°C, or about 35°C to about 70°C, or about 40°C to about 60°C, or about 45°C to about 55°C, or about 45°C to about 50°C, or about 37°C to about 70°C, or about 37°C to about 60°C, or about 37°C to about 55°C, or about 37°C to about 50°C, or about 37°C to about 45°C, or greater than 37°C to about 70°C, or greater than 37°C to about 60°C, or greater than 37°C to about 55°C, or greater than 37°C to about 50°C, or greater than 37°C to about 45°C, or greater than 37 °C to less than 45 °C, or greater
  • the one or more materials comprising the body, or the stent, or the stent material, or the tubular body or the polymeric material may have a wet or dry glass transition temperature (T g ) greater than 20°C, or greater than 30°C, or greater than 31°C, or greater than 32°C, or greater than 33°C, or greater than about 34°C, or greater than 35°C, or greater than 36°C, or greater than 37°C.
  • T g wet or dry glass transition temperature
  • the one or more materials comprising the body, or the stent, or the tubular body have a T g less than 45°C, or less than 44°C, or less than 43°C, or less than 42°C, or less than 41°C, or less than 40°C, or less than 39°C, or less than 38°C, or less than 37°C, or less than 36°C.
  • the one or more materials comprising the body, or the stent, or the tubular body have a T g of about 20°C to about 55°C, or about 20°C to about 50°C, or about 31°C to about 45°C, or about 32°C to about 45°C, or about 33°C to about 45°C, or about 34°C to about 45°C, or about 35°C to about 45°C, or about 36°C to about 45°C, or about 37°C to about 45°C, or about 38°C to about 45°C, or about 39°C to about 45°C, or about 40°C to about 45°C.
  • T g of about 20°C to about 55°C, or about 20°C to about 50°C, or about 31°C to about 45°C, or about 32°C to about 45°C, or about 33°C to about 45°C, or about 34°C to about 45°C, or about 35°C to about 45°C, or about 36°C to about 45°C, or about
  • the one or more materials comprising the body, or the stent, or the tubular body have a T g of about 20°C to about 45°C, or about 30°C to about 44°C, or about 30°C to about 43°C, or about 30°C to about 42°C, or about 30°C to about 41°C, or about 30°C to about 40°C, or about 30°C to about 39°C, or about 30°C to about 38°C, or about 30°C to about 37°C.
  • the one or more materials comprising the body, or the stent, or the tubular body has a T g greater than 37°C and less than 45°C, or greater than37°C and less than 40°C, or greater than 37°C to less than 50°C, or greater than 37°C to less than 55°C.
  • the material comprising the body of the device or the biodegradable copolymer or the stent has a degree of crystallinity of about 0% to about 40% and a T g of about or greater than 37°C to about 60°C. In certain embodiments, the material comprising the body of the device or the biodegradable copolymer or the stent has a degree of crystallinity of about 0% to about 30% and a T g of about or greater than 37°C to about 55°C.
  • the material comprising the body of the device or the biodegradable copolymer or the stent has a degree of crystallinity of about 0% to about 30% and a T g of about or greater than 37°C to about 45°C. In certain embodiments, the material comprising the body of the device or the biodegradable copolymer or the stent has a degree of
  • crystallinity of about 0% to about 30% and a T g of about or greater than 10°C to about 35°C.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, or spraying, said biodegradable polymeric material has an initial crystallinity and has a Tg greater than 37°C and the stent prosthesis has a crystallinity (biodegradable stent material) lower than the initial crystallinity and at body temperature is radially expandable and has sufficient strength to support a body lumen.
  • the Tg is greater than 30°C and less than 60°C, preferably greater than 30°C and less than 55°C, preferably greater than 30°C and less than 45°C, more preferably greater than 30°C and less than 40°C, or more preferably greater than 30°C and less than 37°C.
  • the material comprising the body of the device or the biodegradable copolymer or polymer has a glass transition temperature (T g ) of at least about 10 °C, 15 °C, 20 °C, 25 °C, 30 °C, 35 °C, 37 °C, 38 °C, 40 °C, 45 °C, 50 °C, 55 °C, 60 °C, 65 °C or 70 °C.
  • T g glass transition temperature
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer has a T g of about 10 °C, 35 °C, 37 °C or 38 °C to about 70 °C; or about 10 °C, 35 °C, 37 °C or 38 °C to about 65 °C; or about 10 °C, 35 °C, 37 °C or 38 °C to about 60 °C; or about 10 °C, 35 °C, 37 °C or 38 °C to about 55 °C; or about 10 °C, 35 °C, 37 °C or 38 °C to about 50 °C.
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer has a T g of about 35 °C to about 70 °C, or about 45°C to about 60 °C, or about 45 °C to about 55°C. In further embodiments, the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer has a T g of about 10 °C to about 37°C, or about 40°C to about 60°C.
  • the Tg refers to the Tg of the tubular body or the polymeric material in a pellet form or after forming the tubular body or before treatment(s) or after treatment(s) or prior to implantation.
  • said heating can be at about Tg or below Tg, and the treatment(s) is prior to patterning or after patterning.
  • the heat treatment or modification can be during patterning, such as during laser patterning.
  • the Tg refers to the Tg of the tubular body or the polymeric material as a pellet or after forming the tube, or the Tg is measured prior to the treatment or modification, or the Tg is measured after the treatment or modification, or the Tg is measured prior to implantation.
  • Tg it is desired to control Tg to a desired range from 30°C to 60°C, preferably 35°C to 55°C, more preferably from 37°C to 50°C, more preferably greater than 37°C to 50°C.
  • This allows for fabrication of a stent prosthesis capable of radial expansion at body temperature, or above body temperature, or below body temperature.
  • Examples of controlling Tg can be accomplished through additives such as plasticizers and monomers, presence or addition of solvents (such water, DCM, ethanol), and radiation.
  • Controlling Tg (e.g., increasing it) can be accomplished by heating the material (below Tg, Tg, or above Tg), pressurizing the material, removing additives or platicizers or solvents, and sometimes (depending on the material) through radiation. Control of radiation, increase or decrease or maintaining it, from substantially maintaining it the same from after forming to prior to implant, or increasing it from forming to prior to implant, or decreasing it from forming to prior to implant.
  • Tg changes ranging from 0% change in Tg to 100% change in Tg, preferably from 5% to 50%, and more preferably 10% to 25%.
  • Tg changes by at least 0% from initial Tg, or by at least 10% of the initial or original Tg, and more preferably Tg changes by at least 25% of the original Tg.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, or spraying, said biodegradable polymeric material has been treated to control Tg to between 35°C to 55°C, and the stent prosthesis at body temperature is radially expandable and has sufficient strength to support a body lumen.
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable polymer or copolymer has a melting enthalpy (AH m ) of about 7 J/g to about 50 J/g, or about 7 J/g to about 45 J/g, or about 7 J/g to about 40 J/g, or about 20 J/g to about 45 J/g, or about 20 J/g to about 40 J/g, or about 20 J/g to about 35 J/g, or about 25 J/g to about 35 J/g.
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer or polymer has a AH m of about 7 J/g to about 50 J/g.
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer or polymer has a crystallization enthalpy (AH C ) less than about 5 J/g, or less than about 3 J/g, or less than about 1 J/g, or of about 0 J/g, during first heating.
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer or polymer has a crystallization enthalpy less than about 5 J/g, or less than about 3 J/g, or less than about 1 J/g, or of about 0 J/g, during first cooling.
  • the material e.g., polymeric material
  • the material comprising the body of the device or the biodegradable copolymer or polymer has a AH C less than about 5 J/g during first heating and a AH C less than about 5 J/g during first cooling.
  • the treatment(s) of the biodegradable polymeric material controls maintaining crystallinity to be substantially the same.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, or spraying, said biodegradable polymeric material has an initial crystallinity and has a Tg greater than 37°C, and the stent prosthesis has a crystallinity (biodegradable stent material) that is substantially the same as the initial crystallinity and at body temperature is radially expandable and has sufficient strength to support a body lumen.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, or spraying, said biodegradable polymeric material has an initial crystallinity and has a Tg greater than 37°C, and the stent prosthesis has a crystallinity (biodegradable stent material) lower than the initial crystallinity and at body temperature is radially expandable and has sufficient strength to support a body lumen.
  • the Tg is greater than 30°C and less than 60°C, preferably greater than 30°C and less than 55°C, preferably, greater than 30°C and less than 45°C, more preferably greater than 30°C and less than 40°C, or more preferrably greater than 30°C and less than 37°C.
  • a measure of residual/internal stress in a polymeric article or a device is shrinkage of the polymeric article or the device in a direction (e.g., longitudinal direction and/or radial direction) over a period of time when the polymeric article or the device is heated over that period of time at about the T g or above the T g or below the T g of the material comprising the polymeric article or the body of the device.
  • a direction e.g., longitudinal direction and/or radial direction
  • a tube comprised of a biodegradable polymeric material or a stent formed from such a tube exhibits shrinkage in length of no more than about 25%, 20%, 15%, 10% or 5%, and/or shrinkage in diameter of no more than about 25%, 20%, 15%, 10% or 5%, over a period of time (e.g., about 0.1, 12, 24, 48 to about 72 hours) when the tube or the stent is heated over that period of time at about the T gi or above T g , or below T g (e.g., about 5°C, 10°C, 20°C or 30°C above) the T g of the polymeric material comprising the tube or the stent body, or (e.g., about 5°C,10°C, 20°C, or 30°C) below the T g of the polymeric material comprising the tube or the stent body.
  • T gi or above T g or below T g (e.g., about 5°C, 10°C, 20°C
  • a tube comprised of a biodegradable polymeric material or a stent formed from such a tube exhibits shrinkage in length of no more than about 10% or 5%, and/or shrinkage in diameter of no more than about 10% or 5%, over a period of time (e.g., about 1, 12, or 24 hours) when the tube or the stent is heated over that period of time at about the T g or above (e.g., about 10°C or 20°C to about 30°C above) the T g , or below Tg (e.g., about 5°C, 10°C, to about 3°0 C below T g of the polymeric material comprising the tube or the stent body.
  • T g or above e.g., about 10°C or 20°C to about 30°C above
  • Tg e.g., about 5°C, 10°C, to about 3°0 C below T g of the polymeric material comprising the tube or the stent body.
  • the biodegradable stent comprising a body which comprises a biodegradable copolymer, polymer blends, polymer blocks, polymeric mixtures (with a combination of two or more polymers) wherein suitable copolymers, including the ones described herein, but not limited to the disclosed copolymers, are configured to be capable of balloon expandable and self expanding, wherein prior to being balloon-expanded, the stent radially self-expands by about 0.001-0.025 inches, or about 0.003-0.015 inches, or 0.005-0.10 inches, or about 0.001 inches or more, or about 0.003 inches or more, or about 0.005 inches or more, or about 0.010 inches or more, or about 0.025 inch (about 635 microns) or more, or by about 0.25% or more of an initial crimped diameter of the stent, after being in aqueous condition at about 37 °C in vitro or in vivo for about lminute or less, or about
  • the stent self expands to a diameter that is less than the final intended deployment diameter of the stent prior to being balloon expanded to the final intended deployment diameter after being in aqueous condition at about 37°C in vitro or in vivo for about 1 minute or less, or about 5 minutes or less, or about 15 minutes or less.
  • the properties described herein with respect to the material such as inherent viscosity, tensile strength, percent elongation at break or yield, and ductility are in the ranges stated prior to deployment of the stent, or after deployment of the stent.
  • a partially self-expandable stent can be retained on a balloon-catheter by any suitable means, including any means described herein. Such a stent can be restrained from
  • the sheath or other constraining means can be withdrawn or removed to allow the stent to radially self- expand prior to balloon-expansion to an intended deployment diameter.
  • Partial self-expansion of a stent can be promoted or controlled by any of a variety of ways.
  • the body of the stent can be comprised of a polymeric material that has a T g closer to but above body temperature.
  • the stent polymeric material having a T g closer to but above body temperature can control self-expansion of the stent. Having some differentiation between the T g of the stent polymeric material and body temperature can prevent self-expansion of a crimped stent that has some memory of the larger diameter of the polymeric tube from which it was patterned, as soon as the stent reaches body temperature.
  • Water permeability of the polymeric material comprising the stent body can promote self- expansion of the stent, as water absorption into the stent body can cause the stent to swell and self-expand.
  • Coating the stent with a material that is more crystalline or reduces water absorption, or incorporating an additive in the coating of the stent which reduces water absorption or reacts with water, can control self-expansion of the stent.
  • exposing the crimped stent to low heat can control self- expansion of the stent when in aqueous condition at about 37 °C in vitro or in vivo.
  • the biodegradable stent is capable of being crimped to, e.g., inner (luminal)] diameter of about 0.5 mm to about 4 mm, or about 1 mm to about 2 mm, or about 1.2 mm to about 1.6 mm, or about 1.3 mm to about 1.5 mm, and is capable of being radially expanded, e.g., in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37 °C in vitro or in vivo, to a (e.g., inner) diameter of about 2 mm to about 8 mm, or about 2 mm to about 6 mm, or about 2 mm to about 4 mm, or about 2.5 mm to about 4 mm, or about 2.7 mm to about 3.8 mm, or about 3 mm to about 3.6 mm, without substantial damage to struts, crowns or links of the stent, or without
  • the stent is capable of being crimped to a (e.g., inner) diameter of about 1.2 mm to about 1.6 mm and is capable of being radially expanded, e.g., in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37 °C in vitro or in vivo, to a (e.g., inner) diameter of about 2.5 mm to about 4 mm without substantial damage to struts, crowns or links or without substantial recoil, or both.
  • aqueous condition e.g., in aqueous solution, water, saline solution or physiological conditions
  • the biodegradable stent is capable of being radially expanded, e.g., in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37 °C in vitro or in vivo, to an initial deployment diameter and then to a second deployment diameter that is about 1% to about 300%, or about 10% to about 300%, or about 10% to about 100%, or to a greater than the initial deployment diameter, wherein the stent is uniformly expanded; or without substantial damage and/or without fracture/breakage to struts, crowns or links of the stent or/and without substantial recoil; or at least some.
  • aqueous condition e.g., in aqueous solution, water, saline solution or physiological conditions
  • the biodegradable stent is capable of being radially expanded to an intended deployment diameter, e.g., in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37 °C in vitro or in vivo with about 50% or less of crowns of the stent having a crack length of about 50% of the local crown width or shorter, or about 40% or less of the crowns having a crack length of about 40% of the local crown width or shorter, or about 30% or less of the crowns having a crack length of about 30% of the local crown width or shorter, or about 25% or less of the crowns having a crack length of about 25% of the local crown width or shorter, or about 20% or less of the crowns having a crack length of about 20% of the local crown width or shorter, or about 10% or less of the crowns having a crack length of about 10% of the local crown width or shorter, or about 5% or less of the crowns having a crack length of about 5% of the local crown width
  • the stent is capable of being radially expanded to an intended deployment diameter, e.g., in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37 °C in vitro or in vivo, with about 25% or less of the crowns having a crack length of about 25% of the local crown width or shorter.
  • the stent is capable of being deployed to an expanded diameter ranging from about 2mm to about 4mm in aqueous environment at 37 °C without breakage (fracture) in any of the struts, crowns, or links.
  • the stent prosthesis is capable of uniform radial expansion to an intended diameter from a crimped state without cracks, or without fracture/breakage in any of the links, struts, or crowns.
  • Cracking or fracture of a structure can be analyzed by any suitable method known in the art, including without limitation by visualization using a microscope, optical comparator or scanning electron microscope.
  • Cracking or fracture of a biodegradable polymeric stent can be reduced by any of a variety of ways.
  • Additional treatment, design, or control of material properties include: making the body of the stent from a polymeric material that is ductile and tough under physiological conditions can reduce cracking of the stent.
  • Water permeability of the stent polymeric material can also reduce cracking (and improve radial strength) of the stent. When water permeates into the stent body, it can swell the polymeric material of the body, which can reduce the brittleness of the polymeric material.
  • the stent can have a longer radius of curvature. Moreover, minimizing exposure of the crimped stent to heat (in terms of, e.g., temperature and exposure time), as described herein with respect to reducing recoil, can decrease cracking of the stent.
  • the stent is at least partially configured to radially self expand to decrease cracking or breakage of struts, crowns, or links upon deployment of the stent.
  • the conditions and manner in which the stent is radially expanded can also affect cracking (and radial strength and recoil) of the stent.
  • Other means of reducing cracking include without limitation allowing the stent to reach approximately body temperature, or within about 2°C to about 25°C of body temperature, prior to balloon radial expansion, and/or allowing time (e.g., at least about 0.1, 0.25, 0.5, 1, 2, 3, 4 or 5 minutes) for the stent to heat or/and absorb water into the stent prior to balloon radial expansion.
  • cracking or fracture can be decreased by radially expanding the stent substantially uniformly such that crowns of the stent open at a substantially similar angle, or within 50 degrees of one another.
  • cracking or fracture can be reduced by maintaining a balloon-expanded stent at the radially expanded state with the balloon inflated for a longer time (e.g., at least about 0.1, 0.25, 0.5, 1, 2, 3, 4 or 5 minutes), and/or using a stent-delivery catheter (e.g., LifestreamTM catheter from Abbott) that allows blood to flow through while the balloon is inflated for a longer time (e.g., about 1, 3 or 5 or more minutes).
  • a stent-delivery catheter e.g., LifestreamTM catheter from Abbott
  • a slow rate of inflation of the balloon in the beginning of balloon-assisted expansion can reduce cracking.
  • a 3 mm stent can be deployed (radially expanded to the intended deployment diameter) by inflation of the balloon to about 6 to 16 atmospheres of pressure.
  • the rate of inflation of the balloon can be about 2 or 5 to about 20 seconds per atmosphere, or about 7 to about 15 seconds per atmosphere.
  • the balloon can be inflated at a faster rate (e.g., about 0.1 to about 5 seconds per atmosphere).
  • the pressure of the balloon can be maintained for a period of time, e.g., for at least about 0.1, 0.25, 0.5, 1, 2 or 3 minutes.
  • a stent-delivery catheter e.g., LifestreamTM catheter
  • LifestreamTM catheter that allows blood to flow through while the balloon is inflated
  • Exposure of the stent to a temperature substantially equal to or above body temperature prior to and/or during radial expansion can also decrease cracking or fracture of the stent.
  • the stent prior to and/or during radial expansion the stent is exposed to a temperature at least about 1 °C, 4 °C, 8 °C, 12 °C or 16 °C above body temperature, or to a temperature within about 20 °C, 15 °C, 10 °C or 5 °C of the T g (below or above the T g ), or equal to or above the T g , of the material (e.g., polymeric material) comprising the body of the stent.
  • the material e.g., polymeric material
  • Exposure of the stent to a temperature substantially equal to or above body temperature can be accomplished by any of a variety of means, such as use of a heating coil or element(s) in the balloon, use of heating element(s) on the surface of the balloon or the proximal shaft of the delivery catheter, heating of a liquid inside the balloon, introduction of a heated liquid into the balloon, or introduction of a heated aqueous (e.g., saline) solution into the bodily fluid (e.g., blood stream) at the site of stent deployment.
  • a heating coil or element(s) in the balloon use of heating element(s) on the surface of the balloon or the proximal shaft of the delivery catheter, heating of a liquid inside the balloon, introduction of a heated liquid into the balloon, or introduction of a heated aqueous (e.g., saline) solution into the bodily fluid (e.g., blood stream) at the site of stent deployment.
  • a heated aqueous e.g.,
  • fatigue of a stent is measured by the appearance of a certain number of pieces (e.g., one piece) missing from the stent, or the appearance of a certain number of fractures (e.g., two fractures), or the appearance of a certain number of cracks (e.g., three cracks), optionally under certain conditions, e.g., in dry condition or in aqueous condition (e.g., aqueous solution, water, saline solution or physiological conditions) at a certain temperature (e.g., ambient temperature or about 37 °C) in vitro or in vivo, and optionally over a certain period of time (e.g., about 1 minute to about 1, 2 or 3 weeks, or about 1, 2, 3, 4, 5 or 6 months).
  • a certain number of pieces e.g., one piece
  • fractures e.g., two fractures
  • a certain number of cracks e.g., three cracks
  • a certain number of cracks e.g., three cracks
  • a crack is cracking that does not extend through the whole width of a crown
  • a fracture is cracking that extends through the whole width or depth of a crown, strut, or a link, therby breaking the crown, strut, or link.
  • fatigue of a stent is measured based on the number of cycles (or the number of months of fatigue) before the appearance of a certain number of pieces (e.g., one piece) missing from the stent.
  • Fatigue testing can be conducted under real-time or accelerated condition.
  • the stent can be subjected to a cyclic loading of, e.g., about 1 to 2 Hz (about 60 to 120 cycles per minute, substantially similar to a human heart beat).
  • the test can be conducted for about 1, 2 or 3 months or longer to simulate the time period of implantation in a subject.
  • the stent can be tested in vitro in a tube that has a radial compliance of, e.g., about 3% to 5% (the tube could radially expand by about 3% to 5%), which is substantially similar to the compliance of an artery. Under accelerated condition, the stent can be subjected to a cyclic loading greater than about 2 Hz (e.g., about 30 Hz). At 30 Hz, it would take about 6 days of continuous cycling, compared to about 90 days at 2 Hz, to attain about 3 months of fatigue.
  • the stent does not exhibit missing pieces or complete fracture of a link, a strut, or a crown after fatigue testing at one of the above conditions from about 1 day to about 6 months, or from about one week to about one month or from about 2 weeks to about 3 months.
  • Resistance of a stent to fatigue can be enhanced by any of a variety of ways.
  • fatigue resistance/strength can be increased by making the stent from a polymeric material that is ductile and tough under physiological conditions, and/or by configuring the stent to be capable of radially self-expanding prior to balloon expansion to an intended deployment diameter.
  • fatigue resistance/strength can be increased by making the stent from a polymeric material that is ductile and tough under physiological conditions, and/or by configuring the stent to be capable of radially self-expanding prior to balloon expansion to an intended deployment diameter.
  • fatigue resistance/strength can be increased by making the stent from a polymeric material that is ductile and tough under physiological conditions, and/or by configuring the stent to be capable of radially self-expanding prior to balloon expansion to an intended deployment diameter.
  • fatigue strength can be enhanced by any of a variety of ways.
  • fatigue resistance/strength can be increased by
  • resistance/strength can be enhanced by the pattern or design of the stent, by decreasing the sharpness (or increasing the smoothness) of edges of crowns of the stent, and/or by increasing the uniformity of the cross-section of the crowns.
  • fatigue As a further example, fatigue
  • resistance/strength can be increased by minimizing exposure of the stent to extremely high temperature or extremely low temperature, and/or by minimizing bending and other stresses on the stent (e.g., when the stent is at, below or above body temperature).
  • the biodegradable stent has a radial strength of at least about 5,
  • the stent has a radial strength of about 5 psi to about 30 psi, or about 5 psi to about 25 psi, or about 10 psi to about 25 psi, or about 12 psi to about 23 psi, or about 10 psi to about 20 psi, or about 15 psi to about 20 psi, or about 16 psi to about 22 psi, in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37 °C in vitro or in vivo.
  • aqueous condition e.g., in aqueous solution, water, saline solution or physiological conditions
  • the stent has a radial strength of about 5 psi to about 30 psi, or about 10 psi to about 25 psi, in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37 °C in vitro or in vivo.
  • aqueous condition e.g., in aqueous solution, water, saline solution or physiological conditions
  • Radial strength of a biodegradable polymeric stent can be improved in any of a variety of ways. As an example, making the stent body from a polymeric material that is ductile and tough under physiological conditions can enhance the radial strength of the stent. Further, radial strength can be increased by orienting the stent polymeric material, or the crystals, crystalline regions or chains of the polymeric material, substantially in the circumferential direction.
  • the tube prior to patterning the stent from a polymeric tube, the tube can be radially expanded, optionally while the tube is heated at elevated temperature (e.g., at or above the T g of the tube polymeric material) and optionally with cooling of the radially expanded tube to a lower temperature (e.g., below T g ), to impart substantially circumferential orientation or biaxial (neither preferentially circumferential nor preferentially longitudinal) orientation to the polymeric material, or its crystals, crystalline regions or polymer chains. Crimping the stent to a smaller diameter under certain conditions can minimize radial strength loss upon expansion of the stent.
  • the stent is crimped gradually at a temperature ranging from about 25°C to about 50°C in 10 seconds to about 10 minutes.
  • the conditions and manner in which the stent is radially expanded can also affect the radial strength of the stent.
  • Non-limiting conditions and ways in which the stent can be radially expanded to improve radial strength are described with respect to reducing cracking or improving stent expanded uniformity.
  • the biodegradable stent exhibits a percentage radially inward recoil of about 15% or less, or about 12% or less, or about 10% or less, or about 8% or less, or about 6% or less, or about 5% or less, or about 4% or less, or about 3% or less, after a period of time (e.g., about 1, 3 or 5 days, or about 1, 2 or 3 weeks, or about 1, 2 or 3 months) after being radially expanded to an intended deployment diameter in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37°C in vitro or in vivo.
  • aqueous condition e.g., in aqueous solution, water, saline solution or physiological conditions
  • the stent exhibits a percentage radially inward recoil of about 10% or less, or about 8% or less, about one week to about one month after being radially expanded to an intended deployment diameter in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37 °C in vitro or in vivo.
  • aqueous condition e.g., in aqueous solution, water, saline solution or physiological conditions
  • Recoil of the stent can be reduced by any of a variety of ways.
  • the body of the stent can be comprised of a polymeric material that is ductile and tough under physiological conditions, has a T g that is not too high (e.g., about 60 °C, 55 °C, 50 °C or lower), and/or has a molecular weight of at least a certain value (e.g., a weight-average molecular weight of at least about 120 kDa, 150 kDa, 180 kDa, 210 kDa, 240 kDa, 500kDa, or 900 kDa).
  • recoil of a stent comprised of a polymeric material having molecular weight in the range of about 120 kDa to about 1200 kDa is less than 10% as a result of greater entanglement of longer polymer chains. In some embodiments, the recoil of a stent comprised of a polymeric material having molecular weight in the range of about 120kDa to about 1200 kDa is less than 10% as a result of greater entanglement of longer polymer chains. Greater entanglement of polymer chains can further reduce recoil of the polymeric tubular body having higher molecular weight.
  • a stent is designed to have reduced recoil by being configured to be fully self-expandable or be capable of radially self-expanding (e.g., by at least about
  • the body of a partially self-expandable stent is comprised of a polymeric material that has a T g of about 35 °C to about 55 or 60 °C, or about 37 °C to about 55 or 60 °C, or about 40 °C to about 50 or 55 °C, or about 45 °C to about 50 or 55 °C.
  • the stent is exposed to a temperature within about 15 °C, 10 °C, 5 °C or 3 °C of the T g (below or above the T g ), or at or above the T g .
  • the body of a fully self-expandable stent or a partially self-expandable stent is comprised of a polymeric material that has a T g of about 10 °C to about 35 or 37 °C, or about 15 °C to about 35 or 37 °C, or about 20 °C to about 30 or 35 °C, or about 25 °C to about 30 or 35 °C.
  • a partially or fully self-expandable stent is patterned from a polymeric tube having a diameter greater than an intended deployment diameter or the maximum allowable expansion diameter of the stent, as described herein.
  • Recoil of a biodegradable stent can also be reduced by patterning the stent from a polymeric tube having a diameter (e.g., inner diameter) that is slightly smaller, same, or greater than (e.g., at least about -10%, -5%, 0%, 5%, 10%, 20%, 30%, 40% or 50%) the intended deployment (e.g., inner) diameter or the maximum allowable expansion (e.g., inner) diameter of the stent.
  • a diameter e.g., inner diameter
  • the intended deployment e.g., inner
  • the maximum allowable expansion e.g., inner
  • the stent After deployment in aqueous condition at about 37 °C, the stent can have a tendency or ability to self-expand over time to the larger diameter of the tube from which the stent was cut if the stent is exposed to a temperature equal to or above the T g of the polymeric material comprising the stent body.
  • the T g of a polymeric material in aqueous condition (wet T g ) can be lower (e.g., about 1-5 °C lower, or about 1-10 °C lower, or about 1- 15 °C lower, or about 5 °C, 10 °C or 15 °C lower) than its dry T g .
  • the stent's tendency or ability to self-expand to the larger tube diameter can minimize or prevent radially inward recoil of the stent after deployment.
  • recoil can be reduced by crimping the stent at a temperature at about the T g or below the T g (e.g., at least about 1 °C, 5 °C, 10 °C, 15 °C, 20 °C, 25 °C, 30 °C, or 35 °C below the T g ) of the material (e.g., polymeric material) comprising the stent body.
  • the material e.g., polymeric material
  • Minimizing exposure of the crimped stent to heat can also reduce recoil (and reduce cracking and improve radial strength).
  • Heat may promote generation of a crimped-state memory and may promote erasure of some amount of the as-cut tube memory (the diameter of the tube used to pattern the stent).
  • recoil can be decreased by exposing the crimped stent to a temperature not exceeding the T g , or at least about 1 °C, 5 °C, 10 °C, 15 °C, 20 °C, 25 °C or 30 °C below the T g , of the material (e.g., polymeric material) comprising the stent body during, e.g., stabilization of the stent in the crimped state, mounting of the crimped stent onto a balloon-catheter, sterilization of the stent delivery system (e.g., with e-beam), and storage.
  • the material e.g., polymeric material
  • the conditions and manner in which the stent is radially expanded can also affect recoil of the stent.
  • Non-limiting conditions and ways in which the stent can be radially expanded to reduce recoil are described with respect to reducing cracking.
  • the biodegradable stent exhibits reduction in length of no more than about 25%, 20%, 15%, 10% or 5% after a period of time (e.g., about 1, 3 or 5 days, or about 1, 2 or 3 weeks, or about 1, 2 or 3 months) after being radially expanded to an intended deployment diameter in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37 °C in vitro or in vivo.
  • a period of time e.g., about 1, 3 or 5 days, or about 1, 2 or 3 weeks, or about 1, 2 or 3 months
  • the biodegradable stent exhibits reduction in length of no more than about 10% about one week to about one month after being radially expanded to an intended deployment diameter in aqueous condition (e.g., in aqueous solution, water, saline solution or
  • the biodegradable stent comprising a body which comprises a biodegradable polymer, or copolymer, polymer blends, polymer blocks, polymer mixture wherein the polymer material is configured to be capable of being balloon expandable and self expanding, wherein prior to being balloon-expanded, the stent self-expands by about 0.001-0.025 inches, or about 0.003- 0.015 inches, or about 0.005-0.10 inches, or about 0.001 inches or more, or 0.003 inches or more, or 0.005 inches or more, or 0.010 inches or more, or 0.025 inch or more, or by about 0.25% or more of an initial crimped diameter of the stent, after being in aqueous condition at about 37 °C in vitro or in vivo for about 1 minute, or about 5 minutes or less, or about 15 minutes or less.
  • the biodegradable stent comprising a body which comprises a biodegradable copolymer or polymer, or mixture of 2-3 polymers, or blend of polymers, or wherein the copolymer or polymer is configured to be capable of balloon expandable and self expanding, wherein prior to being balloon-expanded, the stent radially self-expands by about 0.001-0.025 inches, or about 0.003-0.015 inches, or 0.005-0.10 inches, or about 0.001 inches or more, or about 0.003 inches or more, or about 0.005 inches or more, or about 0.010 inches or more, or about 0.025 inch or more, or by about 0.25% or more of an initial crimped diameter of the stent, after being in aqueous condition at about 37 °C in vitro or in vivo for about Iminute or less, or about 5 minutes or less, or about 15 minutes or less, and wherein the stent or the stent body has one or more of the following properties
  • the biodegradable stent comprising a body which comprises a biodegradable copolymer or polymer, wherein the copolymer or polymer is configured to be balloon expandable and self expanding, wherein prior to being balloon-expanded, the stent radially self-expands by about 0.025-0.25inches, or about 0.50-0.15 inches, or about 0.025 inches or more, or about 0.050 inches or more, or about 0.1 inches or more, or by about
  • the stent is constrained from self expanding using a sheath or other means and then such constraining means is removed, disengaged, or withdrawn, or released after the stent is positioned for deployment, allowing the stent to self deploy.
  • the material comprising the body of the device or the biodegradable polymer, copolymer or polymer blend, or the tubular body comprising the biodegradable polymer, or the stent is, or has crystals, crystalline regions, or polymer chains that are: substantially not uniaxially oriented, or circumferentially oriented, or longitudinally oriented, or biaxially oriented.
  • the biodegradable copolymer has crystals, crystalline regions, molecular architecture, structural order, orientation, or polymer chains that are: substantially not uniform, or has low degree of order, or has varying degree of order, or is not substantially oriented as a result of not performing at least one of pressurizing and stretching of the tubular body, or is at least partially oriented as a result of spraying or dipping or crystallization or recrystallization, or radiation, or is at least partially oriented as a result of solvent evaporation or annealing or radiation, or is substantially not oriented, or not uniformly oriented, or low order oriented, or varying degree oriented, or randomly oriented, as a result of spraying or dipping, or solvent evaporation, or annealing, or radiation, or crystallization or recrystallization.
  • the biodegradable copolymer has crystals, crystalline regions, molecular architecture, structural order, orientation, or polymer chains that are: substantially oriented, or oriented, or biaxially oriented, or uniaxially oriented, or oriented in a direction that is longitudinal, or oriented in a direction that is circumferential, or oriented in a direction that is not longitudinal or circumferential, or oriented as a result of at least one of pressurizing the copolymer tube or stretching or drawing the tube, or oriented as a result of modification or treatment.
  • the material comprising the body of the device or the biodegradable polymer, or copolymer or polymer blend, or the tubular body comprising the biodegradable polymer has a tensile strength of at least about 2000 psi, or at least about 2500 psi, or at least about 3000 psi, or at least about 4000psi, or 5000 psi.
  • the biodegradable polymeric material or the tubular body or the stent has stiffness of at least lOOOMPa, or at least 1500MPa, or at least 2000MPa, or at least 2500MPa, or at least 3000MPa, or at most 5000MPa, or at most 4000MPa; when measured at ambient or body temperature.
  • the biodegradable polymeric material or the tubular body or the stent has elastic modulus of at least 250MPa, or at least 350MPa, or at least 400MPa, or at least 450MPa, or at least 500MPa; when measured at ambient or body temperature
  • the material comprising the body or the biodegradable polymer or copolymer or polymer blend, or the tubular body comprising the biodegradable polymer, or the stent has a percent elongation at break of about 20% to about 600%, or of about 20% to about 300%, or of about 20% to about 200%, or of about 20% to about 100%, or of about 20% to about 50%, or of about 10% to about 600%, or of about 10% to about 300%, or of about 5% to about 600%, or of about 5% to about 300%, or of about 1% to about 600%, or of about 1% to about 300%, or of about 1% to about 200%, or of about 1% to about 150%; when measured we
  • the biodegradable polymer, copolymer or polymer blend or tubular body comprising the biodegradable polymer material or prosthesis has stiffness dry or wet at about 37°C of about 0.4N/mm2 to about 2N/mm2, or of about 0.5N/mm2 to about 1.5N/mm2, or of about 0.7N/mm2 to about 1.4N/mm2, or of about 0.8N/mm2 to about 1.3N/mm2.
  • the biodegradable polymer or copolymer or polymer blend or tubular body comprising the biodegradable polymer material or prosthesis has elastic modulus dry or wet at about body temperature, of about 0.2Pa to about 20Pa, or of about 0.3Pa to about 5Pa, or of about 0.4 to about 2.5Pa, or of about 0.5Pa to about lPa, or at least 0.2Pa, or at least 0.3Pa, or at least 0.4Pa, or at least 0.5Pa.
  • the biodegradable polymer or copolymer or polymer blend or tubular body comprising the biodegradable polymer material or prosthesis has yield strain of at most 15%, preferably at most 10%, more preferably at most 5%, in water at 37°C.
  • the prosthesis has radial strength sufficient to support a body lumen.
  • the biodegradable polymer or copolymer or tubular body or prosthesis has a radial strength in an aqueous environment at about 37°C of about 3psi to about 25psi, or of about 5psi to about 22 psi, or of about 7psi to about 20psi, or of about 9psi to about 18 psi.
  • the biodegradable polymer or copolymer or tubular body or prosthesis has a radial strength in an aqueous environment at body temperature of, greater than 3psi, or greater than 8psi, or greater than lOpsi, or greater than 15psi.
  • Radial strength can be measured in a variety of methods known in the art. For example the flat plate method or iris method or other known methods. Radial force can be measured with several methods known in the art. For example when the stent radial strength is not sufficient to support a body lumen, or the expanded diameter is reduced by a substantial amount, or reduced by at least 15%, or reduced by at least 20%, or reduced by at least 25%, or reduced by at least 50%.
  • the biodegradable copolymer, or polymer blend, or polymer, or tubular body comprising the biodegradable polymer, or prosthesis has a % recoil in an aqueous environment at 37°C of about -20% to about 20%, or of about-15% to about 15%, or of about -10% to about 10%, or of about -10% to about 0%, or of about 3% to about 10%, or of about 4% to about 9%, or less than 25%, or less than 20%, or less than 15%, or less than 10%, or less than 5%; after expansion from a crimped state.
  • % recoil is measured in a variety of ways in-vitro or in- vivo with methods known in the art.
  • in-vitro % recoil can be measured by expanding the stent in an aqueous environment at about 37 °C inside a tube or unconstrained and measuring % recoil after expansion using laser micrometer.
  • in- vivo % recoil measurement using QCA see, e.g., Catheterization and Cardiovascular Interventions, 70:515-523 (2007).
  • the biodegradable polymer or copolymer or tubular body or prosthesis has a radial strength (in an aqueous environment at 37°C for about 1 minute to about lday) of about 3psi to about 25psi; wherein the radial strength increases by about lpsi to about 20psi, or by about 2psi to about 15psi, or by about 3psi to about lOpsi, or by about 4psi to about 8 psi, after being in such an aqueous environment for about 1 day to about 60 days.
  • the biodegradable, polymer, or copolymer, or polymer blend, or tubular body, or stent is substantially amorphous, or substantially semi crystalline, or substantially crystalline; after modification, or before modification, or after radiation, or before implantation into a mammalian body.
  • the biodegradable polymer, or copolymer or polymer blend, or tubular body, or stent is substantially amorphous before and after modification, or substantially amorphous before a modification and substantially semi crystalline after modification, or substantially amorphous before a modification and substantially crystalline after modification, or substantially semi crystalline before a modification and substantially amorphous after modification, or substantially semi crystalline before a modification and substantially semi crystalline after modification, or substantially semi crystalline before a modification and crystalline after modification, or substantially crystalline before modification and substantially semi crystalline after a modification, or substantially crystalline before modification and substantially semi crystalline after a modification, or substantially crystalline before a modification and substantially amorphous after a modification, or substantially crystalline before a modification and after modification.
  • the biodegradable polymer or copolymer or polymer blend or tubular body or implant has longitudinal shrinkage of about 0% to about 30%, or of about 5% to about 25%, or of about 7% to about 20%, or of about 10% to about 15%; when heated (e.g. in an oven) at temperatures ranging from about 30°C to about 150°C (with or without a mandrel inserted into the copolymer or tubular body or prosthesis for a time ranging from about 30 minutes to about 24 hours), or upon expansion of the stent from a crimped state to an expanded state.
  • the longitudinal shrinkage is less than 30%, or less than 25%, or less than 20%, or less than 15%, or less than 10%, of the original length.
  • the stent or polymer material or polymer tube has longitudinal shrinkage of less than about 25% or less, or about 15% or less, or about 10% or less, or about 5% or less, or about 1-25%, or about 5-15%, after being in aqueous condition at about 37 °C in vitro or in vivo for about 1 minute or less, or about 5 minutes or less, or about 15 minutes or less, or after expansion from the crimped state.
  • the stent or polymer material or polymer tube has longitudinal shrinkage of less than about 25% or less, or about 15% or less, or about 10% or less, or about 5% or less, or about 1-25%, or about 5-15%, after being in aqueous condition at about 37°C in vitro or in vivo for about 1 minute or less, or about 5 minutes or less, or about 15 minutes or less, or after expansion from the crimped state by configuring the polymer to be; more amorphous, or substantially amorphous, or reducing internal stresses, or reducing or minimizing orientation of the polymer, and/or optimizing design of the stent, or a combination thereof.
  • the amorphous, or semicrystalline, or crystalline polymer has internal stresses, or longitudinal shrinkage of no more than 15% from before a modification to after modification.
  • the polymer comprises a polymer, or a co-polymer, or a blend of polymers, or a mixture of polymers, or a blend of polymer and at least one monomer, or a blend of co-polymer and at least one monomer, or a combination thereof.
  • the polymer blend, copolymer, or mixture of polymers substantially does not exhibit phase separation.
  • the polymer or tubular body or prosthesis is porous; such that it will grow in the radial direction by about 0.025mm to about 1mm when soaked in an aqueous environment at 37°C from about 1 minute to about 15 minutes.
  • the copolymer material, or tubular body, or prosthesis has a textured surface, or non uniform surface, or surface with ridges, or bumpy surface, or surface with grooves, or wavy surface. The distance between the peak and trough of the surface texture ranges from about 0.01 micron to about 30 micron, or from about 0.1 micron to about 20 micron, or from about 1 micron to about 15 micron.
  • the yield strength of the material (e.g., polymeric material) comprising the body of an endoprosthesis (e.g., a stent) is at least about 50%, 60%, 70%, 75%, 80%, 90% or 95% of ultimate strength in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37 °C in vitro or in vivo.
  • aqueous condition e.g., in aqueous solution, water, saline solution or physiological conditions
  • the yield strength of the material (e.g., polymeric material) comprising the body of the endoprosthesis (e.g., stent) is at least about 75% of ultimate strength in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37 °C in vitro or in vivo.
  • the elastic modulus of the material (e.g., polymeric material) comprising the body of an endoprosthesis (e.g., a stent) is at least about 0.1, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9 or 10 GPa in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37 °C in vitro or in vivo.
  • aqueous condition e.g., in aqueous solution, water, saline solution or physiological conditions
  • the elastic modulus of the material (e.g., polymeric material) comprising the body of the endoprosthesis (e.g., stent) is at least about 0.5 or 0.75 GPa in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37 °C in vitro or in vivo.
  • the elastic recovery of a strained material comprising the body of an endoprosthesis (e.g., a stent) is at most about 20%, 18%, 16%, 15%, 14%, 12%, 10%, 8%, 6%, 5%, 4% or 2% in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37 °C in vitro or in vivo.
  • the elastic recovery of a strained material comprising the body of the endoprosthesis (e.g., stent) is at most about 15% or 10% in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37 °C in vitro or in vivo.
  • a strained material e.g., polymeric material
  • aqueous condition e.g., in aqueous solution, water, saline solution or physiological conditions
  • the yield strain of the material (e.g., polymeric material) comprising the body of an endoprosthesis (e.g., a stent) is at most about 15%, 14%, 12%, 10%, 8%, 6%, 5%, 4%, 3% or 2% in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37 °C in vitro or in vivo.
  • aqueous condition e.g., in aqueous solution, water, saline solution or physiological conditions
  • the yield strain of the material (e.g., polymeric material) comprising the body of the endoprosthesis (e.g., stent) is at most about 10% in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37 °C in vitro or in vivo.
  • the plastic strain of the material (e.g., polymeric material) comprising the body of an endoprosthesis (e.g., a stent) is at least about 10%, 20%, 30%, 40%, 50% or 60% in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37 °C in vitro or in vivo.
  • aqueous condition e.g., in aqueous solution, water, saline solution or physiological conditions
  • the plastic strain of the material (e.g., polymeric material) comprising the body of the endoprosthesis (e.g., stent) is at least about 30% in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37 °C in vitro or in vivo.
  • aqueous condition e.g., in aqueous solution, water, saline solution or physiological conditions
  • the radial strength of an endoprosthesis (e.g., a stent) comprised of a biodegradable polymeric material is at least about 5, 7, 10, 12, 14, 15, 16, 18, 20, 22, 24, 25 or 30 psi in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37 °C in vitro or in vivo.
  • the radial strength of the endoprosthesis is at least about 10 or 15 psi in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37 °C in vitro or in vivo.
  • aqueous condition e.g., in aqueous solution, water, saline solution or
  • an endoprosthesis e.g., a stent
  • a biodegradable polymeric material retains at least about 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or 95% of its strength (e.g., radial strength) after a period of time (e.g., about 1, 3 or 5 days, or about 1, 2 or 3 weeks, or about 1, 2 or 3 months).
  • the endoprosthesis (e.g., stent) retains at least about 50% of its strength (e.g., radial strength) about one month after being radially expanded to an intended deployed diameter in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37 °C in vitro or in vivo.
  • aqueous condition e.g., in aqueous solution, water, saline solution or physiological conditions
  • aqueous condition e.g., in aqueous solution, water, saline solution or
  • an endoprosthesis e.g., a stent
  • a biodegradable polymeric material increases by at least about 5%, 10%, 20%, 25%, 30%, 40% or 50% in strength (e.g., radial strength) after a period of time (e.g., about 1, 2, 3, 4, 5 or 6 weeks).
  • the endoprosthesis e.g., stent
  • an endoprosthesis (e.g., a stent) comprised of a biodegradable polymeric material exhibits a percentage radially inward recoil of about 15%, 12%, 10%, 8%, 6%, 5%, 4% or 3% or less after a period of time (e.g., about 1, 3 or 5 days, or about 1, 2 or 3 weeks, or about 1, 2 or 3 months) after being radially expanded to an intended deployed diameter in aqueous condition (e.g., in aqueous solution, water, saline solution or physiological conditions) at about 37 °C in vitro or in vivo.
  • a period of time e.g., about 1, 3 or 5 days, or about 1, 2 or 3 weeks, or about 1, 2 or 3 months
  • the endoprosthesis e.g., stent
  • the stent can have any pattern and design suitable for its intended use.
  • the stent can be implanted in a subject for treatment of a wide variety of conditions, including obstruction or narrowing of a vessel (e.g., blood vessel) or other tubular tissue or organ in the body.
  • the biodegradable stent exhibits a percentage radially inward recoil of about 20% or less, or of about 15% or less, or of about 10% or less, or of about 8% or less, or of about 6% or less, upon deployment or after deployment of the stent, or at any time ranging from about day 0 to about day 30 after deployment in aqueous condition at about 37 °C in vitro or in vivo.
  • the stent exhibits percent recoil of about 10% or less after deployment, or after radial expansion in aqueous condition at about 37 °C in vitro or in vivo.
  • the biodegradable stent prosthesis comprising a tubular body comprising a biodegradable polymeric material, wherein the tubular body has been formed using extrusion, molding, dipping, or spraying, said biodegradable polymeric material has been treated to control Tg to between 35°C to 55°C, and the stent prosthesis at body temperature is radially expandable and has sufficient strength to support a body lumen and has a percent recoil lower than 15% from an expanded state.
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer or polymer is ductile and tough.
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer or polymer has high tensile strength or high elongation, or both.
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer or polymer has a tensile strength of at least about 1000 psi (about 6.9 MPa), 2000 psi (about 13.8 MPa), 3000 psi (about 20.7 MPa), 4000 psi (about 27.6 MPa), 5000 psi (about 34.5 MPa), 6000 psi (about 41.4 MPa), 7000 psi (about 48.3 MPa), 8000 psi (about 55.2 MPa), 9000 psi (about 62.1 MPa) or 10,000 psi (about 68.9 MPa).
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer or polymer has a tensile strength of at least about 3000 psi or 5000 psi. In additional embodiments, the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer or polymer has a tensile strength of about 1000 psi to about 3000 psi, or about 3000 psi to about 5000 psi, or about 5000 psi to about 10,000 psi.
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer or polymer has a weight- average molecular weight (M w ) of at least about 60,000 daltons (60 kDa), 90 kDa, 120 kDa, 150 kDa, 180 kDa, 210 kDa, or 240 kDa, or 500kDa, or 750 kDa, or lOOOkDa.
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer or polymer has an Mw of at least about 120 kDa.
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer or polymer has an M w of about 60 kDa to about 900 kDa, or about 90 kDa to about 600 kDa, or about 120 kDa to about 400 kDa, or about 150 kDa to about 250 kDa, or about 80 kDa to about 250 kDa.
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer or polymer has a M w of about 120 kDa to about 250 kDa; before treatment, or after treatment, or the stent prosthesis
  • the material e.g., polymeric material
  • the material comprising the body of the device or the biodegradable copolymer has a percent elongation at break, or at yield, or at failure of at least about 20%, 50%, 70%, 100%, 150%, 200%, 250%, 300%, 400%, 500% or 600%.
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer or polymer has a % elongation at yield or break or failure of about 20% to about 600%, or about 20% to about 300%, or about 50% to about 500%, or about 50% to about 400%, or about 50% to about 300%, or about 100% to about 400%, or about 100% to about 300%, or about 70% to about 250%, or about 100% to about 250%, or about 100% to about 200%.
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer or polymer has a % elongation at break or yield or failure of about 20% to about 300%.
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer has a tensile strength of at least about 3000 psi or 5000 psi, and a % elongation at break or failure or yield of about 20% to about 300%.
  • Ductility of a polymeric material can be increased by increasing the molecular weight and decreasing the % crystallinity of the polymeric material.
  • a polymeric material of higher molecular weight can also have increased strength (e.g., tensile strength and/or radial strength).
  • yield strength for the biodegradable polymeric stent material is at least 50% of ultimate strength, preferably at least 75% of ultimate strength, more preferably at least 90% of ultimate strength, in water at 37°C.
  • the elastic modulus for the biodegradable metallic stent material is at least 50 GPa, preferably at least 100 GPa, more preferably at least 150 GPa.
  • the elastic modulus for the biodegradable polymeric stent material is at least 0.5 GPa, preferably at least 0.75 GPa, more preferably at least 1 GPa, in water at 37 °C.
  • the yield strain for the biodegradable polymeric stent material is at most 10%, preferably at most 5%, more preferably at most 3%, in water at 37°C.
  • the plastic strain for the biodegradable polymeric stent material is at least 20%, preferably at least 30%, more preferably at least 40%, in water at 37°C.
  • the elastic recovery of the strained biodegradable polymeric stent material is at most 15%, preferably at most 10%, more preferably at most 5%, in water at 37°C.
  • the expanded biodegradable stent in physiological conditions at least after 1 month retains at least 25%, preferably at least 40%, more preferably at least 70% of the strength or recoil.
  • the strength and/or crystallinity (e.g., degree of crystallinity) of the material (e.g., polymeric material) comprising the body of an endoprosthesis (e.g., a stent) can be increased by inducing or increasing orientation of crystals, crystalline regions or polymer chains of the polymeric material substantially in the radial (circumferential) direction and/or the longitudinal direction.
  • Strength and/or crystallinity in the longitudinal direction can be increased by orienting crystals, crystalline regions or polymer chains substantially in the longitudinal direction, and strength and/or crystallinity in the circumferential direction can be increased by orienting crystals, crystalline regions or polymer chains substantially in the circumferential direction or substantially in a biaxial direction (neither preferentially circumferential nor preferentially longitudinal). Orientation of crystals, crystalline regions or polymer chains substantially in the longitudinal direction, the circumferential direction or a biaxial direction can be induced or increased by any of various methods, such as
  • Such method(s) can be performed at any suitable stage of the process for fabricating the endoprosthesis, e.g., before the polymeric article or tube is formed (e.g., heating and/or drawing of the polymeric material by extrusion), when the polymeric article or tube is being formed, after the polymeric article or tube is formed (e.g., heating, pressurizing, longitudinally extending and/or radially expanding the tube), and/or after the endoprosthesis is formed (e.g., heating, pressurizing, longitudinally extending and/or radially expanding the endoprosthesis).
  • orientation of crystals, crystalline regions or polymer chains is induced or increased substantially in a direction (e.g., longitudinal, circumferential or other direction) by expanding the polymeric article and/or the endoprosthesis in that direction while the polymeric article and/or the endoprosthesis is heated at elevated temperature, e.g., at or above the T g of the material (e.g., polymeric material) comprising the polymeric article and/or the endoprosthesis, and cooling the expanded polymeric article and/or endoprosthesis to a lower temperature (e.g., below T g ).
  • a direction e.g., longitudinal, circumferential or other direction
  • the first biodegradable polymer or material comprising the polymeric article or the body of the device is, or has crystals, crystalline regions or polymer chains that are, substantially uniaxially oriented,
  • the first biodegradable polymer or the material (e.g., polymeric material) comprising the polymeric article or the body of the device is, or has crystals, crystalline regions or polymer chains that are, substantially biaxially oriented (neither preferentially circumferentially oriented nor preferentially longitudinally oriented).
  • the first biodegradable polymer or the material (e.g., polymeric material) comprising the polymeric article or the body of the device is, or has crystals, crystalline regions or polymer chains that are, substantially not uniaxially oriented, circumferentially oriented, longitudinally oriented or biaxially oriented.
  • the first biodegradable polymer or the material (e.g., polymeric material) comprising the polymeric article or the body of the device is, or has crystals, crystalline regions or polymer chains that are, substantially randomly oriented.
  • the biodegradable polymeric stent material can have varying molecular architecture such as linear, branched, crosslinked, hyperbranched or dendritic.
  • the biodegradable polymeric stent material in the invention can range from 10 kDa to 10,000 kDa in molecular weight, preferably from 100 kDa to 1000 kDa, more preferably 300 kDa to 600 kDa.
  • a biodegradable implantable device comprising a body comprised of a material which comprises a biodegradable polylactide copolymer, wherein the material comprising the body or the polylactide copolymer is, or has crystals, crystalline regions or polymer chains that are, substantially not uniaxially oriented, circumferentially oriented, longitudinally oriented or biaxially oriented.
  • the material comprising the body of the device or the polylactide copolymer is, or has crystals, crystalline regions or polymer chains that are, substantially randomly oriented.
  • the material comprising the body of the device or the biodegradable polymer or copolymer has small-size or relatively small-size crystals or crystalline regions, or a large number or a relatively large number of small-size or relatively small-size crystals or crystalline regions. In certain embodiments, the material
  • the body of the device or the biodegradable copolymer or polymer is substantially randomly crystalline, or has substantially randomly distributed crystals or crystalline regions.
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer or polymer is, or has crystals, crystalline regions or polymer chains that are, substantially not uniaxially oriented, circumferentially oriented, longitudinally oriented or biaxially oriented.
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer is, or has crystals, crystalline regions or polymer chains that are, substantially randomly oriented.
  • the material comprising the body of the device or the biodegradable copolymer or polymer has substantially no preferred orientation or substantially no internal texture, or has crystals, crystalline regions or polymer chains that have substantially no preferred orientation or substantially no internal texture.
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer or polymer is, or has crystals, crystalline regions, molecular architecture, structural order or polymer chains that are, substantially not oriented in a particular direction, uniaxially oriented, circumferentially oriented, longitudinally oriented or biaxially oriented, in certain embodiments as a result of pressurizing or expanding in a direction a polymeric article or the device comprised of the material or the biodegradable copolymer or polymer.
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer or polymer has a number- average molecular weight (M N ) of at least about 20 kDa, 30 kDa, 40 kDa, 50 kDa, 60 kDa, 70 kDa or 80 kDa.
  • M N number- average molecular weight
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer or polymer has an M of at least about 40 kDa.
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer or polymer has an M w of at least about 60 kDa, 90 kDa, 120 kDa, 150 kDa, 180 kDa, 210 kDa or 240 kDa, and/or an M N of at least about 20 kDa, 30 kDa, 40 kDa, 50 kDa, 60 kDa, 70 kDa or 80 kDa, after the implantable device is exposed to radiation (e.g., ionizing radiation, such as e-beam or gamma radiation), or after exposure to heat and/or humidity treatment.
  • radiation e.g., ionizing radiation, such as e-beam or gamma radiation
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer or polymer has an Mw of at least about 120 kDa or an M of at least about 40 kDa, or both, after the device is exposed to radiation, or after exposure to heat/and or humidity treatment. In some embodiments, the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer or polymer has an M w of about 120 kDa to about 250 kDa after the device is exposed to radiation, or after the device is exposed to heat and/or humidity treatment.
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer or polymer has a polydispersity of about 5 or less, or about 4 or less, or about 3 or less, or about 2.5 or less, or about 2 or less, or about 1.5 or less, or about 1.
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer has a polydispersity of about 3 or less.
  • a polymeric material of substantially low polydispersity can be prepared by any of various methods, such as ionic polymerization, living polymerization, column separation, column chromatography, size separation or gel-permeation chromatography, or a combination thereof.
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer or polymer has an intrinsic viscosity of at least about O. ldl/g, or about 0.5 dl/g, or at least about 1 dl/g, or at least about 1.5 dl/g, or at least about 2 dl/g, or at least about 2.5 dl/g, or at least about 3 dl/g; optionally after the device is exposed to radiation (e.g., ionizing radiation, such as electron beam (e-beam) radiation or gamma radiation).
  • radiation e.g., ionizing radiation, such as electron beam (e-beam) radiation or gamma radiation.
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer or polymer has an inherent viscosity or an intrinsic viscosity of at least about 0.5 or at least 1 dl/g; optionally after the device is exposed to radiation.
  • the material (e.g., polymeric material) comprising the body of the device or the biodegradable copolymer or polymer has a relative viscosity of at least about 0.2 dl/g, or at least about 0.5 dl/g, or at least about 1 dl/g, optionally after the device is exposed to radiation.
  • biodegradable polymeric material comprising the body of an endoprosthesis (e.g., a stent), and the biodegradable polymeric material comprising any coating on the
  • the endoprosthesis can have any suitable molecular architecture, such as linear, branched, hyperbranched, dendritic or crosslinked.
  • the molecular weight (e.g., weight- average molecular weight or number- average molecular weight) of the polymeric material(s) can be about 10 kDa to about 10,000 kDa, or about 50 kDa to about 5000 kDa, or about 100 kDa to about 1000 kDa, or about 100 kDa to about 500 kDa, or about 100 kDa to about 300 kDa, or about 300 kDa to about 600 kDa.
  • the weight- average molecular weight of the polymeric material comprising the body of the endoprosthesis (e.g., stent), or the polymeric material comprising a coating on the endoprosthesis is about 100 kDa to about 500 kDa.
  • controlling the orientation of the polymeric material achieves the desired crystallinity, or Tg.
  • the polymeric material orientation is controlled such that the stent is capable to be crimped from an expanded condition to a crimped condition.
  • the polymeric material orientation is controlled such that the stent is capable to be expanded to a deployed diameter from a crimped configuration.
  • the polymeric material orientation is controlled such that the stent is capable to be expanded from a crimped configuration to a deployed configuration without fracture.
  • the polymeric material orientation is controlled such that the material has sufficient strength to support a body lumen.
  • the polymeric material orientation is controlled by pressurizing the polymeric material with a medium such as gas such as C0 2 wherein the orientation control affects crystallinity to a range from 1% to 35%, or 1% to 45%, or 1% to 55%.
  • Orientation of a material can be determined, measured or analyzed by any technique known in the art, including without limitation X-ray diffraction, see, e.g., D. Breiby and E. Samuelsen, J. Polymer Science Part B: Polymer Physics, 41:2375-2393 (2003), X-ray diffraction using a texture goniometer, see, e.g., O. Engler and V.
  • the polymeric article e.g., tubular body
  • the polymeric article can comprise or be comprised of a non-degradable polymeric material, a metallic material, other material described herein, or a combination thereof.
  • the polymeric article can be made by any suitable method, such as spraying, dipping, extrusion, molding, injection molding, compression molding or 3-D printing, or a combination thereof.
  • the polymeric article e.g., a polymeric tube
  • a structure e.g., a cylindrical structure such as a mandrel
  • An additional biodegradable polymer, a non- degradable polymer, a drug or an additive (e.g., a strength-enhancing material), or a combination thereof, can optionally be mixed with the polymer in the solvent so that the additional material(s) are incorporated in the polymeric article.
  • one or more coatings containing a biodegradable polymer, a non-degradable polymer, a drug or an additive, or a combination thereof can be applied to a surface of the polymeric article or to a surface of the
  • Additives can be added to the endoprosthesis to affect strength, recoil, or degradation rate, or combinations thereof. Additives can also affect processing of biodegradable stent material, radiopacity or surface roughness or others. Additives can be biodegradable or non- biodegradable.
  • the additives can be incorporated in to the biodegradable stent or polymer material by blending, extrusion, injection molding, coating, surface treatment, chemical treatment, mechanical treatment, stamping, or others or combinations thereof.
  • the additives can be chemically modified prior to incorporation in to the biodegradable stent material. In one embodiment, the percentage in weight of the additives can range from 0.01 to 25%, preferably 0.1% to 10%, more preferably 1% to 5%.
  • the additive includes at least nanoclay, nanotubes, nanoparticles, exfoliates, fibers, whiskers, platelets, nanopowders, fullerenes, nanosperes, zeolites, polymers or others or combination thereof.
  • nanoclay examples includes Montmorillonite, Smectites, Talc, or platelet- shaped particles, modified clay or others or combination thereof.
  • Clays can be intercalated or exfoliated.
  • Example of clays include Cloisite NA, 93 A, 30B, 25A,15A,10A or others or combination thereof.
  • fibers examples include cellulose fibers such as Linen, cotton, rayon, acetate;
  • proteins fibers such as wool or silk; plant fiber; glass fiber; carbon fiber; metallic fibers;
  • ceramic fibers such as polyglycolic acid, polylactic acid, polyglyconate or others.
  • whiskers examples include hydroxyapatite whiskers, tricalcium phosphate whiskers or others.
  • the additives includes at least modified starch, soybean, hyaluronic acid, hydroxyapatite, tricarbonate phosphate, anionic and cationic surfactants such as sodium docecyl sulphate, triethylene benzylammonium chloride, pro-degradant such as D2W (from Symphony Plastic Technologies) , photodegradative additives such as UV-H (from Willow Ridge Plastics), oxidative additives such as PDQ (from Willow Ridge Plastics), TDPA, family of polylactic acid and its random or block copolymers or others.
  • pro-degradant such as D2W (from Symphony Plastic Technologies)
  • photodegradative additives such as UV-H (from Willow Ridge Plastics), oxidative additives such as PDQ (from Willow Ridge Plastics), TDPA, family of polylactic acid and its random or block copolymers or others.
  • the additives include electroactive or electrolyte polymers, hydroscopic polymers, dessicants, or others.
  • the additive is an oxidizer such an acids, perchlorates, nitrates, permanganates, salts or other or combination thereof.
  • the additive is a monomer of the biodegradable polymeric stent material.
  • glycolic acid is an additive to polyglycolic acid or its copolymer stent material.
  • the additive can be water repellent monomers, oligomers or polymers such as bees wax, low MW polyethylene or others.
  • the additive can be water attractant monomers, oligomers or polymers such as polyvinyl alcohol, polyethylene oxide, glycerol, caffeine, lidocaine or other.
  • the additive can affect crystallinity of the biodegradable polymeric stent material.
  • Example of additive of nanoclay to PLLA affects its crystallinity.
  • the body of the device, or the material comprising the body of the device, or the material comprising one or more layers of the body of the device comprises one or more additives.
  • the additive(s) can serve any of a variety of functions, including without limitation facilitating processing of the material comprising the body (or the material comprising any coating on the body), imparting surface roughness to a surface of a polymer layer in the body or on the body (e.g., to improve adhesion of a metal layer to the polymer layer in the body or on the body of the device), imparting radiopacity to the device, and controlling physical characteristics of the material comprising the body (or the material comprising any coating on the body), such as controlling (e.g., promoting or slowing down) its degradation and/or controlling its crystallinity, enhancing its strength, and enhancing its toughness.
  • the additive(s) can be biodegradable or non-degradable.
  • the additive(s) can be incorporated in and/or on the body (and in and/or on any coating on the body of the device) by any suitable method, such as mixing, blending, spraying, dipping, extrusion, injection molding, coating, printing, surface treatment, chemical treatment, mechanical treatment, stamping, or a combination thereof.
  • the weight percent of an additive in the material (e.g., polymeric material) comprising the body of the device, or the material (e.g., polymeric material) comprising a particular layer in the body, or the material (e.g., polymeric material) comprising a particular coating on the body is about 0.01 or 0.1% to about 50%, or about 0.01% or 0.1% to about 40%, or about 0.01% or 0.1% to about 30%, or about 0.01% or 0.1% to about 25%, or about 0.05% or 0.1% to about 20%, or about 0.05% or 0.1% to about 15%, or about 0.1% to about 10% or 20%, or about 0.5% to about 10% or 20%, or about 1% to about 10% or 20%, or about 0.5% or 1% to about 5%.
  • the weight percent of an additive in the material (e.g., polymeric material) comprising the body of the device, or the material (e.g., polymeric material) comprising a particular layer in the body, or the material (e.g., polymeric material) comprising a particular coating on the body is about 0.1% to about 25%.
  • Non-limiting examples of additives include nanotubes, carbon nanotubes, carbon nano fibers, boron nanotubes, fullerenes, nanoparticles, nanospheres, nanopowders, nanoclays, zeolites, exfoliates, fibers, whiskers, platelets, polymers, monomers, oxidizers, stabilizers, antioxidants, butylated hydroxytoluene (BHT), degradation-controlling agents, buffers, conjugate bases, weak bases, getters, ionic surfactants, salts, barium salts, barium sulfate, calcium salts, calcium carbonate, calcium chloride, calcium hydroxyapatite, tricalcium phosphate, magnesium salts, sodium salts, sodium chloride, blowing agents, gases, carbon dioxide, solvents, methanol, ethanol, isopropanol, dichloromethane,
  • dimethylsulfoxide metals, metal alloys, semi-metals, ceramics, radiopaque agents, and contrast agents.
  • nanoclays examples include, but are not limited to, montmorillonites, smectites, bentonites, talc, particles have any desired shape (e.g., platelet-shaped particles), and modified clays. Additional examples of nanoclays include Cloisite® NA, 10A, 15 A, 25 A, 30B and 93A. Nanoclays can be, e.g., intercalated or exfoliated, and can serve any of a variety of functions, such as controlling crystallinity of the material (e.g., polymeric material) comprising the body of the device or a coating on the body, e.g., a nanoclay as an additive can affect crystallinity of poly(L-lactide).
  • the material e.g., polymeric material
  • a nanoclay as an additive can affect crystallinity of poly(L-lactide).
  • fibers include without limitation plant fibers and cellulose fibers (e.g., linen, cotton, rayon and cellulose acetate), proteins fibers (e.g., wool and silk), glass fibers, carbon fibers, metallic fibers, ceramic fibers, and absorbable polymeric fibers (e.g., polyglycolic acid/polyglycolide, polylactic acid/polylactide, poly(lactide-co-E-caprolactone), and polyglyconate).
  • whiskers include, but are not limited to, hydroxyapatite whiskers and tricalcium phosphate whiskers.
  • the additives can be a blowing agent, which is a substance capable of producing a cellular structure in a variety of materials that undergo hardening or phase transition, such as polymers, plastics and metals.
  • the blowing agent can be applied when the material is in a liquid stage or in a liquid solution or mixture.
  • Blowing agents include without limitation gases (e.g., compressed gases) that expand when pressure is released, solids (e.g., soluble solids) that form pores when they leach out from the material, liquids that develop a cellular structure (e.g., cells) when they change to gases, and chemical agents that decompose or react under the influence of heat or radiation to form, e.g., a gas or a solid that can form pores when it leaches out.
  • Chemical blowing agents include, but are not limited to, salts (e.g., ammonium and sodium salts, such as ammonium and sodium bicarbonate) and nitrogen- releasing agents.
  • radiopaque agents and material that can be additives include without limitation barium sulfate, gold, magnesium, platinum, platinum-iridium alloys (e.g., those containing at least about 1%, 5%, 10%, 20% or 30% iridium), tantalum, tungsten, and alloys thereof.
  • the radiopaque agent or material can be in any suitable form (e.g., nanoparticle or microparticle), and in amounts ranging from about 0.1% to about 10%.
  • Contrast agents include without limitation radiocontrast agents and MRI contrast agents.
  • radiocontrast agents include iodine-based agents, ionic iodine-based agents, diatrizoate, ioxaglate, metrizoate, non-ionic (organic) iodine-based agents, iodixanol, iohexol, iopamidol, iopromide, ioversol, ioxilan, barium-based agents, and barium sulfate.
  • Non-limiting examples of MRI contrast agents include gadolinium-based agents, gadobenic acid, gadobutrol, gadocoletic acid, gadodenterate, gadodiamide, gadofosveset, gadomelitol, gadopenamide, gadopentetic acid, gadoteric acid, gadoteridol, gadoversetamide, gadoxetic acid, iron oxide-based agents, Cliavist, Combidex®, Endorem (Feridex), Resovist®, Sinerem, manganese-based agents, and mangafodipir (Mn(II)- dipyridoxyl diphosphate).
  • gadolinium-based agents gadobenic acid, gadobutrol, gadocoletic acid, gadodenterate, gadodiamide, gadofosveset, gadomelitol, gadopenamide, gadopentetic acid, gadoteric acid, gadoterid
  • the additives can also be selected from modified starch, soybean, hyaluronic acid, hydroxyapatite, tricarbonate phosphate, Totally Degradable Plastic Additive (TDPATM), desiccants (e.g., calcium sulfate, calcium chloride, activated alumina, silica gel,
  • TDPATM Totally Degradable Plastic Additive
  • desiccants e.g., calcium sulfate, calcium chloride, activated alumina, silica gel,
  • montmorillonites, zeolites and molecular sieves e.g., anionic and cationic surfactants (e.g., sodium dodecyl sulphate and triethylene benzylammonium chloride), pro-degradant additives (e.g., D2W from Symphony Plastic Technologies), photodegradative additives (e.g., UV-H from Willow Ridge Plastics), oxidative additives (e.g., PDQ from Willow Ridge Plastics), and oxidizers (e.g., acids, salts, perchlorates, nitrates and permanganates).
  • anionic and cationic surfactants e.g., sodium dodecyl sulphate and triethylene benzylammonium chloride
  • pro-degradant additives e.g., D2W from Symphony Plastic Technologies
  • photodegradative additives e.g., UV-H from Willow Ridge Plastics
  • oxidative additives e.g., PDQ from
  • the additives can be selected from electroactive polymers, electrolyte polymers, hygroscopic polymers, and hydrophilic polymers (e.g., polylactic acid/polylactide and polyglycolic acid/polyglycolide and copolymers thereof).
  • the additives can also be monomers of the polymeric material comprising the body of the device (or the polymeric material comprising a coating on the body).
  • glycolic acid or glycolide is an additive for a polymer containing glycolic acid/glycolide, e.g., polyglycolic
  • acid/polyglycolide or a copolymer thereof, such as poly(lactide-co-glycolide), lactic acid or lactide is an additive for a polymer containing lactic acid/lactide, e.g., polylactic
  • acid/polylactide or a copolymer thereof, such as poly(lactide-co-glycolide), and ⁇ - caprolactone is an additive for a polymer containing ⁇ -caprolactone, e.g., poly(£- caprolactone) or a copolymer thereof, such as poly(lactide-co-E-caprolactone).
  • Additives that are monomers can serve any of a variety of functions, such as controlling degradation of the material (e.g., polymeric material) comprising the body of the device or a coating on the body (e.g., acidic monomers such as glycolic acid and lactic acid can promote degradation of the polymeric material), or plasticizing or softening the polymeric material, which can, e.g., reduce its crystallinity or brittleness and enhance its toughness.
  • monomers of a different type than copolymers or polymers can be used.
  • the additives are degradation-controlling agents that control degradation of the material (e.g., polymeric material) comprising the body of the device or a coating on the body, or that control degradation of any portion of the device.
  • degradation-controlling agents include salts (e.g., aluminum chloride, calcium chloride, ferric chloride, magnesium chloride, sodium chloride and zinc chloride), acids (e.g., ammonium chloride, aminosulfonic acid, hydrochloric acid, hydrofluoric acid, nitric acid, phosphoric acid, sulfuric acid, hexafluorosilicic acid, sodium bisulfite, acetic acid, adipic acid, hydroxyadipic acids, citric acid, formic acid, lactic acid and oxalic acid), bases (e.g., potassium hydroxide, sodium hydroxide, calcium carbonate, potassium carbonate, sodium carbonate, potassium bicarbonate, sodium bicarbonate, phosphates, potassium phosphate, sodium phosphate,
  • the additives are degradation-controlling agents that promote degradation of a non-degradable polymer.
  • pro-degradant additives such as D2W
  • photodegradative additives such as UV-H
  • oxidative additives such as PDQ
  • TDPATM Totally Degradable Plastic Additive
  • non-degradable polymers such as polyethylene, polypropylene and poly(ethylene terephthalate).
  • the additives are degradation-controlling agents that help to resist degradation of a material (e.g., a polymer, a metal or metal alloy, a biologically active agent, or another additive), such as oxidative degradation, photodegradation, high energy- exposure degradation, thermal degradation, hydrolytic degradation, acid-catalyzed degradation, or other kinds of degradation.
  • a material e.g., a polymer, a metal or metal alloy, a biologically active agent, or another additive
  • oxidative degradation e.g., photodegradation, high energy- exposure degradation, thermal degradation, hydrolytic degradation, acid-catalyzed degradation, or other kinds of degradation.
  • Non-limiting examples of additives that can help to resist degradation of a material include antioxidants, e.g., vitamin C and butylated hydroxy toluene (BHT), stabilizers (e.g., xanthum gum, succinoglycan, carrageenan and propylene glycol alginate), getters (e.g., titanium-containing beads and aluminium oxide), salts (e.g., calcium chloride), and bases (e.g., potassium carbonate, sodium carbonate, potassium bicarbonate, sodium bicarbonate, sodium sulfate and magnesium sulfate).
  • antioxidants e.g., vitamin C and butylated hydroxy toluene (BHT)
  • stabilizers e.g., xanthum gum, succinoglycan, carrageenan and propylene glycol alginate
  • getters e.g., titanium-containing beads and aluminium oxide
  • salts e.g., calcium chloride
  • bases e.g., potassium
  • the additives can be water-attractant substances such as glycerol, caffeine, lidocaine, monomers, oligomers or polymers (e.g., polyvinyl alcohol or polyethylene oxide).
  • the additives can also be water-repellent substances such as monomers, oligomers, polymers (e.g., low molecular weight polyethylene) or waxy substances (e.g., beeswax).
  • Water- attractant additives can serve any of a variety of functions, including promoting degradation of the material (e.g., polymeric material) comprising the body of the device or a coating on the body and permeation of water into the polymeric material, which can swell the polymeric material, reduce its brittleness and increase its toughness.
  • Water-repellent additives can serve any of a variety of functions, including slowing down degradation of the material (e.g., polymeric material) comprising the body of the device or a coating on the body.
  • the additives are additives that reduce water absorption, act as a water barrier or react with water (designed, e.g., to control degradation of the device, control elasticity or ductility of a polymeric material comprising the device, or control self- expansion of a self-expandable device in aqueous condition at about 37 °C).
  • the additives can be metals or metal alloys that react with water, such as magnesium, magnesium alloys, iron or iron alloys.
  • the additives can be salts that react with water, such as calcium salts, magnesium salts or sodium salts.
  • Additives that might be non-degradable can be removed by a variety of means, such as by cells (e.g., macrophages and monocytes) or by excretion (e.g., when they are not used in a large amount).
  • cells e.g., macrophages and monocytes
  • excretion e.g., when they are not used in a large amount
  • the material (e.g., polymeric material) comprising the body of the device, or the material (e.g., polymeric material) comprising a particular layer of the body comprises novolimus and an antioxidant.
  • the antioxidant is butylated hydroxytoluene (BHT).
  • BHT butylated hydroxytoluene
  • the weight percent of the antioxidant in the novolimus-containing material is about 0.1% to about 2%, or about 0.1% to about 1%, or about 0.5% to about 1%.
  • the material (e.g., polymeric material) comprising the body of the device or any particular layer or all layers of the body comprises novolimus and BHT, wherein the weight percent of the BHT in the material is about 0.1% to about 1%.
  • the biodegradable implantable devices described herein comprise one or more reinforcement additives.
  • the reinforcement additives can improve properties of the devices, such as strength (e.g., tensile strength, radial strength) and modulus (e.g., elastic modulus, tensile modulus). Further, the additives can increase retention or control release of a biologically active agent, e.g., as a result of physical interaction, non- covalent interaction (e.g., van der Waals interaction or hydrogen bonding), and/or covalent interaction (e.g., if the additives are functionalized) between the additive and the bioactive agent.
  • strength e.g., tensile strength, radial strength
  • modulus e.g., elastic modulus, tensile modulus
  • the additives can increase retention or control release of a biologically active agent, e.g., as a result of physical interaction, non- covalent interaction (e.g., van der Waals interaction or hydrogen bonding), and/or covalent
  • Non-limiting examples of reinforcement additives include nanotubes (including carbon nanotubes/nanofibers and boron nanotubes/nanofibers), fullerenes (including buckyballs), nanoparticles, nanospheres, nanopowders, nanoclays, zeolites, exfoliates, fibers (including nanofibers), whiskers, platelets and polymers. Nanoclays can be added to one or more polymers comprising the body of the device or a coating on the device by any suitable method, such as in situ polymerization intercalation, melt intercalation and solution intercalation.
  • the reinforcement additives incorporated in the body of the device, a layer of the body or a coating on the device include carbon nanotubes.
  • the device comprising one or more reinforcement additives is a stent.
  • the weight percent of a reinforcement additive in the material (e.g., polymeric material) comprising the body of the device, or the material (e.g., polymeric material) comprising a layer of the body, or the material (e.g., polymeric material) comprising a coating on the device is about 0.01% or 0.1% to about 25%, or about 0.1% to about 15% or 20%, or about 0.1% or 0.25% to about 10%, or about 0.25% or 0.5% to about 5%, or about 1% to about 5%. In certain embodiments, the weight percent of a reinforcement additive is about 0.5% to about 5%, or about 1% to about 3%.
  • the volume fraction or volume percent of a reinforcement additive in the body of the device, a layer of the body or a coating on the device is about 0.05% or 0.1% to about 25%, or about 0.25% or 0.5% to about 10%, or about 0.75% or 1% to about 5%. In certain embodiments, the volume fraction or volume percent of a reinforcement additive is about 0.75% to about 5%, or about 1% to about 3%.
  • the material (e.g., polymeric material) comprising the body of the device, or the material (e.g., polymeric material) comprising a particular layer of the body comprises nanotubes (e.g., carbon nanotubes, boron nanotubes) or one or more other reinforcement additives having a larger feature (e.g., length) and a smaller feature (e.g., diameter or width) such that the ratio of these two features results in a relatively high aspect ratio.
  • the average aspect ratio (e.g., length divided by diameter or width) of a reinforcement additive is about 2 to about 40,000, or about 10 or 30 to about 25,000, or about 100 to about 1000, 5000 or 10,000, or about 50 or 100 to about 500.
  • incorporación of one or more reinforcement additives having a relatively high aspect ratio in the material comprising the body of the device or a layer of the body can improve properties of the device.
  • use of such reinforcement additives can increase the strength (e.g., tensile strength, radial strength), stiffness, modulus (e.g., tensile modulus, elastic modulus), toughness, crack resistance, fatigue resistance, work to failure, and/or thermal conductivity of the device (e.g., a stent), and can decrease cracking, fatigue, creep and/or recoil of the device.
  • the material (e.g., polymeric material) comprising the body of the device, or the material (e.g., polymeric material) comprising a particular layer of the body comprises carbon nanotubes.
  • Carbon nanotubes can be strong and flexible, and can enhance properties of the material, such as increasing its strength (e.g., tensile strength, radial strength) and/or modulus (e.g., elastic modulus, tensile modulus) without substantially decreasing its ductility.
  • the device comprising carbon nanotubes is a stent.
  • the carbon nanotubes can be single-walled carbon nanotubes (SWCNTs), double-walled carbon nanotubes (DWCNTs), and/or multi-walled carbon nanotubes
  • MWCNTs In certain embodiments, the number of walls of MWCNTs is about 2 to about 5, 10, 15 or 20. In an embodiment, the number of walls of MWCNTs is about 2 to about 4. MWCNTs can potentially be straighter and/or more crystalline than SWCNTs, and can potentially provide higher mechanical properties than SWCNTs. SWCNTs can comprise a graphene sheet rolled into a cylinder, and MWCNTs can comprise multiple concentric graphene cylinders. Carbon nanotubes can be produced by any suitable method, such as high-temperature evaporation using arc discharge, laser ablation, chemical vapor deposition, high-pressure carbon monoxide, or a catalytic growth process.
  • the average length of the carbon nanotubes is about 100 nm to about 50 or 100 mm, or about 500 nm to about 0.5 or 1 mm, or about 500 nm to about 50 or 100 ⁇ , or about 1 or 5 ⁇ to about 50 ⁇ , or about 10 ⁇ to about 20 ⁇ .
  • the average diameter of the carbon nanotubes is about 0.4 nm to about 1 ⁇ , or about 1 nm to about 100 or 500 nm, or about 10 or 30 nm to about 50 nm.
  • the average aspect ratio (length divided by diameter) of the carbon nanotubes is about 2 to about 40,000, or about 10 or 30 to about 25,000, or about 100 to about 1000, 5000 or 10,000.
  • the average surface area of the carbon nanotubes is about 10 to about 1000 m 2 /g, or about 25 to about 750 m 2 /g, or about 50 or 100 to about 500 m 2 /g.
  • the purity of the carbon nanotubes is at least about 50%, 60%, 70%, 75%, 80%, 90%, 95%, 96%, 97%, 98% or 99%. In an embodiment, the purity of the carbon nanotubes is at least about 95%.
  • impurities of carbon nanotubes include amorphous carbon, heavy metals and/or chemicals.
  • the material (e.g., polymeric material) comprising the body of the device or a particular layer of the body comprises carbon nanotubes in a weight percent of about 0.1% or 0.5% to about 10%, or about 0.1% or 0.5% to about 5%, or about 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9% or 10%.
  • the material (e.g., polymeric material) comprising the body of the device or a particular layer of the body comprises carbon nanotubes in a weight percent of about 0.1% or 0.5% to about 3%, or about 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5% or 3%.
  • the carbon nanotube-containing material comprises a polylactide
  • the material comprising the body of the device or a particular layer of the body comprises a poly(L-lactide) copolymer, e.g., poly(L-lactide-co-E-caprolactone) or any other poly(L-lactide) copolymer described herein, and carbon nanotubes in a weight percent of about 0.1% or 0.5% to about 3%, or about 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5% or 3% (e.g., about 2%).
  • One or more reinforcement additives can be incorporated in the body of the device or a coating on the device in any of a variety of ways.
  • one or more additives are mixed or dispersed in one or more polymers comprising the body of the device, a layer of the body or a coating on the device when the polymer(s) are untangled or lack form or crystalline structure, which can promote interaction or incorporation of the additive(s) with the polymer molecules.
  • Substantially amorphous polymers or semi crystalline polymers or polymers of lower crystallinity can have higher loading of additives, which can result in greater increase in strength and/or toughness and/or lower creep.

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Abstract

Selon l'invention, des endoprothèses biodégradables sont fabriquées sous la forme d'un corps tubulaire comprenant un matériau polymère biodégradable. Ces endoprothèses sont extensibles, pouvant passer d'une configuration sertie à une configuration étendue, et présentent une résistance radiale et une conformabilité.
PCT/US2015/012780 2014-01-24 2015-01-23 Endoprothèses biodégradables et leurs procédés de fabrication WO2015112915A1 (fr)

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