WO2021247024A1 - Échafaudage métallique biodégradable radio-opaque ayant un revêtement non biodégradable, et qui comprend des bagues de support radiales et des liaisons axiales souples de manière résiliente, de préférence fracturables entre ces dernières - Google Patents

Échafaudage métallique biodégradable radio-opaque ayant un revêtement non biodégradable, et qui comprend des bagues de support radiales et des liaisons axiales souples de manière résiliente, de préférence fracturables entre ces dernières Download PDF

Info

Publication number
WO2021247024A1
WO2021247024A1 PCT/US2020/036045 US2020036045W WO2021247024A1 WO 2021247024 A1 WO2021247024 A1 WO 2021247024A1 US 2020036045 W US2020036045 W US 2020036045W WO 2021247024 A1 WO2021247024 A1 WO 2021247024A1
Authority
WO
WIPO (PCT)
Prior art keywords
scaffold
coating
preferentially
fracturable
radial support
Prior art date
Application number
PCT/US2020/036045
Other languages
English (en)
Inventor
John Shulze
Jianfong Tan
Original Assignee
Biovascular Therapeutics Pte Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Biovascular Therapeutics Pte Ltd filed Critical Biovascular Therapeutics Pte Ltd
Publication of WO2021247024A1 publication Critical patent/WO2021247024A1/fr

Links

Classifications

    • 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
    • A61L31/02—Inorganic materials
    • A61L31/022—Metals or alloys
    • 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
    • A61L31/08—Materials for coatings
    • A61L31/10—Macromolecular materials
    • 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
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • 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
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/148—Materials at least partially resorbable by the body
    • 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
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/18—Materials at least partially X-ray or laser opaque
    • 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
    • A61F2210/0076—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof multilayered, e.g. laminated structures
    • 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
    • A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2250/0014—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis
    • A61F2250/003—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis differing in adsorbability or resorbability, i.e. in adsorption or resorption time
    • A61F2250/0031—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis differing in adsorbability or resorbability, i.e. in adsorption or resorption time made from both resorbable and non-resorbable prosthetic parts, e.g. adjacent parts
    • 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
    • A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2250/0058—Additional features; Implant or prostheses properties not otherwise provided for
    • A61F2250/0067—Means for introducing or releasing pharmaceutical products into the body
    • 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
    • A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2250/0058—Additional features; Implant or prostheses properties not otherwise provided for
    • A61F2250/0096—Markers and sensors for detecting a position or changes of a position of an implant, e.g. RF sensors, ultrasound markers
    • A61F2250/0098—Markers and sensors for detecting a position or changes of a position of an implant, e.g. RF sensors, ultrasound markers radio-opaque, e.g. radio-opaque markers
    • 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
    • A61L2420/00—Materials or methods for coatings medical devices
    • A61L2420/08—Coatings comprising two or more layers

Definitions

  • the present disclosure relates to a scaffold structure implantable in an anatomical lumen of a living human or animal body. More particularly, the present disclosure is directed to an implantable scaffold structure including a biodegradable metallic scaffold that carries a non- biodegradable material, layer, or coating that insulates, separates, or isolates the metallic scaffold from a radiopaque material, layer, or coating.
  • the scaffold structure is formed to include multiple radial support segments, sections, or rings, between which resiliently flexible and preferentially fracturable axial coupling / decoupling members or links are disposed.
  • scaffold structures e.g., vascular stents
  • vascular stents vascular stents
  • scaffold structures can broadly be categorized as (a) non-resorbable scaffolds, which retain their compositional integrity throughout the time they reside within the anatomical lumen in which they are implanted; or (b) bioresorbable scaffolds, which gradually deteriorate or break down over time as a result of exposure to the environment in the lumen.
  • bioresorbable scaffolds substantially all of the material(s) incorporated into the scaffold can be biodegraded into materials that can be resorbed (i.e., metabolized and/or excreted by a living body).
  • vascular scaffolds one of the most important asserted benefits is "vessel restoration", i.e., the gradual degradation of mechanical strength of the scaffold, thus freeing the vessel from the scaffold's underlying frame or cage structure, to enhance the flexibility and health of the vessel after angioplasty.
  • a scaffold that is formed of a radiolucent material is transformed into a radiopaque scaffold by carrying one or more radiopaque materials, such as by way of a radiopaque coating or layer applied to the scaffold's cage.
  • the protective layer further includes thereupon a second "biocompatible and blood compatible" material which is a polymer, a metal, or a ceramic".
  • a second "biocompatible and blood compatible” material which is a polymer, a metal, or a ceramic.
  • An adhesion layer is used to prevent "stretching and straining" of the protective layer during flexing of the stent.
  • the previously described protective layer is first applied to cover the stent and the radiopaque layer is applied to partially or completely cover the protective layer.
  • the radiopaque layer is said to be "scratch resistant and biocompatible”.
  • FIG. 1 shows portions of a stent constructed as described in U.S. Patent 6,174,329.
  • an outermost radiopaque coating even when applied in a very thin layer, tends to be very fragile and brittle, as indicated in FIG. 1. It can be seen from FIG. 1 that there is a problem with excessive flaking of an unprotected radiopaque coating during delivery and expansion of the stent when the radiopaque coating comprises the outermost coating layer of the stent.
  • bioresorbable scaffolds With respect to bioresorbable scaffolds, most biodegradable materials that have useful properties after implantation in an internal lumen (e.g., biocompatibility, maintenance of adequate mechanical strength over a required healing period, favorable processing properties, etc%) have inadequate radiopacity, particularly for the construction of vascular stents having a typical wall thickness in the range of 60-180 micrometers. This has led the development of bioresorbable scaffolds having radiopaque coatings applied thereto.
  • U.S. Patent 7,951,194 describes a bioresorbable polymer scaffold with a radiopaque coating containing radiopaque particles dispersed in a biodegradable coating, and a topcoat layer of biodegradable polymer.
  • U.S. Patent 9,265,866 describes a bioresorbable scaffold with a polymer coating that contains radiopaque particles. The particles are made from two dissimilar metals, which leads to galvanic corrosion of the particles.
  • FIG. 2 is an angiographic image of a Mg scaffold having a radiopaque material directly in contact with the Mg, and which further includes an outer protective layer, at an in vivo post-implantation time of 4 weeks.
  • a large amount of restenosis has occurred in the region in which the scaffold was implanted, despite the outer protective layer.
  • a key property that must be considered in the design of bioresorbable scaffolds is the scaffold degradation or resorption rate, particularly with respect to (i) a target or desired length of time that the scaffold should continue to provide sufficient structural integrity in order for vessel healing to occur, and (ii) the extent to which the products of premature scaffold degradation can adversely affect vessel healing.
  • U.S. Patent Publication 20100076544 describes a bioresorbable metal scaffold surrounded by a polymeric coating that has a slower degradation rate than the underlying metal scaffold.
  • U.S. Patent 9,474,637 describes a high molecular weight, acid-generating polymer coating which is said to reduce the degradation rate of a bioresorbable polymeric scaffold.
  • the coating may also contain a therapeutic substance.
  • the AMS-3 bioresorbable Mg scaffold as manufactured by the Biotronik company (Int. J. Mol. Sci. 2011, 4258) and described in U.S. Patent Publication 20090240323, uses a fast degrading polymer coating to reduce the degradation rate of its Mg body or core structure.
  • the polymer coating may contain a therapeutic substance to reduce restenosis or thrombosis during the healing phase.
  • Lu et al. Colds Surf. B Biointerfaces 2010, 83, 23-28 reported the fabrication of bioresorbable AZ81 Mg alloy stent coated with a composite multi-layer biodegradable film for controlling the biodegradation rate of the Mg alloy.
  • the teachings of the bioresorbable scaffold art are overwhelmingly directed toward applying biodegradable coatings to reduce the degradation rate of the base or core scaffold material.
  • devices manufactured with biodegradable anti-corrosion coatings as described in the prior art do not adequately slow the scaffold degradation rate, as the described coatings do not maintain adequate physical and chemical isolation of the base material of the scaffold body from fluid entry.
  • localized rapid corrosion of the base scaffold material can occur, which results in undesirably early scaffold failure, and accompanying increases in tissue inflammation and restenosis.
  • FIG. 3 shows an idealized degradation time and radial strength curves for a commercially available Mg bioresorbable scaffold or stent.
  • scaffolding decreases significantly around 3 months, which is still too fast because it occurs before sufficient tissue healing has occurred.
  • the degradation products from the implanted scaffold structure significantly affect the healing of the vessel while the vessel is still in a fragile state.
  • this bioresorbable stent is already well along in its degradation process while the vessel is still healing, which may take typically 9 - 12 months in a diseased blood-carrying vessel of the human anatomy.
  • the outer biodegradable coating can be easily damaged during handling, stent insertion, and expansion, resulting in early coating failure, much faster degradation, structural failure, excessive release of degradation products, inflammation, and restenosis.
  • FIG. 4A shows an intraluminal optical coherence tomography (OCT) image of a newly implanted commercially available Mg bioresorbable scaffold in a human coronary artery.
  • OCT optical coherence tomography
  • FIG. 4B shows an early failure of the same implant at 4 months due to biodegradable coating failure and undesirably rapid degradation, leading to breakup of the stent struts, and resulting in severe restenosis and vessel failure.
  • FIG. 5 is a collection of OCT showing time progress of strut degradation in a bioresorbable stent with a prior art biodegradable coating, where there is heterogeneous progression of strut degradation, undesirably resulting in variable radial support by different portions of the stent over time.
  • U.S. Patent Publication 20090208555 describes a biodegradable coating for bioresorbable implants, where the coating is biodegradable polymer which may be selectively applied to slow down the degradation rate of only certain portions of the implant.
  • U.S. Patent Publication 201100076319 describes a bioresorbable Mg scaffold with a biodegradable, fluid permeable polymer wrap. The scaffold has interconnecting elements which are have smaller cross section than the radial support elements, which is asserted to allow for faster degradation of the interconnecting elements that provide axial strength.
  • Patent 8,425,587 describes a bioresorbable stent containing straight links between axially spaced radial support bands. Some of the straight links are modified to contain failure points adapted to break before the radial support bands. However, due to the presence of the interconnecting straight links between the rings, the unexpanded stent has poor axial flexibility prior to link failure, including during delivery and deployment.
  • U.S. Patent 7,811,622 describes a bioresorbable polymer scaffold structure in which a non- porous coating is applied over the scaffold, where the non-porous coating can be non- degradable; a bioactive layer is applied over the non-porous coating specifically for carrying a bioactive material; and a porous coating is applied over the bioactive layer for controlling the release of the bioactive material.
  • the bioactive layer can include a radiopaque agent therein.
  • a porous coating that allows radiopaque particles such as tantalum (Ta) particles to leach out of the bioactive layer may lead to unpredictable or undesirable tissue response. For instance, as shown by W. Van Oeveren et al. (Prog, in Biomed. Res.
  • aspects of the present disclosure are directed to scaffold (e.g., stent) structures or devices that are introducible or implantable into a lumen of an anatomical passage, channel, conduit, vessel, or duct of a living body, and which overcome at least some of the aforementioned shortcomings of the prior art.
  • scaffold e.g., stent
  • an implantable scaffold structure in accordance with multiple embodiments of the present disclosure includes bioresorbable or biodegradable materials, but is not entirely composed of bioresorbable or biodegradable materials.
  • an implantable scaffold or stent structure in accordance with an embodiment of the present disclosure includes some biodegradable materials, or mostly biodegradable materials (e.g., in some embodiments, the thickness of non-biodegradable materials is 20 micrometers / microns or less, such as 10 micrometers or less (e.g., between approximately 0.1 - 10 micrometers, 0.1 - 7.5 micrometers, 0.1 - 5 micrometers, 0.1 - 4 micrometers, 0.1 - 3 micrometers, 0.1 - 2.5 micrometers, 0.1 - 2 micrometers, 0.5 - 4 micrometers, 0.5 - 3 micrometers, 0.5 - 2.5 micrometers, 0.5 - 2 micrometers, 1 - 4 micrometers, 1 - 3 micrometers, or 1 - 2 micrometers) on each of an inner or inward facing surface and outer or outward facing surface of an underlying biodegradable metallic scaffold).
  • the thickness of non-biodegradable materials is 20 micrometers
  • Such embodiments can actually achieve the intended objective of "vessel restoration” and provide essentially the same type of functionality as a fully bioresorbable scaffold, but with significantly or greatly improved degradation time profiles relative to a time period desired or required for significant tissue healing to occur. Moreover, such embodiments provide the added benefit of substantially lower or reduced release of inflammatory degradation products because some of the materials of the scaffold structure are non-degradable.
  • An implantable, ready for implantation, or implanted scaffold or stent structure in accordance with various embodiments of the present disclosure includes: (a) a biodegradable metallic scaffold or stent formed from a magnesium (Mg) alloy, which provides an underlying or base material composition or material that establishes a scaffold or stent body corresponding to or defining a frame or cage structure; (b) a first material composition or material, coating, or layer (e.g., in the form of one or more polymers) carried by the scaffold or stent body that substantially reduces the in vivo degradation rate of the base material, and which is a durable, i.e., non-degradable, conformal material composition or material, coating, or layer relative to the scaffold or stent body; and (c) one or more additional material compositions, coatings, or layers to increase the radiopacity of the stent, while also (i) preventing flaking of radiopaque material(s) from the scaffold or stent structure, and/or (ii)
  • a biodegradable metallic scaffold or stent structure in accordance with embodiments of the present disclosure includes a biodegradable metallic stent body carrying a coating (e.g., a non-biodegradable polymer coating) that substantially reduces and predictably and/or uniformly controls the degradation rate of the underlying scaffold or stent body throughout various or different sections of the biodegradable metallic scaffold or stent body.
  • a biodegradable metallic scaffold or stent structure in accordance with embodiments of the present disclosure provides a sufficiently long degradation time (or a sufficiently slow degradation rate) to allow an anatomical lumen or vessel into which the scaffold or stent structure has been introduced or implanted to substantially heal prior to any significant loss of scaffold or stent radial strength or significant release of degradation products.
  • a biodegradable metallic scaffold or stent structure in accordance with embodiments of the present disclosure is visible under X-ray fluoroscopy by way of additionally carrying a radiopaque material, coating, or layer, wherein the radiopaque layer is protected from flaking and mechanical abrasion during stent insertion, delivery, and expansion.
  • a biodegradable metallic scaffold or stent structure is compressible and expandable, and includes multiple radial support structures that are initially coupled or joined together by way of non-linear, curved, curvilinear, or bent axial coupling members or links that are at least slightly resilient with respect to axial displacement of the radial support structures.
  • Such a biodegradable metallic scaffold or stent structure exhibits increased or increasing post-implant axial flexibility by way of increased or increasing decoupling of radial support structures from each other, such as by way of preferential breakage or rupture of the axial coupling members in response to forces (e.g., repeated compressive forces) imparted thereto after implantation.
  • the materials, coatings, or layers carried by the metallic scaffold or stent are stretchably, flexibly, and/or slidably carried by, overlaid upon, or attached to the metallic scaffold or stent body, and are sufficiently stretchable and malleable to allow for the decoupling of the radial support structures without compromising the intended functions of slowing degradation time, providing increased radiopacity, preventing flaking, and/or releasing a therapeutic agent.
  • a biodegradable metallic stent structure in accordance with an embodiment of the present disclosure is sufficiently flexible in its unexpanded state when attached to an angioplasty balloon to be easily delivered to an atherosclerotic lesion through tortuous vessel anatomy.
  • fewer than approximately 10%, or less than about 5%, of the aforementioned axial coupling members rupture or are broken in response to compressive forces experienced thereby during stent structure implantation.
  • a scaffold structure which is implantable into an anatomical lumen of a human or animal body.
  • the scaffold structure is an elongate structure having a length.
  • a central axis is definable through or internal to the elongate scaffold structure along its length.
  • the scaffold structure as- manufactured includes, is formed as, or consists essentially of, or consists of: an elongate biodegradable metallic scaffold that provides a frame or cage structure; a non-porous inner coating disposed over the biodegradable metallic scaffold, wherein the inner coating includes a non-biodegradable polymer that conformally encases the scaffold, such that an inner surface of the inner coating is disposed adjacent to and in contact with the scaffold; a non-porous outer coating comprising a biodegradable or non-biodegradable polymer, the outer coating having an outer or outermost surface (e.g., an exposed outer surface); and a radiopaque material disposed external to the inner coating and internal to the outer or outermost surface (e.g., the exposed outer surface) of the outer coating along the scaffold structure's length, wherein the inner coating electrochemically isolates the radiopaque material from the scaffold.
  • the inner coating can include or be a resilient, pinhole free parylene sheath that conformally coats the scaffold and which exists in slidable and/or flexible contact with the scaffold.
  • the radiopaque material can include or be a coating of Tantalum or Platinum that forms a continuous material layer sandwiched between the inner coating and the outer coating.
  • the radiopaque material can include or be a multiplicity of radiopaque particles dispersed within the outer coating.
  • the outer coating can include one or more of parylene C, polylactic acid, polyglycolic acid, copolymers of lactic and glycolic acid, polycaprolactone, parylene, polymethacrylate, cyanoacrylates, polyvinylidene fluoride (PVDF), Poly(hydroxyalkanoate) (PHA), and polyurethane, and copolymers of polyurethane.
  • PVDF polyvinylidene fluoride
  • PHA Poly(hydroxyalkanoate)
  • polyurethane and copolymers of polyurethane.
  • the outer coating can carry a therapeutic substance, e.g., an anti-restenosis drug, which can be selected from the group of paclitaxel and its derivatives (e.g., taxane derivatives of paclitaxel), or mTOR inhibitors of the LIMUS family.
  • a therapeutic substance e.g., an anti-restenosis drug
  • an anti-restenosis drug which can be selected from the group of paclitaxel and its derivatives (e.g., taxane derivatives of paclitaxel), or mTOR inhibitors of the LIMUS family.
  • the scaffold can include or be formed as a plurality of radial support rings axially disposed along the length of the scaffold structure, wherein the central axis of the scaffold structure extends through each radial support ring, and wherein each radial support ring includes: a pair of axially adjacent struts radially disposed about the central axis; and a plurality of bridge members, wherein each bridge member couples each of the pair of adjacent struts; and a plurality of preferentially fracturable links (e.g., preferentially fracturable axial links configured for axial coupling radial support rings) wherein each preferentially fracturable link has a length, wherein each preferentially fracturable link couples a pair of adjacent radial support rings, and wherein each preferentially fracturable link includes at least one bent or curved rupture region that is mechanically weaker than each strut and each bridge member of the adjacent radial support rings that it couples.
  • Portions of the inner coating that overlay the preferentially fracturable links can be configured to tear, break, rupture, open, and/or become porous in response to fracture or breakage of the preferentially fracturable links.
  • At least some of the plurality of preferentially fracturable links can have an omega shape along their length.
  • At least some of the bridge members can be a straight structure that extends in a direction parallel to the central axis.
  • a scaffold structure which is implantable into an anatomical lumen of a human or animal body.
  • the scaffold structure is an elongate structure having a length.
  • a central axis is definable through or internal to the elongate scaffold structure along its length.
  • the scaffold structure as-manufactured includes, is formed as, consists essentially of, or consists of: (a) an elongate biodegradable metallic scaffold that provides a frame or cage structure, wherein the scaffold includes, is formed as, consists essentially of, or consists of: (i) a plurality of radial support rings axially disposed along the length of the scaffold, wherein the central axis of the scaffold extends through each radial support ring, and wherein each radial support ring includes, is formed as, consists essentially of, or consists of: a plurality (e.g., a pair) of axially adjacent struts radially disposed about the central axis; and a plurality of bridge members, wherein each bridge member couples each of the plurality of adjacent struts; and (ii) a plurality of preferentially fracturable links (e.g., preferentially fracturable axial links), wherein each preferentially fracturable link has
  • Portions of the inner coating that overlay preferentially fracturable links can be configured to tear, break, rupture, open, and/or become porous in response to fracture or breakage of the preferentially fracturable links.
  • an elongate scaffold which is implantable into an anatomical lumen of a human or animal body.
  • the elongate scaffold has a length, and a central axis is definable through or internal to the elongate scaffold along its length.
  • the scaffold includes, is formed as, consists essentially of, or consists of: a plurality of radial support rings axially disposed along the length of the scaffold, wherein the central axis of the scaffold extends through each radial support ring, and wherein each radial support ring includes, is formed as, consists essentially of, or consist of: a plurality (e.g., a pair) of axially adjacent struts radially disposed about the central axis; and a plurality of bridge members, wherein each bridge member couples each of the plurality of axially adjacent struts; and a plurality of preferentially fracturable links (e.g., preferentially fracturable axial links), wherein each preferentially fracturable link has a length, wherein each preferentially fracturable link couples a pair of adjacent radial support rings, and wherein each preferentially fracturable link includes at least one curved rupture region that is mechanically
  • At least some of the plurality of preferentially fracturable links can have an omega shape along their length.
  • At least some of the bridge members can have a straight structure that extends in a direction parallel to the central axis.
  • a process for manufacturing or providing a biodegradable implantable or implanted metallic scaffold structure configurable or configured for implantation into a mammalian body includes or consists essentially of: providing an elongate biodegradable metallic scaffold having (a) preferentially fracturable links, and (b) radial support rings that are disposed along the scaffold's length and which are coupled by way of the preferentially fracturable links (e.g., preferentially fracturable axial links), wherein the preferentially fracturable links are intentionally (i) configured to be structurally weaker than the radial support rings along at least one spatial direction, and (ii) preferentially fracturable or breakable relative to the radial support rings in response to physical stresses or deformations exerted upon the scaffold; providing or disposing a non- porous first covering or coating over the scaffold, wherein the first covering or coating includes or is a non-biodegradable polymer that conformally encases the
  • FIG. 1 shows portions of a magnesium (Mg) stent constructed with a radiopaque coating as described in U.S. Patent 6,174,329, which results in a radiopaque coating exhibiting flaking or peeling away from the Mg stent.
  • Mg magnesium
  • FIG. 2 is an angiographic image of a Mg scaffold having a radiopaque material directly in contact with the Mg, and which further includes an outer protective layer, at an in vivo post- implantation time of 4 weeks, showing a large amount of restenosis in the region in which the scaffold was implanted, despite the outer protective layer.
  • FIG. 3 shows an idealized degradation time and radial strength curves for a commercially available Mg bioresorbable scaffold or stent.
  • FIG. 4A shows an intraluminal optical coherence tomography (OCT) image of a newly implanted commercially available Mg bioresorbable scaffold in a human coronary artery.
  • OCT optical coherence tomography
  • FIG. 4B shows an early failure of the implanted scaffold of FIG. 4A at 4 months due to biodegradable coating failure and undesirably rapid degradation, leading to breakup of scaffold struts, and resulting in severe restenosis and vessel failure.
  • FIG. 5 is a collection of OCT images showing time progress of strut degradation in a commercially available bioresorbable stent with a prior art biodegradable coating, where there is heterogeneous progression of strut degradation, undesirably resulting in variable radial support by different portions of the stent over time.
  • FIG. 6A is a perspective schematic illustration of a scaffold structure in accordance with an embodiment of the present disclosure.
  • FIG. 6B is a top schematic illustration showing portions of the scaffold structure of FIG. 6A.
  • FIG. 7A is a cross-sectional schematic illustration of a portion of a scaffold structure corresponding to FIGs. 6A - 6B, showing an organization of multiple coatings accordance with a first set of embodiments of the present disclosure, taken along line A - A' of FIG. 6A.
  • FIG. 7B is a cross-sectional schematic illustration of a portion of a scaffold structure corresponding to FIGs. 6A - 6B, showing another organization of multiple coatings in accordance with a second set of embodiments of the present disclosure, taken along line A -A' of FIG. 6A.
  • FIG. 8 is a magnified image showing portions of a scaffold structure in accordance with an embodiment of the present disclosure, which has undergone scaffold expansion, and for which no obvious cracking or flaking or peeling is apparent.
  • FIG. 9 is an in vivo angiographic image of a Mg biodegradable scaffold structure corresponding to FIGs. 6A, 6B, and 7A, which has been implanted in a porcine coronary artery, at a time of 4 weeks post-implantation.
  • FIG. 10A is a Faxitron (X-ray) image of a scaffold structure in accordance with an embodiment of the present disclosure, after 4 weeks of implantation in vivo in a porcine coronary artery, showing several broken or dismantled preferentially fracturable links (e.g., preferentially fracturable axial links).
  • preferentially fracturable links e.g., preferentially fracturable axial links
  • FIG. 10B is an Optical Coherence Tomography (OCT) image in the vessel where the scaffold structure of FIG. 10A is located, demonstrating excellent patency and freedom from restenosis at 4 weeks post-implantation.
  • FIG. 10C is another Faxitron (X-ray) image of a scaffold structure in accordance with an embodiment of the present disclosure, after 12 weeks of implantation in vivo in a porcine coronary artery, showing further dismantling of the preferentially fracturable links.
  • OCT Optical Coherence Tomography
  • FIG. 10D is a 12 week post-implantation OCT image of the vessel where the scaffold structure of FIG. 10C is located, where the results again demonstrate unobstructed blood flow and freedom from restenosis.
  • FIGs. included herewith show aspects of non-limiting representative embodiments in accordance with the present disclosure for purpose of illustration and to aid understanding. Particular structural elements shown in one or more FIGs. may not be to scale or precisely to scale relative to each other.
  • the depiction of a given element or consideration or use of a particular element number in a particular FIG. or a reference thereto in corresponding descriptive material can encompass or relate to a categorically related, the same, an equivalent, or an analogous structure, element, sub-element, or element number identified in another FIG. or descriptive material associated therewith.
  • the presence of "/" in a FIG. or text herein is understood to mean “and/or” unless otherwise indicated.
  • the recitation of a particular numerical value or value range, and use of the term approximately or about in association therewith, is understood to include or be numerical values within +/- 20%, +/- 15%, +/- 10%, +/- 5%, +/- 2.5%, +/- 2%, +/- 1%, +/- 0.5%, or +/- 0% of the recited numerical value or value range.
  • the term essentially can indicate a percentage greater than or equal to 90%, for instance, 92.5%, 95%, 97.5%, 99%, or 100%.
  • a set corresponds to or is defined as a non-empty finite organization of elements that mathematically exhibits a cardinality of at least 1 (i.e., a set as defined herein can correspond to a unit, singlet, or single element set, or a multiple element set), in accordance with known mathematical definitions (for instance, in a manner corresponding to that described in An introduction to Mathematical Reasoning: Numbers, Sets, and Functions , "Chapter 11 : Properties of Finite Sets" (e.g., as indicated on p. 140), by Peter J. Eccles, Cambridge University Press (1998)).
  • a set includes at least one element.
  • an element of a set can include or be one or more portions of a system, an apparatus, a device, a structure, an object, a process, a physical parameter, or a value depending upon the type of set under consideration.
  • a scaffold structure or device e.g., a stent structure or device
  • a stent structure or device that is implantable in a lumen of a living body (e.g., a lumen or anatomical passage, such as a portion of the cardiovascular system, of a human or animal body)
  • which as-manufactured includes: (i) a biodegradable, radiolucent scaffold body which provides or establishes a frame or cage that serves as a structural foundation or substrate upon or outside of which (ii) a first, inner, or innermost material composition, material, coating, layer, or film resides, which includes a non- biodegradable material, and which isolates, separates, and/or insulates (e.g., electrochemically insulates) the scaffold body from each of (iii) a radiopaque material composition, material, coating, layer, or film, and (iv) an outer, outermost, protective, or anti-flaking material composition, material,
  • the scaffold body or the frame or cage corresponding thereto or defined thereby may be referred to as a scaffold; the inner material composition, material, coating, layer, or film may be referred to as an inner coating; and the outer material composition, material, coating, layer, or film may be referred to as an outer coating, in a manner readily understood by individuals having ordinary skill in the relevant art.
  • a scaffold structure or device is typically an elongate structure having a length (e.g., a predetermined, as-designed, or as-manufactured average or uncompressed length).
  • a lengthwise, longitudinal, or central axis can be defined extending along the scaffold structure's length.
  • the scaffold structure has an expanded or maximum cross-sectional area or diameter (e.g., an average diameter) perpendicular to its central axis.
  • the term axial refers to a direction along or parallel to the central axis; and the term radial refers to a direction transverse or perpendicular to the central axis.
  • the inner coating covers, blankets, sheaths, encapsulates, or encases the scaffold (e.g., the inner coating blankets, encapsulates, or encases the entirety of the scaffold, that is, all surfaces of the scaffold that were exposed to the scaffold's surrounding environment prior to the application of the inner coating to the scaffold), such that the scaffold itself resides beneath, under, or internal to the inner coating.
  • the inner coating of the as-manufactured scaffold structure is thus a non-porous coating.
  • the inner coating physically isolates the scaffold from one or more other coatings or materials that reside over or which are applied or deposited external to or outside or on top of the inner coating.
  • the scaffold resides beneath or under the inner coating (e.g., entirely underneath the inner coating); and the inner coating is disposed beneath or under the radiopaque coating or material(s) and the outer coating.
  • the inner coating electrochemically insulates or isolates the scaffold from electrochemical corrosion that would otherwise occur (e.g., in the presence of water and/or other body fluids) if the radiopaque coating or material(s) were in direct contact with the scaffold.
  • the inner coating establishes a physical barrier (e.g., an electrochemical barrier) with respect to electron transfer between the scaffold and the radiopaque coating or radiopaque material(s).
  • the outer coating surrounds, covers, blankets, sheaths, encapsulates, or encases the radiopaque material(s) and the inner coating, and in multiple embodiments of the as- manufactured scaffold structure, physically isolates the radiopaque material(s) from the scaffold structure's external environment.
  • the outer coating is typically a non-porous coating, although outer coating non-porosity is not required in all embodiments (i.e., in certain embodiments, the outer coating is porous).
  • radiopaque coating and the outer coating are separate or sequentially distinct coatings, e.g., corresponding to or defining two successive or adjacent (e.g., directly adjacent) material films or layers that are formed or applied sequentially or separately relative to each other, where each such material layer has a predetermined thickness and a distinct chemical composition, and each such material layer is typically uniform or essentially uniform throughout its thickness with respect to its chemical composition.
  • At least one material suitable for forming an outer coating e.g., a polymer material
  • one or more radiopaque materials to form a radiopaque first outer coating, film, or layer, to or upon which another layer of outer coating material (e.g., the same or a different polymer material) that excludes the radiopaque material(s) is applied to form a non-radiopaque second outer coating, film, or layer.
  • another layer of outer coating material e.g., the same or a different polymer material
  • the radiopaque first outer coating and the non-radiopaque second outer coating can be referred to or defined as a composite outer coating, film, or layer.
  • the radiopaque first outer coating is typically a film or layer (e.g., a continuous film or layer) in which a polymer material having a predetermined thickness carries one or more types of radiopaque materials or particles (e.g., a multiplicity of radiopaque particles), such that the radiopaque materials or particles are incorporated, distributed, dispersed, or embedded in the polymer material.
  • the non-radiopaque second outer coating is typically a non-porous film or layer that includes or is made of the same or a different polymer material.
  • a scaffold structure (e.g., an as-manufactured scaffold structure) can carry one or more therapeutic agents, or exclude any therapeutic agent, depending upon embodiment details.
  • an outer coating or a composite outer coating can optionally carry one or more therapeutic agents or substances, e.g., to facilitate controlled drug elution, in a manner readily understood by individuals having ordinary skill in the relevant art.
  • the outer coating or composite outer coating includes a therapeutic agent therein, whereas in other embodiments the outer coating or composite outer coating excludes any therapeutic agent therein.
  • a non-porous outer coating or non-porous composite outer coating isolates the radiopaque material(s) from chemical species in the scaffold structure's external environment.
  • the scaffold in a first set of embodiments of an as-manufactured scaffold structure or device, includes or is formed of a biodegradable metal alloy or metal, e.g., magnesium (Mg) or a Mg alloy, over or on top of which a conformal, non-porous inner coating, e.g., of a type set forth herein, resides or is applied or deposited.
  • a biodegradable metal alloy or metal e.g., magnesium (Mg) or a Mg alloy
  • a radiopaque coating resides or is applied or deposited over or on top of the inner coating, and an outer coating (e.g., non-porous outer coating) resides or is applied or deposited over or on top of the radiopaque coating.
  • the outer coating has an outer or exterior surface that forms the outer or exterior surface of the as-manufactured scaffold structure (e.g., the exposed outer surface of the as-manufactured scaffold structure, which is exposed to the scaffold structure's external environment).
  • the inner coating includes or is composed of at least one type of non-biodegradable material, which conformally covers and electrochemically insulates the scaffold from the radiopaque material(s) and thus prevents galvanic corrosion between the scaffold and the radiopaque material(s), while also preventing premature or undesirably rapid biodegradation of the scaffold (e.g., the Mg alloy) when the scaffold is in the presence of, exposed to, or in contact with body fluids.
  • the radiopaque coating enables the scaffold structure to be visualized under fluoroscopy.
  • the outer coating includes or is composed of a biodegradable and/or a non-biodegradable material that prevents the radiopaque coating from cracking and/or flaking or peeling away from or off of the scaffold, e.g., when the crimped scaffold structure is implanted into a vessel along a tortuous pathway, and/or expanded within the vessel during a scaffold structure implantation procedure.
  • the scaffold includes or is formed of a biodegradable metal alloy or metal, e.g., a Mg alloy, which is covered or coated with a conformal non-biodegradable inner coating, e.g., of a type set forth herein.
  • a biodegradable metal alloy or metal e.g., a Mg alloy
  • a conformal non-biodegradable inner coating e.g., of a type set forth herein.
  • the scaffold structure or device includes a composite outer coating of a type set forth herein that is applied over the inner coating; e.g., in the composite outer coating, particles of one or more high atomic weight materials that provide radiopacity are distributed or dispersed throughout a polymer material to form a radiopaque first outer coating, which is overlaid, encased, or encapsulated with the same or a different polymer material (or a combination of polymer materials) to form a non-porous, non-radiopaque second outer coating.
  • the composite outer coating and in particular, the non-radiopaque second outer coating, has an outer or exterior surface that forms the outer or exterior surface of the as-manufactured scaffold structure (e.g., the exposed outer surface of the as- manufactured scaffold structure, which is exposed to the scaffold structure's external environment).
  • the scaffold includes strut members or struts that are radially, annularly, or circumferentially disposed about or around the scaffold's central axis.
  • the struts typically have a serpentine structure about or around the scaffold's central axis.
  • Particular adjacent struts are selectively axially coupled or joined together by bridge members, elements, or links, such that predetermined groups of struts (e.g., particular pairwise-adjacent struts) that are coupled or joined together by way of bridge members form radial support structures, segments, sections, or rings.
  • successive or adjacent radial support rings are axially coupled or joined together by preferentially breakable, fracturable, frangible, or rupturable links (e.g., preferentially fracturable axial links).
  • preferentially fracturable links are at least somewhat flexible and/or resilient with respect to the motion or displacement of the radial support structures or rings coupled or joined thereby.
  • the preferentially fracturable links are typically contiguous, one/single piece, or integral structures.
  • the preferentially fracturable links enable and accommodate at least some displacement (e.g., longitudinal, lengthwise, or axial displacement) of adjacent radial support rings relative to each other, and thus enable and accommodate at least some variability in spacing between adjacent radial support rings, particularly during scaffold structure expansion.
  • a preferentially fracturable link can structurally correspond to or be defined as a type of flat spring structure.
  • the scaffold structure includes multiple radial support rings that are axially coupled or connected together by way of flat spring structures, where the flat spring structures include or are implemented as preferentially fracturable links.
  • the preferentially fracturable links are intentionally designed or structurally configured to include one or more rupture sections or regions that are structurally weaker or more prone to structural failure (e.g., in response to scaffold structure motion, deformation, or flexure, such as on a repeated or repetitive basis) than each strut and each bridge member.
  • the weaker / weakest portions of a scaffold in accordance with various embodiments of the present disclosure are the rupture regions of the preferentially fracturable axial links.
  • Such fracturable links are thus preferentially or more readily fracturable or more prone to structural failure compared to the fracturability or structural failure likelihood of the struts and the bridge members.
  • the preferentially fracturable links are intentionally designed such that they are more or much more likely to fracture (or fracture earlier) than the struts and the bridge members (e.g., in response to physical or mechanical stresses) exerted upon the scaffold structure.
  • its rupture region(s) can be provided by at least one bent, curved, or curvilinear portion or segment along the preferentially fracturable axial link's length.
  • At least some preferentially fracturable links generally exhibit or have an omega-type lengthwise profile or shape (e.g., a contiguous, one/single piece, or integral omega shape or profile); however, in other embodiments, at least some preferentially fracturable links can generally exhibit or have a c-shaped, u-shaped, v-shaped, w-shaped, s-shaped, or similar or other type of lengthwise profile or shape. In embodiments in which the preferentially fracturable links have an omega-type lengthwise shape, the height to width ratio of the omega shape is typically at least approximately 1.5.
  • the physical structure of the scaffold, and in particular the preferentially fracturable links coupling the scaffold's radial support rings, in combination with the physical nature, properties, or composition and organization of the coatings carried by the scaffold as set forth herein, enables the preferential axial decoupling of the scaffold's radial support rings (e.g., the preferential decoupling of particular or particular subsets of radial support rings) over a predictable or controllable period of time before significant degradation (e.g., biodegradation) of the scaffold's strut elements and bridge members occurs.
  • the inner coating includes or is a non-biodegradable coating having sufficient thickness and uniformity relative to the topology of the scaffold such that the inner coating prevents scaffold biodegradation prior to the breakage of any preferentially fracturable links. More particularly, for an as-manufactured scaffold structure or device, the inner coating conformally covers the scaffold in a pinhole-free or essentially pinhole-free manner, and prevents the ingress of chemical species, which could or would cause scaffold material degradation, to or into the scaffold material. Prior to the breakage or rupture of any preferentially fracturable links, the inner coating over the entire scaffold structure or device thus prevents scaffold degradation.
  • first preferentially fracturable link e.g., a first preferentially fracturable axial link
  • first broken link e.g., corresponding to or forming two separate link pieces or segments that were formerly contiguous or integral
  • fluids e.g., body fluids
  • chemical species e.g., chemical species in the environment in which the scaffold structure or device resides, and thus portions of the scaffold at and along this broken link can begin to degrade (e.g., this broken link can begin to progressively biodegrade along its length, starting from its terminal ends or end portions).
  • the overall time required for scaffold degradation is significantly or very significantly longer than that for prior art scaffold structures (e.g., by at least a factor of approximately 2 - 4).
  • the inner coating of the as-manufactured scaffold structure should be sufficiently thick such that immediately after implantation in a vessel and for an intended, desired, or target time period thereafter, it prevents galvanic corrosion between the radial support rings of the scaffold and the radiopaque material(s) used to provide scaffold structure radiopacity.
  • the inner coating should not be so thick that it inhibits the gradual or very gradual biodegradation of the scaffold once an intended, desired, target, or sufficient extent of cell endothelization has taken place or is expected to have taken place in the vessel.
  • endothelial tissue can grow around and/or into portions of the scaffold structure (e.g., around radial support rings or portions thereof that remain covered by the aforementioned coatings), such that non-degradable portions of the scaffold structure (e.g., the inner coating, and the radiopaque material(s)) become physically embedded or incorporated into vessel tissue.
  • the inner coating can remain as a thin biocompatible layer within vessel tissue.
  • the axial decoupling mechanism by which the scaffold's radial support rings become physically decoupled or detached from each other, in conjunction with (b) the composition and organization of the coatings, significantly and predictably or controllably reduce or slow the scaffold's degradation rate, and cooperatively or synergistically aid or enable (i) the restoration of vessel flexibility and enhancement of the natural pulsatile function of the vessel over time, and ensure that (ii) individual radial support rings provide sufficient radial support to the vessel during or over an intended, adequate, target, or predetermined period of time that intentionally corresponds to or is correlated with the likely or expected duration of the vessel's healing phase.
  • Embodiments in accordance with the present disclosure are applicable to endovascular treatment of vascular and non-vascular diseases in coronary arteries and various peripheral vessels including the tibial artery, superficial femoral artery, iliac artery, carotid artery, and renal artery.
  • Embodiments in accordance with the present disclosure are also applicable to non-vascular treatment including the palliation of strictures of the bile ducts (Hepatic, Cystic, Common Bile, and Pancreatic) resulting from malignancy of the liver, pancreas, duodenum, biliary tree, or from various benign diseases.
  • the bile ducts Hepatic, Cystic, Common Bile, and Pancreatic
  • a biodegradable scaffold structure in accordance with an embodiment of the present disclosure is to provide temporary support for a body lumen or portions thereof for an intended, target, predetermined, or minimum time period, e.g., approximately 3 - 12 months or longer. This will restore the uninterrupted flow of blood and/or other body fluid(s) in the body lumen, and at the same time facilitate the formation of endothelial tissue around portions of the scaffold structure (which takes place across a 1- 3 month time period according to animal tests), thereby enabling portions of the scaffold structure (e.g., non-resorbable portions of the scaffold structure) to be integrated into the vessel wall, while the scaffold itself slowly degrades and reduces its mechanical strength properties.
  • an intended, target, predetermined, or minimum time period e.g., approximately 3 - 12 months or longer.
  • a biodegradable or bioresorbable scaffold can include or be formed of a metallic material such as one or more of magnesium (Mg), iron (Fe), zinc (Zn), alloys of these metals, or similar materials.
  • the bioresorbable scaffold includes or is formed of a Mg alloy because of its low thrombogenicity and well- known biocompatibility, as Mg alloys have been used in many orthopedic and cardiovascular implant structures, devices, and applications. Suitable Mg alloys for use in embodiments in accordance with the present disclosure are described in U.S. Patent Nos. 9,522,219; 9,566,367; and 8,507,101, each of which is incorporated herein by reference in its entirety.
  • Mg has limited its use in bioresorbable scaffolds.
  • With respect to commercially-available Mg- based scaffolds despite protecting the Mg with a coating or layer of Polylactide-based polymer, isolated clinical cases of unintended / uncontrolled acute localized scaffold degradation (occurring over a time period of less than 6 months) have been reported, likely due to the polymer layer being partially compromised.
  • a coating over the scaffold with a layer of a suitable high atomic weight element, compound, or material enables the scaffold to achieve sufficient radiopacity, but does not obstruct the visualization of radiopaque dye during fluoroscopy.
  • the coating can be high atomic weight material such as tantalum (Ta), gold (Au), platinum (Pt), bismuth (Bi), iridium (Ir), or the like.
  • Au has a better ductility property
  • the results of human clinical trials of a Au coated stent have demonstrated that the Au coated stent induced higher neointimal hyperplasia as compared to an uncoated stainless steel stent.
  • Ta or Pt is thus a better choice for a radiopaque material or coating in various embodiments of the present disclosure, because of high atomic weight and density which contributes to radiopacity, as well as good or excellent biocompatibility.
  • an inner or inner insulation coating between the scaffold and the radiopaque (e.g., Ta or Pt) coating or layer is applied to reduce or minimize the likelihood of scaffold galvanic corrosion.
  • an outmost coating or outermost protective layer is applied to prevent the radiopaque (e.g., Ta or Pt) layer from cracking or flaking off.
  • FIGs. 6A - 6B and 7A - 7B show aspects of radiopaque metallic bioresorbable scaffold structures or devices (e.g., stent structures or devices) 10 in accordance with particular embodiments of the present disclosure. More specifically, FIG. 6A is a perspective schematic illustration of a scaffold structure 10, which includes or is formed from a scaffold that underlies a non-degradable inner coating, where the inner coating itself underlies a radiopaque coating or material(s) and an outer coating or composite outer coating, as further detailed below.
  • the scaffold structure 10 has a length (e.g., an average or predetermined uncompressed length), and a lengthwise, longitudinal, or central axis 5 can be defined therethrough along the scaffold structure's length.
  • the scaffold structure 10 also has an expanded or maximum cross-sectional area or average cross-sectional area (e.g., a generally uniform or uniform cross-sectional area or diameter) along its length about the central axis 5.
  • FIG. 6B is a top schematic illustration showing portions of the scaffold structure 10 of FIG. 6A.
  • FIG. 7A is a cross-sectional schematic illustration of a portion of a scaffold structure 10a in showing an organization of multiple coatings accordance with a first set of embodiments corresponding to FIGs. 6A - 6B, taken along line A - A' of FIG. 6A; and FIG. 7B is a cross- sectional schematic illustration of a portion of a scaffold structure 10b showing another organization of multiple coatings in accordance with a second set of embodiments corresponding to FIGs. 6A - 6B, taken along line A - A' of FIG. 6A.
  • the scaffold structure 10 of FIGs. 6A - 6B includes an underlying or innermost biodegradable metallic scaffold 100, e.g., which (a) forms an inner frame or cage that extends along the scaffold structure's length; (b) can be defined as the as-manufactured scaffold-structure's inner core; and (c) gives rise to the scaffold structure's overall lengthwise or longitudinal geometry or shape, in a manner readily understood by individuals having ordinary skill in the relevant art.
  • the scaffold 100 is fabricated or manufactured by known processes such as laser cutting from a tube, or mesh weaving using wires, in a manner also readily understood by individuals having ordinary skill in the relevant art.
  • the scaffold 100 and thus the scaffold structure 10 includes radially expandable / compressible struts 110 disposed about or around the central axis 5, which typically exhibit a serpentine shape or pattern about or around the central axis 5.
  • Individual struts 110 contribute to the scaffold structure's radial strength.
  • the struts 110 provide radial support to the walls of an anatomical passage or vessel in which the scaffold structure 10 is implanted, in a manner readily understood by individuals having ordinary skill in the relevant art.
  • Predetermined pairs of directly adjacent struts 110 are coupled or connected by bridge members 120 to form radial support rings 130, which further enhance or maximize the scaffold structure's radial strength.
  • the bridge members 120 are typically linear or straight structures, which typically extend in a direction parallel to the central axis 5, though this need not be the case in all embodiments (e.g., portions of some bridge members 120 can be oriented at an angle with respect to the central axis 5).
  • the two struts 110 thereof are coupled or connected (e.g., axially coupled or connected) by a total of six bridge members 120 disposed at predetermined positions about or around the central axis 5.
  • At least some radial support rings 130 can have fewer or additional bridge members 130 that couple or connect the struts 110 thereof. Also, while each radial support ring 130 has two struts 110 in FIG. 6A, in alternate embodiments one or more radial support rings 130 can include more than two struts 110 (e.g., three struts 110).
  • Radial support rings 130 that are directly adjacent to each other are longitudinally or axially coupled or connected to each other, i.e., coupled or connected along a direction extending parallel to the central axis 5, by way of intentionally / preferentially fracturable links, e.g., intentionally / preferentially fracturable axial links 140 (which for purpose of simplicity can be referred to hereafter as preferentially fracturable links 140).
  • Each preferentially fracturable link 140 includes or is a bent, curved, or curvilinear structure having at least one rupture region 142.
  • At least some preferentially fracturable links 140 are formed as contiguous, one/ single piece, or integral structures (e.g., each preferentially fracturable link 140 is a contiguous, one/single piece, or integral structure).
  • the rupture region 142 of a preferentially fracturable link 140 includes, provides, or forms a curvature inflection segment or vertex along the link 140; and the curvature inflection segments or vertices of one or more preferentially fracturable links 140 (e.g., each such link 140) can be oriented or pointed in a direction transverse or perpendicular to the central axis 5.
  • At least some preferentially fracturable links 140, or each preferentially fracturable link 140 includes or is formed to have a lengthwise shape or profile that corresponds or generally corresponds to or resembles an omega (W) shape, although preferentially fracturable links 140 can have other or additional types of lengthwise curved shapes or profiles in other embodiments.
  • W omega
  • preferentially fracturable links 140 can have other or additional types of lengthwise curved shapes or profiles in other embodiments.
  • FIG. 6A - 6B in which the preferentially fracturable links 140 exhibit a lengthwise omega-type of shape, as indicated in FIG.
  • such preferentially fracturable links 140 can include a first or central rupture region 142 corresponding to a first, middle, or more gently curved portion of the omega shape, and one or more additional rupture regions 143 corresponding to additional, extremity, or more sharply curved portions of the omega shape.
  • pairwise adjacent radial support rings 130 are coupled or connected by a total of three preferentially fracturable links 140 disposed at predetermined locations about or around the central axis 5.
  • at least some pairwise adjacent radial support rings 130 can be coupled or connected by fewer or additional preferentially fracturable links
  • the scaffold 100 When the scaffold structure 10 is expanded and deployed in a vessel, the scaffold 100, and in particular the struts 110 (and hence the radial support rings 130) and the preferentially fracturable links 140 undergo plastic deformation.
  • the scaffold 100 In order to achieve an intended, desired, or target performance of the scaffold structure 10 in view of sustained radial strength, anti- corrosion properties, radiopacity, body fluid / blood compatibility, and intended, desired, target, or optimum degradation rate, multiple coatings, layer, material compositions, or materials are applied over the scaffold, in a specific predetermined order.
  • an inner coating 20 is applied to coat the entirety of the exposed surface are of the scaffold 100, that is, both inward / internal facing surfaces (i.e., facing toward the central axis 5) and outward / external facing surfaces (i.e., facing away from the central axis 5) of the scaffold 100.
  • the inner coating 20 should be sufficiently thick to prevent galvanic corrosion from taking place between the biodegradable metal (e.g., Mg) of the scaffold 100 and radiopaque material(s) that are carried by the scaffold structure 10.
  • the inner coating 20 should not be so thick that it inhibits the intended gradual, very gradual, or predictably gradual degradation or breakdown of the biodegradable metal (e.g., Mg) scaffold 100 once sufficient cell endothelization has taken place in the vessel.
  • the inner coating 20 has a thickness (e.g., a generally uniform or uniform thickness) between approximately 0.1 to 10 micrometers (e.g., in some embodiments, less than or equal to: approximately 5 micrometers, or 4 micrometers, or 3 micrometers, or 2 micrometers; or between: approximately 0.1 - 3.0 micrometers, or approximately 0.5 - 3.0 micrometers, or approximately 1 - 3 micrometers).
  • the inner coating 20 not be too rigidly adhered or attached to the scaffold 100, but rather forms a stretchable or suitably stretchable / resilient sheath covering the scaffold 100 with adequate resilience during scaffold expansion, preferentially fracturable link deformation, and radial support ring detachment, as further detailed below.
  • a radiopaque coating 30 is applied or deposited on top of the inner coating 20.
  • the radiopaque coating 30 typically has a thickness between approximately 1 - 10 micrometers. In this thickness range, the radiopaque coating provides sufficient radiopacity to allow the scaffold structure 10 to be seen under fluoroscopy, while maintaining a sufficiently thin coating that does not or does not significantly adversely affect the scaffold structure's mechanical properties, especially the expandability and flexibility of the scaffold 100.
  • the radiopaque coating 30 can be applied to the inner / internal and/or outer / external surface(s) of the scaffold 100 following the application of the inner coating 20 to the scaffold 100.
  • the radiopaque coating 30 can be applied by way of magnetron sputtering, physical vapor deposition (PVD), chemical vapor deposition, dipping, ion implantation, or other techniques known in the art.
  • PVD physical vapor deposition
  • a typical magnetron sputtering process for applying the radiopaque layer 30 involves fixing the scaffold 100 in a fixture that is electrically conductive, and then placing it in sputtering chamber that is subjected to a negative or vacuum pressure lower than 8x10 -6 torr, e.g., typically lower than 4x10 -7 torr, before commencing a radiopaque layer coating process, which typically involves multiple sputtering sessions.
  • the radiopaque layer coating can be carried out at room temperature, with a rest period between each sputtering session of approximately 30 minutes in order to prevent the scaffold surface temperature from being elevated above a temperature of more than about 80°C.
  • the entire radiopaque layer coating process including attaining a target vacuum pressure, takes approximately 5-10 hours depending on the sputtering chamber size, and the sputtering target material condition and thickness.
  • An outer coating 40 is applied or deposited on top of the radiopaque coating 30.
  • the outer coating 40 typically has a thickness between approximately 1 - 10 microns, and protects the radiopaque coating 30 from cracking and/or flaking off as the scaffold structure 10 is delivered through a tortuous vessel shape and subsequently expanded in the vessel at a lesion site.
  • the outer coating 40 can be a single layer coating, or a multi-layer coating.
  • the inner coating 20 is biocompatible and in various embodiments is non-biodegradable, and is able to provide sufficient insulation or electrochemical isolation between the scaffold 100 and the radiopaque coating 30 to prevent galvanic corrosion of the scaffold 100.
  • the inner coating 20 can include or be one or more materials such as parylene, polymethacrylate and its copolymers, polyvinyl acetate, and polycaprolactone.
  • the inner coating 20 includes or is made of parylene, as it is important for the inner coating 30 to be a pinhole free, conformal layer. In prior art stent applications, parylene has been mainly used in conjunction with other surface treatments to form an adhesion layer to enhance the adhesion of a second polymer layer to the stent.
  • the outer coating 40 is biocompatible, and may or may not be biodegradable.
  • the outer coating 40 provides protection for the radiopaque coating 30.
  • the outer coating 40 can include or be formed of one or more polymeric materials, such as polylactic acid, polyglycolic acid, copolymers of lactic and glycolic acid, polycaprolactone, parylene, polymethacrylate, polyvinylidene fluoride (PVDF), poly(hydroxyalkanoate) (PHA), cyanoacrylates and its copolymers, and polyurethane and its copolymers.
  • PVDF polyvinylidene fluoride
  • PHA poly(hydroxyalkanoate)
  • cyanoacrylates and its copolymers and polyurethane and its copolymers
  • An additional or other material such as diamond-like carbon (DLC), which has good biocompatibility characteristics, is also suitable.
  • DLC diamond-like carbon
  • the outer coating 40 includes or is formed of parylene, as parylene is able to provide a pinhole free, conformal layer.
  • the outer coating 40 is able to provide sufficient protection for the radiopaque coating 30 so as to prevent the radiopaque coating 30 from flaking off during scaffold implantation and expansion. Due to the biodegradable nature of polylactic acid, upon sufficient endothelization around the scaffold structure 10, the polylactic acid of the outer coating 40 will slowly degrade, and hence will assist in the gradual degradation of the scaffold structure 10.
  • the outer coating 40 can be applied by dip-coating, spray-coating, spin-coating, plasma deposition, pipetting, condensation, electrochemically, electrostatically, or other suitable techniques.
  • the outer coating 40 or particular portions of the outer coating 40 can serve as a reservoir for one or more therapeutic substances or drugs that allow controlled release of the therapeutic agent(s).
  • the therapeutic agent is present within and/or upon the outer coating 40 along the entirety of the scaffold structure's length.
  • the therapeutic agent is carried by the outer coating 40 only along particular portions of the scaffold structure's length, but is absent or excluded from the outer coating 40 along other portions of the scaffold structure's length.
  • the therapeutic agent can be present in the outer coating 40 over the radial support rings 130, but absent from the outer coating 40 over the preferentially fracturable links 140.
  • a first therapeutic agent can be carried by the outer coating 40 over particular portions of the scaffold structure's length, and a second therapeutic agent that is different from the first therapeutic agent with respect to chemical composition and/or concentration can be carried by the outer coating 40 over other portions of the scaffold structure's length.
  • the first therapeutic agent can be carried by the outer coating 40 over the radial support rings 130, and the second therapeutic agent can be carried by the outer coating 40 over the preferentially fracturable links 140.
  • FIG 7B shows another scaffold structure coating organization, in which the scaffold structure 10b has a composite outer coating over the inner coating 20, where the composite outer coating includes or is formed as a radiopaque first outer coating 35 and a non-radiopaque second outer coating 40.
  • radiopaque particles e.g., Ta or Pt particles
  • a material e.g., a polymer material
  • the Ta or Pt particles a size of or ranging between approximately 0.1 - 10 microns are mixed (e.g., premixed) with a coating material such as polylactic acid, polyglycolic acid, copolymers of lactic and glycolic acid, polycaprolactone, parylene, polymethacrylate, cyanoacrylates, polyvinylidene fluoride (PVDF), poly(hydroxyalkanoate) (PHA), or polyurethane and associated copolymers.
  • a coating material such as polylactic acid, polyglycolic acid, copolymers of lactic and glycolic acid, polycaprolactone, parylene, polymethacrylate, cyanoacrylates, polyvinylidene fluoride (PVDF), poly(hydroxyalkanoate) (PHA), or polyurethane and associated copolymers.
  • the polymer material with radiopaque particles distributed or dispersed therein can applied by a standard coating technique, such as dip-coating or spray-coating, to obtain a uniform coating thickness for the radiopaque first outer coating 35 onto or over the outer, exterior, or exposed surface(s) of the inner coating 20.
  • the radiopaque first outer coating 35 can be formed by way of micro-pipetting of a polymer coating material with radiopaque particles distributed or dispersed therein onto or over the outer, exterior, or exposed surface(s) of the inner coating 20.
  • the non-radiopaque second outer coating 40 is then applied over the radiopaque first outer coating 35, e.g., in a manner identical, essentially identical, or analogous to that described in the previous paragraph.
  • the non- radiopaque second outer coating 40 is typically non-porous, and in various embodiments, the radiopaque first outer coating is also non-porous.
  • the inner coating 20 prevents direct contact between the radiopaque particles of the radiopaque first outer coating 35 and the Mg scaffold 100, and hence prevents galvanic corrosion or unintended or excessive galvanic corrosion of the scaffold 100; and the non-radiopaque second outer coating 40 prevents chemical substances or species in the scaffold structure's external environment from interacting with or contacting the radiopaque particles of the radiopaque first outer coating 35.
  • an important aspect of embodiments in accordance with the present disclosure is the organization or sequence of coatings carried by or applied to the biodegradable metallic scaffold 100, which is crucial for the clinical success of the biodegradable metallic scaffold 100 in order to avoid or prevent radiopaque material cracking and/or flaking, prevent unintended or excessive scaffold galvanic corrosion, and also to enable a controlled biodegradation or bioresorption / breakdown of the scaffold 100.
  • the coating sequence is such that the inner coating 20 covers the scaffold 100, and the radiopaque coating 30 is sandwiched in between the inner coating 20 and the outer coating 40.
  • the coating sequence is such that the inner coating 20 is applied over the scaffold 100, and the composite outer coating is applied over the inner coating 20, e.g., by way of the application of the radiopaque first outer coating 35 over the inner coating 20, followed by the application of the non-radiopaque second outer coating 40 over the radiopaque first outer coating 35.
  • FIG. 8 is a magnified image showing portions of a scaffold structure 10 in accordance with an embodiment of the present disclosure, which has undergone scaffold expansion. As shown in FIG. 8, no obvious cracking or flaking is apparent, and thus the coatings carried by the scaffold 100 remain intact following scaffold expansion.
  • FIG. 9 is an in vivo angiographic image of a Mg biodegradable scaffold structure 10 in accordance with the embodiment shown in FIGs. 6A, 6B, and 7A, which has been implanted in a porcine coronary artery, at a time of 4 weeks post-implantation.
  • the coronary artery remains fully open, with no sign of vessel narrowing due to restenosis or excessive tissue response. It should be noted that after 12 weeks of in vivo implantation, the coronary artery remains also open with no sign of vessel narrowing due to restenosis or excessive inflammatory or other tissue response.
  • the scaffold structure 10 is crimped onto a balloon catheter and delivered through a guidewire, after which the scaffold structure 10 is subsequently expanded and deployed in the body vessel.
  • the scaffold structure 10 experiences or undergoes significant deformation.
  • the scaffold structure 10 experiences generally constant radial pressure, together with the natural pulsatile flexing of the vessel.
  • the apex of the omega-shape was typically the area or portion of the preferentially fracturable links 140 that experienced the highest concentration of mechanical stress.
  • the height to width ratio of the omega shape is at least approximately 1.5.
  • FIG. 10A is a Faxitron (X-ray) image of a scaffold structure 10 in accordance with an embodiment of the present disclosure, after 4 weeks of implantation in vivo in a porcine coronary artery. As indicated in FIG. 10A, several broken or dismantled preferentially fracturable links 140 can be seen, while the strut 110 and the bridge members 120, and hence the radial support rings 130, remain intact.
  • FIG. 10B is a corresponding Optical Coherence Tomography (OCT) image in the vessel where the scaffold structure 10 of FIG. 10A is located, demonstrating excellent patency and freedom from restenosis, and where the scaffold structure 10 was essentially completely or completely endothelized, at 4 weeks post-implantation.
  • OCT Optical Coherence Tomography
  • the breakage or dismantling of the preferentially fracturable links 140 does not lead to localized accelerated degradation of the scaffold 100 (e.g., accelerated or significantly accelerated degradation of the radial support rings 130), which is prevented by the coatings in accordance with embodiments of the present disclosure, particularly by way of the inner coating 20 that is applied in the absence of or without surface adhesive treatments to the Mg scaffold 100 to thereby allow the inner coating 20 to act as an impermeable yet flexible and resilient sheath that can adapt to or flexibly / slidably accommodate the various movements of the scaffold 100 underlying the inner coating 20.
  • FIG. 10C is another Faxitron (X-ray) image of a scaffold structure 10 in accordance with an embodiment of the present disclosure, after 12 weeks of implantation in vivo in porcine coronary artery.
  • the dismantling of the preferentially fracturable links 140 is clearly more pronounced at 12 weeks, while the struts 110 and the bridge members 120 (and hence the radial support rings 130) remain intact.
  • FIG. 10D is a corresponding 12 week post- implantation OCT image of the vessel where the scaffold structure 10 is located, where the results again demonstrate unobstructed blood flow and freedom from restenosis.
  • the mechanical strength of the preferentially fracturable links 140 is selected or established such that no more than approximately 5% of the preferentially fracturable links 140 break in association with or during a scaffold structure implantation procedure (e.g., as a result of scaffold structure expansion during implantation). Additionally, the mechanical strength of the preferentially fracturable links 140 can be selected or established such that approximately 20-40% (e.g., about 30%) of the of the preferentially fracturable links 140 become fractured at approximately 4 weeks post-implantation; and approximately 50% or more of the preferentially fracturable links 140 become fractured at approximately 12 weeks post- implantation.
  • each individual preferentially fracturable link 140 of the scaffold structure 10 can have an approximately identical mechanical strength; however, in other embodiments, some preferentially fracturable links 140 can be weaker than other preferentially fracturable links 140, e.g., in order to preferentially tailor or customize the likelihood or occurrence of adjacent radial support ring separation at different locations along the scaffold structure's length.
  • This unique radial support ring decoupling or disconnection mechanism provided by various embodiments of the present disclosure can quickly restored the flexibility, and enhance the natural pulsatile function of the vessel while the multiple coatings of the scaffold structure 10 ensure that as portions of the scaffold structure 10 biodegrade over time, the radial support rings 130 of the remaining scaffold structure 10 provide adequate radial support to the vessel.
  • a biodegradable implantable or implanted metallic scaffold structure or scaffold such as a stent configurable or configured for implantation into a mammalian body, and having (a) first structural elements (e.g., preferentially fracturable links 140), and (b) second structural elements (e.g., ring-like or ring-type structures, such as radial support rings 130), wherein the first structural elements are intentionally (i) configured to be structurally weaker than the second structural elements along at least one spatial direction, and (ii) preferentially fracturable or breakable relative to the second structural elements in response to physical stresses or deformations exerted upon the scaffold (e.g., typical physical stresses or deformations that the scaffold structure is expected to experience post-implantation); and (2) a non-porous first or inner covering or coating disposed over the scaffold, wherein the first or inner covering or coating includes or is a non-biodegradable polymer that conformally encase
  • Portions of the first or inner covering or coating that overlay first structural elements of the scaffold are intentionally configured to tear, break, rupture, open, and/or become porous (e.g., by way of thinning and/or stretching) in response or subsequent to fracture or breakage of the first structural elements, thereby exposing portions (e.g., terminal or end portions, regions, or segments) of the fractured or broken first structural elements to a physical environment in which the scaffold structure resides, such as a biological environment in which biodegradation can occur by way of biological fluid incursion or biological fluid / chemical species contact with the fractured or broken first structural elements, which can enable gradual progressive biodegradation of portions of the scaffold structure beginning at such fractured or broken first structural elements that are exposed to such an environment.
  • portions of the first or inner covering or coating that overlay first structural elements of the scaffold are intentionally configured to tear, break, rupture, open, and/or become porous (e.g., by way of thinning and/or stretching) in response or subsequent to fracture or breakage of the first structural elements, thereby
  • a radiopaque material can be disposed external to the first or inner coating along at least portions of the scaffold's length (e.g., along the entire or essentially entire length of the scaffold).
  • a non-porous second or outer coating including a biodegradable or non- biodegradable polymer can be disposed over or external to outer surfaces of the radiopaque material over the scaffold's length (e.g., along the entire or essentially entire length of the scaffold).
  • the first or inner coating electrochemically isolates the radiopaque material from the scaffold.
  • a manufacturing process for a biodegradable implantable or implanted metallic scaffold structure such as a stent configurable or configured for implantation into a mammalian body can include or consist essentially of: providing a biodegradable metallic scaffold having or consisting essentially of (a) first structural elements (e.g., preferentially fracturable links 140), and (b) second structural elements (e.g., ring-like or ring-type structures, such as radial support rings 130), wherein the first structural elements are intentionally (i) configured to be structurally weaker than the second structural elements along at least one spatial direction, and (ii) preferentially fracturable or breakable relative to the second structural elements in response to physical stresses or deformations exerted upon the scaffold (e.g., typical physical stresses or deformations that the scaffold structure is expected to experience post-implantation); providing or disposing a non-porous first or inner covering or coating over the scaffold, wherein the first or inner covering or coating includes or is a non-biodegradable polymer
  • biodegradable scaffold e.g., a biodegradable metallic scaffold such as a biodegradable stent-like structure or stent
  • a biodegradable scaffold having:
  • preferentially fracturable structural elements or links e.g., preferentially fracturable links 140
  • preferentially fracturable structural elements or links that are intentionally configured to be structurally weaker and hence more prone to fracture or breakage in response to physical stress(es) than ring-like or ring-type structures of the scaffold or scaffold structure, such as radial support rings 130, that are coupled or interconnected by the preferentially fracturable structural elements or links;
  • first or inner non-biodegradable inner covering or coating e.g., inner coating 20
  • first or inner non-biodegradable inner covering or coating has a thickness intentionally selected such that portions of the first or inner covering or coating which overlay first structural elements of the scaffold are intentionally configured to tear, break, rupture, open, and/or become porous (e.g., by way of thinning and/or stretching) in response to or following fracture or breakage of the preferentially fracturable structural elements or links, thereby exposing portions of these fractured or broken structural elements to a physical environment in which the scaffold structure resides, such as a biological environment in which scaffold biodegradation can occur by way of biological fluid / chemical species incursion or biological fluid contact, which can enable gradual or controlled progressive biodegradation of portions of the scaffold beginning at such fractured or broken first structural elements that are exposed to such an environment.
  • a first or inner non-biodegradable inner covering or coating e.g., inner coating 20
  • the first or inner covering or coating has a thickness intentionally selected such that
  • Various embodiments in accordance with the present disclosure thus synergistically utilize preferentially fracturable structural elements or links in combination with the first or inner non-biodegradable inner covering or coating of an appropriate thickness to intentionally modulate or control the exposure or permeability of portions of the base biodegradable scaffold material to biological fluid and/or chemical species incursion and/or contact, e.g., thus providing managed, slow / gradual, or very slow / very gradual intended biodegradation of the scaffold (e.g., including preferential biodegradation of particular portions of the scaffold, such as preferentially fracturable links 140 relative to other portion of the scaffold such as radial support rings 130) relative to or over an intended or target time period (e.g., approximately 4 - 12 weeks or longer).
  • an intended or target time period e.g., approximately 4 - 12 weeks or longer.
  • first or inner non-biodegradable inner covering or coating controls (e.g., intentionally / preferentially controls, in an intended, generally consistent, generally predictable, consistent, or predictable manner) access of chemical species, biological fluids, and/or saline to particular or intended portions of the underlying biodegradable scaffold (e.g., relative to an intended or target time period such as set forth above).
  • At least portions of the first or inner non-biodegradable inner covering or coating can be selected to have an appropriate thickness (e.g., between approximately 0.5 - 3 micrometers, approximately 1 - 3 micrometers, approximately 0.5 - 2.5 micrometers, or approximately 1 - 2.5 micrometers) such that stresses exerted upon remaining or still intact portions of the scaffold structure over a particular period of time (e.g., approximately 4 to 12 weeks or longer post- implantation), including stresses exerted on as-yet unbroken preferentially fracturable structural elements or links and/or substantially intact, essentially intact, or intact portions of at least some ring-like or ring-type structures such as radial support rings 130, progressively, gradually, or very gradually stretch, thin, and/or render porous at least some regions or sites on the first or inner non-biodegradable inner covering or coating that overlay the remaining or still intact portions of the scaffold, thereby exposing or further exposing these portions of the scaffold to biological fluid
  • endothelial tissue can progressively grow around and/or into portions of the scaffold structure (e.g., around and/or into radial support rings 130 or portions thereof that remain significantly covered or covered by the non-biodegradable inner covering or coating), such that non-degradable portions of the scaffold structure (e.g., the inner covering or coating, and the radiopaque material(s)) become physically embedded or incorporated into vessel tissue.
  • portions of the scaffold structure e.g., around and/or into radial support rings 130 or portions thereof that remain significantly covered or covered by the non-biodegradable inner covering or coating
  • such endothelial tissue growth can disrupt the continuity of portions of the first or inner non-biodegradable covering or coating and/or disrupt adherence of portions of the first or inner non-biodegradable covering or coating to the scaffold, thereby enabling further scaffold biodegradation.
  • the inner covering or coating can remain as a thin biocompatible layer within vessel tissue.
  • the outer coating can be non-porous over portions of the scaffold structure corresponding to the radial support rings, but porous over portions of the scaffold structure corresponding to at least some preferentially fracturable links; and/or the scaffold structure can include radiopaque material(s) on top of the inner coating corresponding to the radial support rings, but can exclude radiopaque material(s) on top of the inner coating corresponding to the preferentially fracturable links.

Landscapes

  • Health & Medical Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Surgery (AREA)
  • Epidemiology (AREA)
  • Physics & Mathematics (AREA)
  • Optics & Photonics (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Inorganic Chemistry (AREA)
  • Cardiology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Materials For Medical Uses (AREA)

Abstract

Structure d'échafaudage implantable comprenant un échafaudage métallique biodégradable ; un revêtement polymère non biodégradable interne recouvrant de manière conforme l'échafaudage ; un revêtement externe formé d'un polymère biodégradable ou non biodégradable, et ayant une surface externe ; et un matériau radio-opaque disposé à l'extérieur du revêtement interne et interne à la surface externe du revêtement externe le long de la longueur de la structure d'échafaudage, le revêtement interne isolant électrochimiquement le matériau radio-opaque de l'échafaudage. La structure d'échafaudage comprend une pluralité de bagues de support radiales, chacune comprenant une paire d'entretoises radiales qui sont accouplées axialement par des éléments de pont. Des bagues de support radiales adjacentes par paires sont accouplées axialement par des liaisons de préférence fracturables, chacune comprenant une section incurvée le long de sa longueur qui est mécaniquement plus faible que les entretoises ou les éléments de pont, de telle sorte que des nombres croissants d'éléments de support radiaux adjacents deviennent progressivement découplés les uns des autres au cours du temps après l'implantation de la structure d'échafaudage.
PCT/US2020/036045 2020-06-03 2020-06-04 Échafaudage métallique biodégradable radio-opaque ayant un revêtement non biodégradable, et qui comprend des bagues de support radiales et des liaisons axiales souples de manière résiliente, de préférence fracturables entre ces dernières WO2021247024A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SG10202005249S 2020-06-03
SG10202005249S 2020-06-03

Publications (1)

Publication Number Publication Date
WO2021247024A1 true WO2021247024A1 (fr) 2021-12-09

Family

ID=78830563

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2020/036045 WO2021247024A1 (fr) 2020-06-03 2020-06-04 Échafaudage métallique biodégradable radio-opaque ayant un revêtement non biodégradable, et qui comprend des bagues de support radiales et des liaisons axiales souples de manière résiliente, de préférence fracturables entre ces dernières

Country Status (1)

Country Link
WO (1) WO2021247024A1 (fr)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6174329B1 (en) * 1996-08-22 2001-01-16 Advanced Cardiovascular Systems, Inc. Protective coating for a stent with intermediate radiopaque coating
US8021418B2 (en) * 2003-06-19 2011-09-20 Boston Scientific Scimed, Inc. Sandwiched radiopaque marker on covered stent
US20120065722A1 (en) * 2010-09-15 2012-03-15 Pacetti Stephen D Bioabsorbable Superficial Femoral Stent Patterns With Designed To Break Links
US20170312102A1 (en) * 2012-03-09 2017-11-02 Q3 Medical Devices Limited Biodegradable supporting device

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6174329B1 (en) * 1996-08-22 2001-01-16 Advanced Cardiovascular Systems, Inc. Protective coating for a stent with intermediate radiopaque coating
US8021418B2 (en) * 2003-06-19 2011-09-20 Boston Scientific Scimed, Inc. Sandwiched radiopaque marker on covered stent
US20120065722A1 (en) * 2010-09-15 2012-03-15 Pacetti Stephen D Bioabsorbable Superficial Femoral Stent Patterns With Designed To Break Links
US20170312102A1 (en) * 2012-03-09 2017-11-02 Q3 Medical Devices Limited Biodegradable supporting device

Similar Documents

Publication Publication Date Title
CA2683144C (fr) Stent hybride ayant un squelette de fibre ou de fil
ES2968361T3 (es) Un método para elaborar un implante autoexpandible
US8603155B2 (en) Stent having improved stent design
US20070270940A1 (en) Bioabsorbable Magnesium-Reinforced Polymer Stents
EP2429462B1 (fr) Endoprothèse sensible à l'érosion biologique
US20100004733A1 (en) Implants Including Fractal Structures
US20080200979A1 (en) Anti-restenotic therapeutic device
US10898355B2 (en) Bioresorbable stent
US20110282428A1 (en) Biodegradable composite stent
JP2008541840A (ja) ステントの側枝花弁部の選択的な処理
WO2006031284A2 (fr) Endoprothese couverte avec diffusion regulee d'agent therapeutique
JP6667758B2 (ja) 生体吸収性ステント
CN104870028A (zh) 完全可吸收的管腔内设备及其制造方法
WO2018137763A1 (fr) Dispositif endoluminal
US20140144001A1 (en) Stent having function elements
AU2013338009B2 (en) Devices and methods related to deposited support structures
WO2021247024A1 (fr) Échafaudage métallique biodégradable radio-opaque ayant un revêtement non biodégradable, et qui comprend des bagues de support radiales et des liaisons axiales souples de manière résiliente, de préférence fracturables entre ces dernières
US10201639B2 (en) Drug-eluting medical implants
US10959715B2 (en) Devices and methods related to deposited support structures
Wnek et al. Stents/Benjamin Thierry, Luc Bilodeau, Maryam Tabrizian

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 20939134

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 20939134

Country of ref document: EP

Kind code of ref document: A1