WO2020061176A1 - Dispositifs implantables - Google Patents

Dispositifs implantables Download PDF

Info

Publication number
WO2020061176A1
WO2020061176A1 PCT/US2019/051704 US2019051704W WO2020061176A1 WO 2020061176 A1 WO2020061176 A1 WO 2020061176A1 US 2019051704 W US2019051704 W US 2019051704W WO 2020061176 A1 WO2020061176 A1 WO 2020061176A1
Authority
WO
WIPO (PCT)
Prior art keywords
thermoplastic polymer
polymer matrix
implantable device
reinforcement
poly
Prior art date
Application number
PCT/US2019/051704
Other languages
English (en)
Inventor
Ryan ROEDER
Gabriel L. Converse
Stephen M. Smith
Original Assignee
Happe Spine Llc
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
Priority claimed from US16/134,453 external-priority patent/US11179243B2/en
Application filed by Happe Spine Llc filed Critical Happe Spine Llc
Publication of WO2020061176A1 publication Critical patent/WO2020061176A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/44—Joints for the spine, e.g. vertebrae, spinal discs
    • A61F2/4455—Joints for the spine, e.g. vertebrae, spinal discs for the fusion of spinal bodies, e.g. intervertebral fusion of adjacent spinal bodies, e.g. fusion cages
    • 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
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/44—Joints for the spine, e.g. vertebrae, spinal discs
    • A61F2/4455—Joints for the spine, e.g. vertebrae, spinal discs for the fusion of spinal bodies, e.g. intervertebral fusion of adjacent spinal bodies, e.g. fusion cages
    • A61F2/446—Joints for the spine, e.g. vertebrae, spinal discs for the fusion of spinal bodies, e.g. intervertebral fusion of adjacent spinal bodies, e.g. fusion cages having a circular or elliptical cross-section substantially parallel to the axis of the spine, e.g. cylinders or frustocones
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A61L27/46—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with phosphorus-containing inorganic fillers
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56—Porous materials, e.g. foams or sponges
    • 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
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/30767—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
    • A61F2002/3092—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth having an open-celled or open-pored structure
    • 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
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/30767—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
    • A61F2002/3093—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth for promoting ingrowth of bone tissue
    • 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
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/44—Joints for the spine, e.g. vertebrae, spinal discs
    • A61F2002/4495—Joints for the spine, e.g. vertebrae, spinal discs having a fabric structure, e.g. made from wires or fibres
    • 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/38—Materials or treatment for tissue regeneration for reconstruction of the spine, vertebrae or intervertebral discs

Definitions

  • the present disclosure relates generally to composite biomaterials and more particularly to porous composite biomaterials and related methods.
  • Natural bone grafts such as autogenous bone grafts (autografts) are commonly used in procedures for repairing or replacing bone defects because they provide good structural support and osteoinductivity. Natural bone grafts involve removing or harvesting tissue from another part of a host’s body (e.g., typically from the iliac crest, hip, ribs, etc.) and implanting the harvested tissue in the defect site. Not only do these grafts require an added surgical procedure needed to harvest the bone tissue, these grafts have limitations, including for example, transplant site morbidity.
  • allografts involve removing and transplanting tissue from another human (e.g., from bone banks that harvest bone tissue from cadavers) to the defect site.
  • allografts are known to induce infection and immunotoxicity, suffer from limited supply and variability, and have a lessened effectiveness because the cells and proteins that promote bone growth are lost during the harvesting process (e.g., during cleansing and disinfecting process).
  • Demineralized bone matrix (DBM) is typically used to induce bone growth at defect sites, but DBM lacks the mechanical properties (e.g., stiffness, strength, toughness, etc.) necessary to be considered a viable option for load-bearing applications.
  • Synthetic bone substitute materials have been researched in the treatment of diseased bone (e.g., osteoporosis), injured bone (e.g., fractures), or other bone defects in lieu of natural bone grafts.
  • Synthetic bone substitutes are viable alternatives to the more traditional methods described above.
  • synthetic substitute materials used to repair diseased bones and joints should function or perform biologically and mechanically (i.e., as the structural support role of the bone itself) by, for example, mimicking the density and overall physical structure of natural bone to provide a framework for ingrowth of new tissue.
  • One type or application of a synthetic bone substitute is a scaffold, which provides support for bone-producing cells.
  • Scaffolds may be biodegradable, which degrade in vivo, or they may be non-biodegradable to provide permanent implant fixation (e.g., spinal fusion cages).
  • scaffolds are typically biocompatible, and some may be bioactive, bioresorbable, osteoconductive, and/or osteoinductive. The shapability, deliverability, cost, and ability to match the mechanical properties of the surrounding host tissue are other factors that vary among different types of scaffolds and other bone substitutes.
  • FIG. 1A is a perspective view of an example porous composite material described herein.
  • FIG. 1B is a cross-sectional view of a portion of the example porous composite material of FIG. 1A.
  • FIG. 2A, 2B and 2C are scanning electron micrographs of a portion of the example porous composite material shown in increasing magnification.
  • FIGS. 3 is graphical representation of the elastic modulus of example apatite reinforced polymer composites versus the reinforcement volume fraction.
  • FIG. 4 shows scanning electron micrograph of a portion of the surface of an example composite material reinforced with calcium phosphate whiskers embedded within and exposed on the surface, and schematically showing the orientation of the whiskers relative to the loading direction of the material or scaffold strut.
  • FIG. 5 A is a schematic illustration of a known spinal fusion cage inserted between spinal vertebrae.
  • FIG. 5B illustrates the example known spinal fusion cage of FIG. 5 A.
  • FIG. 6 illustrates another example of an implant comprising a scaffold described herein.
  • FIG. 7 illustrates yet another example of an implant comprising a scaffold described herein.
  • FIG. 8 is a flow diagram illustrating an example process of creating an example composite material apparatus described herein.
  • the example methods, apparatus, and materials described herein provide a biocompatible, bioactive synthetic porous composite for use as synthetic bone substitute materials.
  • the synthetic composite may provide a synthetic porous scaffold for use in an orthopedic implant and/or be injectable via percutaneous or surgical injection to cure in vivo. Because the example composite material is used to form a scaffold or matrix that is used in an implantable device, the descriptions of one or more of these structures may also describe one or more of the other structures.
  • the synthetic porous composites are tailored to mimic biological and mechanical properties of bone tissue for implant fixation, synthetic bone graft substitutes, tissue engineering scaffolds, interbody spinal fusion, or other orthopedic applications.
  • An example porous composite material described herein reduces subsidence and/or bone resorption resulting from mechanical mismatch problems between a synthetic scaffold of an implant device and the peri-implant tissue. Additionally, porosity and/or the pore sizes of the example synthetic composite are tailorable to specific applications to effectively promote the vascularization and growth of bone in the pores and/or void spaces of the example scaffolds, thereby improving bonding between the scaffolds and peri-implant tissue.
  • the example composite material or scaffolds are synthesized or made through a process that enables reinforcement particles to be integrally formed with or embedded within polymer matrices. In this manner, the polymer matrices embedded with the reinforcement material provide improved material properties (e.g., stiffness, fatigue strength, and toughness).
  • the reinforcement particles are also exposed on a surface of the matrices, which promotes bioactivity and/or bioresorption. Additionally, the process provides flexibility to tailor the level of reinforcement particles and porosity for a desired application. For example, a porogen material may be used to vary the porosity, while the pore size is tailored by, for example, sieving the porogen to a desired size.
  • the mechanical properties (e.g., stiffness, strength, toughness, etc.) of the example scaffold of the implant device may be tailored to match those of the adjacent peri-implant bone tissue to reduce mechanical mismatch problems. Reducing mechanical mismatch provides a decreased risk of subsidence, stress shielding, bone resorption, and/or subsequent failure of adjacent peri-implant bone tissue. Additionally, the example scaffold of the implant device may include a significantly high porosity to promote bone ingrowth, while exhibiting significantly higher effective mechanical properties such as, for example, the mechanical properties of trabecular bone.
  • the example composite material includes a continuous porous biocompatible matrix having a thermoplastic polymer matrix reinforced with anisometric calcium phosphate particles.
  • a composite material includes a polyetheretherketone (PEEK) or a polyetherketoneketone (PEKK) matrix reinforced with various volume fractions of hydroxyapatite (HA) whiskers (e.g., 20 or 40 volume percent), wherein the matrix is approximately between and including 1% and 95%, and in some embodiments between and including 40% and 90%, and in some particular embodiments between and including 70% and 90% porous.
  • PEEK polyetheretherketone
  • PEKK polyetherketoneketone
  • HA hydroxyapatite
  • the porous matrix includes a biocompatible, microporous polymer cage reinforced with anisometric calcium phosphate particles and bone morphogenic protein (BMP) such as, for example, rhBMP-2, which can be dispersed or accommodated by the void spaces and/or pores of the example porous scaffold and/or exposed on the surface of the example porous scaffold. Additionally, the BMP binds to the calcium phosphate further localizing the BMP to the surface of the scaffold or matrix.
  • BMP bone morphogenic protein
  • the example composite materials described herein may be used for applications such as, for example, synthetic bone graft substitutes, bone ingrowth surfaces applied to existing implants, tissue engineering scaffolds, interbody spinal fusion cages, etc.
  • carrier materials e.g., collagen, hydrogels, etc.
  • growth factors such as BMP
  • Human bone tissues exhibit substantial variation in mechanical properties depending on the tissue density and microstructure. The properties are highly dependent on anatomic location and apparent density of the measured specimen.
  • a femur includes a cortical bone that has a relative porosity on the order of about 5-15%, and a trabecular bone that has a porosity on the order of about 75-95%. Due to the highly significant porosity differences, the trabecular bone exhibits significantly lower effective mechanical properties compared to the cortical bone. Therefore, depending on the application, synthetic composite materials for use as scaffolds and/or spinal fusion cages or other implant devices should possess the mechanical properties exhibited by the cortical bone or the trabecular bone, but must also have effective porosity to promote bone growth.
  • the example scaffold of the implant device described herein may be tailored to substantially match or mimic the mechanical properties (e.g., stiffness, strength, toughness, etc.) of the adjacent and/or substituted bone tissue.
  • the mechanical properties e.g., stiffness, strength, toughness, etc.
  • Several factors may be varied during the synthesis of the composite material and scaffold of the implant device to tailor the mechanical properties including the calcium phosphate reinforcement volume fraction, aspect ratio, size and orientation; the polymer; and the size, volume fraction, shape and directionality of the void space and/or porosity. Tailoring the mechanical properties of the scaffold reduces the likelihood of mechanical mismatch leading to a decreased risk of subsidence, stress shielding, bone resorption and/or subsequent failure of adjacent vertebrae.
  • FIG. 1A illustrates the example synthetic porous composite material 100 described herein.
  • FIG. 1B is a cross-sectional view of a portion of the example porous composite material 100 of FIG. 1A.
  • the example synthetic composite material 100 provides a synthetic porous scaffold 101 for use or in as an orthopedic implant.
  • the example synthetic porous composite material 100 includes a porous thermoplastic polymer (e.g., a PEEK polymer) matrix 102 having anisometric calcium phosphate reinforcement particles 104 integrally formed or embedded with the matrix 102 and/or exposed on a surface of the matrix 102.
  • a porous thermoplastic polymer e.g., a PEEK polymer
  • the porous polymer matrix 102 includes a substantially continuous porosity and a plurality of pores 106 to enable bone ingrowth into the porous matrix 102.
  • the matrix 102 is substantially continuously interconnected via a plurality of struts 108.
  • at least one of the plurality of struts 108 may be a load-bearing strut.
  • FIGS. 2A-2C are scanning electron micrographs showing increasing magnification of a portion of an example scaffold 200 with struts 202.
  • the example scaffold 200 is a PEEK scaffold reinforced with 40% by volume E1A whiskers 204.
  • FIG. 2A illustrates the architecture or matrix 206 of the scaffold 200 and FIG. 2B illustrates an enlarged portion of the struts 202.
  • the HA whiskers 204 are integrally formed and/or embedded within the matrix 206 of the scaffold 200 for reinforcement.
  • the HA whiskers 204 are also exposed on a surface 208 of the matrix of the scaffold 200 for bioactivity and/or bioresorption, as noted above.
  • the HA whiskers 204 are aligned in a sheet texture and are exposed on the surface 208 of the struts 202.
  • the thermoplastic polymer of the example scaffolds described herein may be a biodegradable polymer for synthetic bone graft substitute applications, or nonbiodegradable for implant fixation applications.
  • the thermoplastic polymer includes a continuous matrix of a composite material and is biocompatible and/or bioresorbable as described above. Additionally, or alternatively, the polymer may be a radiolucent polymer, bioresorbable (i.e., a material capable of being resorbed by a patient under normal physiological conditions) and/or non- bioresorbable, as desired.
  • the thermoplastic polymer matrix may include a polymer suitable for injection via percutaneous or surgical injection so that the composite material 100 cures in vivo.
  • Suitable non-resorbable polymers include, without limitation, polyaryletherketone (PAEK), polyetheretherketone (PEEK), polyetherketonekteone (PEKK), polyetherketone (PEK), polyethylene, high density polyethylene (HDPE), ultra-high molecular weight polyethylene (UHMWPE), low density polyethylene (LDPE), polyethylene oxide (PEO), polyurethane, polypropylene, polypropylene oxide (PPO), polysulfone, polypropylene, copolymers thereof, and blends thereof.
  • PAEK polyaryletherketone
  • PEEK polyetheretherketone
  • PEKK polyetherketonekteone
  • PEK polyetherketone
  • PEK polyethylene, high density polyethylene (HDPE), ultra-high molecular weight polyethylene (UHMWPE), low density polyethylene (LDPE), polyethylene oxide (PEO), polyurethane, polypropylene, polypropylene oxide (PPO), polysulfone, polypropylene, copolymers thereof
  • Suitable bioresorbable polymers include, without limitation, poly(DL-lactide) (PDLA), poly(L-lactide) (PLLA), poly(glycolide) (PGA), poly( -caprolactone) (PCL), poly(dioxanone) (PDO), poly(glyconate), poly(hydroxybutyrate) (PHB), poly(hydroxyvalerate (PHV), poly(orthoesters), poly(carboxylates), polypropylene fumarate), poly(phosphates), poly(carbonates), poly(anhydrides), poly(iminocarbonates), poly(phosphazenes), copolymers thereof, and blends thereof.
  • PDLA poly(DL-lactide)
  • PLA poly(L-lactide)
  • PGA poly(glycolide)
  • PCL poly( -caprolactone)
  • PDO poly(dioxanone)
  • PDO poly(glyconate), poly(hydroxybutyrate) (PHB), poly
  • Suitable polymers that are injectable via percutaneous or surgical injection that cure in vivo include, without limitation, polymethylmethacrylate (PMMA), and other polyacrylics from monomers such as bisphenol a hydroxypropylmethacrylate (bis-GMA) and/or tri(ethylene glycol) dimethacrylate (TEG-DMA).
  • PMMA polymethylmethacrylate
  • bis-GMA bisphenol a hydroxypropylmethacrylate
  • TEG-DMA tri(ethylene glycol) dimethacrylate
  • the polymers are reinforced.
  • the reinforcement particles 104 described above may be, for example, calcium phosphate.
  • the reinforced composite material may comprise other reinforcement particles, for instance particles that are other than calcium phosphate.
  • the reinforcement particles may be other than anisometric.
  • the reinforcement particles may comprise a blend of different particles that vary in terms of composition, size, and shape.
  • the aspect ratio, size, volume fraction and degree of preferred orientation of the calcium phosphate particles 104 may be tailored for the desired material properties and implant performance.
  • FIG. 3 is a graphical illustration of the elastic modulus of HA whisker and powder reinforced polymer composite materials versus the volume fraction percentage of the apatite calcium phosphates that is mixed with the polymer matrix.
  • the shaded areas of FIG. 3 show approximate regions for the given mechanical property of the human cortical bone tissue.
  • the elastic modulus of the composite materials increases with increasing HA content.
  • increasing the level of HA reinforcement in polymer composites increases cellular activity during osteointegration.
  • the calcium phosphate reinforcement particles 104 may be in the form of single crystals or dense polycrystals but are at least in some portion anisometric.“Anisometric” refers to any particle morphology (shape) that is not equiaxed (e.g., spherical), such as whiskers, plates, fibers, etc. Anisometric particles are usually characterized by an aspect ratio. For example, HA single crystals are characterized by the ratio of dimensions in the c- and a-axes of the hexagonal crystal structure. Thus, the anisometric particles in the present disclosure have an aspect ratio greater than 1. In one example, the mean aspect ratio of the reinforcement particles is from greater than 1 to about 100.
  • the mean aspect ranges from greater than 1, to 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47,
  • the reinforcement particles can be provided in an amount of from about 1% by volume of the composite biomaterial to about 60% by volume, based on the volume of the thermoplastic polymer matrix, and for example, from about 20% by volume to about 50% by volume.
  • the volume of reinforcement particles present in the thermoplastic polymer matrix can range from about 1% to about 60%, from about 5% to about 55%, from about 10 to about 50%, from about 15 to about 45%, from about 15 to about 30%, from about 20 to about 40%, from about 25 to about 35%, and any suitable combination, sub-combination, range, or sub-range thereof by volume, based on the volume of the thermoplastic polymer matrix.
  • the reinforcement particles may be present, by volume, based on the total volume of the thermoplastic polymer matrix, from about 1, 2, 3, 4, 5, 6, 7, 8, 9,
  • the calcium phosphate reinforcements particles 104 may be oriented in bulk or near the surface of the polymer matrix 102 to provide directional properties, if desired. For example, if the reinforcement particles 104 are predominately aligned within the matrix 102 the morphological alignment of the particles 104 provides anisotropy for the overall composite 100, which can be tailored to be similar to the anisotropic mechanical properties of bone tissues.
  • FIG. 4 shows a micrograph of anisometric calcium phosphate reinforcement 400 on the surface of a dense composite polymer matrix 402. Also shown in FIG.
  • FIG. 4 is a schematic illustration of a portion of matrix 402 and illustratively showing the orientation of the reinforcement particles 400 relative to the loading direction of the material and/or a scaffold strut, which is, for example, at an angle 0.
  • the size or amount of the calcium phosphate particles 104 in matrix 102 there are no limits on the size or amount of the calcium phosphate particles 104 in matrix 102, provided that the calcium phosphate particles 104 are dispersed within and/or exposed at the surface of the polymer matrix 102.
  • the reinforcement particles 104 may have a maximum dimension from about 20 nm to about 2 mm, and for example, between and including 20 nm to about 100 pm.
  • nano-scale calcium phosphate particles improve the mechanical properties of the example synthetic composite material 100 described herein, nano-scale calcium phosphate particles are particularly effective for enhancing bioresorbability and cell attachment, and micro-scale particles are particularly effective for obtaining a uniform dispersion within the matrix 102.
  • the reinforcement particles may have a size from about 20 nm to about 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900 nm, and to about 1 pm to about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900 pm, and to about 1 mm and up to and including 2mm, including increments and ranges therein and there between.
  • Suitable calcium phosphates may include, without limitation, calcium HA, HA whiskers, HA, carbonated calcium HA, beta-tricalcium phosphate (beta-TCP), alpha-tricalcium phosphate (alpha-TCP), amorphous calcium phosphate (ACP), octacalcium phosphate (OCP), tetracalcium phosphate, biphasic calcium phosphate (BCP), anhydrous dicalcium phosphate (DCPA), dicalcium phosphate dihydrate (DCPD), anhydrous monocalcium phosphate (MCPA), monocalcium phosphate monohydrate (MCPM), and combinations thereof.
  • the calcium phosphate could include calcium HA, carbonated calcium HA, or beta-tricalcium phosphate (beta-TCP), etc.
  • a synthetic composite material 100 not only bears physiological levels of load, but also promotes oseteointegration - the direct structural and functional connection between the living bone and the surface of the load-bearing implant.
  • the bioactive calcium phosphate particles 104 e.g., HA whiskers exposed on the surface of the example porous matrix 102 promote a stable bone-implant interface. Osteointegration also requires the vascularization and growth of bone into an implant via interconnected and/or continuous porosity.
  • the size, volume fraction, shape, and directionality of the void spaces and/or pores 106 may be tailored to optimize osteoconduction and implant mechanical properties.
  • the pores 106 may be any size or shape, while maintaining a continuous network to promote a fusion through the formation of new bone tissue in the void spaces and/or pores 106.
  • the pores 106 may be present throughout the matrix 102 as illustrated in FIG. 1A.
  • the pores 106 may be functionally graded in any material or implant direction, for example radially as shown in FIGS. 6 and 7, from a highly porous region to a relatively dense region or may include a void space.
  • the change in porosity from one region to another may be very distinct, for example as shown in FIGS. 6 and 7, or gradual.
  • the graded change may be uniform or variant.
  • the central void may be any shape or size, and may receive (e.g., be filled) a material, a structure, or the composite material 100 (i.e., the composite material graded from the porous outer surface to a dense center), thereby forming a porous outer perimeter and a dense central region. Examples are further described in connection with FIGS. 6 and 7 below.
  • the term“void” as used in connection with a feature of an implant, for example as shown in FIG 5B, formed with the porous scaffold refers to a cavity or hole that is other than a pore.
  • the porosity and/or pore sizes 106 may be selectively formed by the inclusion of, for example, a porogen material during synthesis of the composite material 100. Pores sizes may range from about 100 pm to about 500 pm, and, for example, from about 250 pm to about 500 pm.
  • the example composite biomaterial 100 may additionally contain some fraction of microporosity within scaffold struts that is less than about 10 pm in size.
  • pores present in the thermoplastic polymer matrix can each have a size that ranges from about 10 pm to about 500 pm, including from about 10 pm to about 100 pm, from about 25 to about 85 pm, from about 40 pm to about 65 pm, and from about 100 pm to about 500 pm, from about 150 pm to about 450 pm, from about 200 pm to about 400 pm, from about 250 pm to about 350 pm, and any suitable combination, sub-combination, range, or sub-range thereof.
  • thermoplastic polymer matrix includes pores having sizes that are different, wherein at least a portion of the pores has a different size than other pores, each pore having a different size within the range from about from about 10 pm to about 500 pm.
  • the pores may have a size from about 1, 2, 3, 4, 5, 6,
  • the total amount of porosity within porous regions may range up to 95%, including from about 1% to about 90% by volume, and, for example, between and including about 70% to 90% by volume.
  • the extent of porosity in the porous reinforced composite scaffold can range from about 1% to about 95%, from about 5% to about 90%, from about 10 to about 85%, from about 15 to about 80% from about 20 to about 75%, from about 25 to about 70%, from about 30 to about 65%, from about 35 to about 60%, from about 40 to about 55%, from about 45 to about 50%, and any suitable combination, sub- combination, range, or sub-range thereof by volume, based on the volume of the porous reinforced composite scaffold.
  • the extent of pores, by volume, based on the total volume of the porous reinforced composite scaffold can be from about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
  • the porosity may also be tailored via other processes such as, for example, microsphere sintering, fiber weaving, solvent casting, electrospinning, freeze drying (lyophilization), thermally induced phase separation, gas foaming, and rapid prototyping processes such as solid freeform fabrication, robotic deposition (aka, robocasting), selective laser sintering, fused deposition modeling, three-dimensional printing, laminated object manufacturing, stereolithography, etc., or any other suitable process(es) or combination(s) thereof.
  • processes such as, for example, microsphere sintering, fiber weaving, solvent casting, electrospinning, freeze drying (lyophilization), thermally induced phase separation, gas foaming, and rapid prototyping processes such as solid freeform fabrication, robotic deposition (aka, robocasting), selective laser sintering, fused deposition modeling, three-dimensional printing, laminated object manufacturing, stereolithography, etc., or any other suitable process(es) or combination(s) thereof.
  • the example composite material 100 may optionally include additives, if desired.
  • the composite material 100 may include one or more surface-active agents to enhance interfacial bonding between the reinforcement particles 104 and the polymer matrix 102.
  • the void spaces and/or pores 106 may accommodate and deliver one or more growth factors such as, for example, BMP, to enhance osteoinductivity and/or bone regeneration.
  • the void spaces and/or pores 106 may also accommodate and deliver one or more transcription factors, matrix metalloproteinases, peptides, proteins, bone cells, progenitor cells, blood plasma, bone marrow aspirate, or combinations thereof, to improve or speed bone regeneration, or resorption and replacement of the biomaterial.
  • the void spaces and/or pores 106 may further accommodate a carrier material that may be incorporated into the void spaces and/or pores 106.
  • the carrier material may include, for example, a collagen sponge, membrane, or a hydrogel material to deliver the growth factor material such as, for example, the BMP.
  • FIG. 5A is an illustration showing a known interbody spinal fusion cage 500.
  • the example spinal fusion cage 500 is implanted in the inter-vertebral space 502 between two adjacent vertebrae 506 and 508.
  • a disc 510 due to degeneration, herniation, etc., is typically removed and replaced by the spinal fusion cage 500.
  • the spinal fusion cage 500 is used to support or restore vertebral height, and, thus, stabilize or retain adjacent vertebrae 506 and 508 in a desired position. Additionally, the spinal fusion cage 500 is to promote fusion between the vertebrae 506 and 508.
  • FIG. 5B is an enlarged illustration of the known spinal fusion cage 500 of FIG. 5A.
  • a typical spinal fusion cage 500 includes a body 510 having a dense outer region 512 and a void 514 at its center.
  • the dense outer surface 512 may be made of PEEK, titanium, or other material that can be used to support the vertebrae 506 and 508.
  • the spinal fusion cage 500 made of a PEEK, titanium, etc. cannot attach to the bone.
  • the center void 514 is typically provided with a packing material (not shown) such as, a natural bone graft, a collagen sponge that retains bone growth factors, or the spinal fusion cage 500 is coated with the bone growth factors or other agents that promote osteoinduction.
  • the example porous scaffold 101 having the composite material 100 described herein, and with respect to FIG. 1A, can be implemented with the spinal fusion cage 500 of FIGS. 5 A and 5B to replace the packing materials, such as natural bone graft.
  • the porous scaffold 101 promotes bone ingrowth and the pores 106 may accommodate or deliver for example, a BMP, to further improve rate of growth (fusion rate).
  • the calcium phosphate e.g., HA whisker
  • FIG. 6 illustrates another example scaffold or matrix 600 implemented with the example composite material 100 described herein.
  • the example scaffold 600 may be implemented as an interbody spinal fusion cage.
  • the scaffold 600 includes a body 602 having a porous polymer matrix 604 integrally formed or embedded with anisometric calcium phosphate particles 606.
  • the matrix 604 of the example scaffold 600 includes a radiolucent polymer (e.g., PEEK) integrally formed or embedded with anisometric calcium phosphate reinforcements 606 such as, for example, HA whiskers.
  • the radiolucent polymer provides improved radiographic analysis of fusion following implantation.
  • the example scaffold 600 may also include a BMP such as, for example, rhBMP-2.
  • the example scaffold 600 is a biocompatible, microporous polymer scaffold or matrix supplemented with anisometric calcium phosphate reinforcements and BMP.
  • the example scaffold 600 may be formed so that the pores are functionally graded in any material or implant direction, for example radially as shown in FIG. 6, from a highly porous center or central region 608 to relatively dense outer region or surface 610.
  • the change in porosity from one region to another may be very distinct or gradual from the central region 608 to the outer region 610. Further, the graded change may be uniform or variant.
  • the dense outer region 610 provides structural integrity along with the advantages of the composite material 100 described herein.
  • the porous structure 604 has pore sizes that range between and including about 100 pm and about 500 pm, and in some embodiments, between and including about 250 pm and about 500 pm, and a porosity that ranges approximately between and including 1% and 95%, and in some embodiments between and including 40% and 90%, and in some particular embodiments between and including 70% and 90% porous.
  • the spinal fusion cage material 600 may include microporosity having pore sizes less than about 10 pm.
  • FIG. 7 illustrates another example scaffold 700.
  • the porous scaffold 700 includes a porous matrix 702 having the composite material 100 described herein.
  • the porous scaffold 700 includes a center or central void 704 that may be any shape or size. Additionally, or alternatively, the central void 704 may receive a material 706, a stem, or any other substance or structure, illustratively depicted by dashed lines.
  • the central void 704 may receive a stem 706 (e.g., an implant) such as, for example, a titanium stem, a dense composite stem (e.g., a PEEK composite stem), or any other suitable material or structure.
  • a stem 706 e.g., an implant
  • a dense composite stem e.g., a PEEK composite stem
  • the scaffold 700 is formed so that the pores are functionally graded in any material or implant direction, for example radially as shown in FIG. 7, from a from the high porous outer region or surface 702 to a relatively dense center or central region 708.
  • the change in porosity from one region to another may be very distinct or gradual from the central region 708 to the highly porous outer region 702. Further, the graded change may be uniform or variant.
  • the example scaffold 700 forms a porous perimeter having a dense core, where the material is continuous from the porous perimeter to the dense core.
  • the dense central region 708 provides structural integrity along with the advantages of the composite material 100 described herein.
  • the porous matrix 702 and the dense central region 708 may have pore sizes that range between and including about 100 pm and about 500 pm, and in some embodiments, between and including about 250 pm and about 500 pm, and a porosity that ranges approximately between and including 1% and 95%, and in some embodiments between and including 40% and 90%, and in some particular embodiments between and including 70% and 90% porous, and including within any of the ranges as described herein above.
  • the spinal fusion cage 700 may include a microporosity having pore sizes less than about 10 pm and including within any of the ranges as described herein above.
  • the composite material 100 and/or the scaffolds 101, 600, 700 may also include a roughened surface such as, for example, serrated teeth, that come into direct contact with the adjacent peri-implant tissue to prevent movement relative to the peri-implant tissue after implantation.
  • the scaffolds 101, 600, 700 may include holes, notches, pins, radiographic markers, or other features that may be gripped or otherwise used for positioning of the implants comprising the scaffolds 101, 600, 700 by minimally invasive surgical tools and procedures.
  • the example composite material 100 and/or the scaffolds 101, 600, 700 may be manufactured by methods common to reinforced thermoplastic and thermosetting polymers, including but not limited to injection molding, reaction injection molding, compression molding, transfer molding, extrusion, blow molding, pultrusion, casting/potting, solvent casting, microsphere sintering, fiber weaving, solvent casting, electrospinning, freeze drying (lyophilization), thermally induced phase separation, gas foaming, and rapid prototyping processes such as solid freeform fabrication, robotic deposition (aka, robocasting), selective laser sintering, fused deposition modeling, three-dimensional printing, laminated object manufacturing, stereolithography, etc., or any other suitable process(es) or combination(s) thereof.
  • methods common to reinforced thermoplastic and thermosetting polymers including but not limited to injection molding, reaction injection molding, compression molding, transfer molding, extrusion, blow molding, pultrusion, casting/potting, solvent casting, microsphere sintering, fiber weaving, solvent casting, electrospinning, freeze drying (lyophilization), thermally induced
  • FIG. 8 is a flowchart of an example method 800 that may be used to synthesize the example composite material 100 and/or scaffolds 101, 600, 700 described herein. While an example manner of synthesizing the example composite material 100 and/or scaffolds 101, 600, 700 has been illustrated in FIG. 8, one or more of the steps and/or processes illustrated in FIG. 8 may be combined, divided, re-arranged, omitted, eliminated and/or implemented in any other way. Further still, the example method of FIG. 8 may include one or more processes and/or steps in addition to, or instead of, those illustrated in FIG. 8, and/or may include more than one of any or all of the illustrated processes and/or steps. Further, although the example method is described with reference to the flow chart illustrated in FIG. 8, persons of ordinary skill in the art will readily appreciate that many other methods of synthesizing the example composite material 100 and/or scaffolds 101, 600, 700 may alternatively be used.
  • the composite material 100 and/or the scaffolds 101, 600, 700 are processed using a powder processing approach in conjunction with compression molding and particle leaching techniques and is particularly suited for achieving a high concentration (e.g., >40 vol%) of well- dispersed (and aligned, if desired) anisometric calcium phosphate reinforcements (e.g., HA whiskers) in a thermoplastic matrix (e.g., PEEK) with minimal degradation of the calcium phosphate size/shape during processing.
  • a high concentration e.g., >40 vol%
  • anisometric calcium phosphate reinforcements e.g., HA whiskers
  • a thermoplastic matrix e.g., PEEK
  • the calcium phosphate reinforcement volume fraction, aspect ratio, size and orientation; the polymer; and the size, volume fraction, shape and directionality of the void space and/or porosity may be tailored to vary the mechanical properties of the composite material 100 and/or scaffolds 101, 600, 700.
  • a polymer such as, for example, PEEK, and anisometric calcium phosphate particles, such as HA whiskers, are provide in powder form (block 802).
  • the PEEK polymer powder may have, for example, a mean particle size of about 26 pm.
  • the HA whiskers may be synthesized (block 801) using, for example, the chelate decomposition method.
  • the PEEK powder and the synthesized HA whiskers are co-dispersed in a fluid (block 804) such as, for example ethanol, and mixed (block 804) using, for example, ultrasonication under constant stirring - forming a viscous suspension.
  • a fluid such as, for example ethanol
  • the porosity of the mixture is selectively varied and/or tailored (block 806).
  • the porosity may be formed and tailored by the addition of a suitable porogen material such as, for example, NaCl, wax, polysaccharides (sugars), cellulose, etc.
  • the extent of the porosity can be controlled by varying the amount of porogen used (block 805), while the pore size could be tailored by sieving the porogen (block 807) to a desired size prior to mixing the porogen with the polymer mixture.
  • the porosity and/or the pore size of the polymer matrix may be selectively varied using any other suitable methods and/or process(es) such as, for example, microsphere sintering, fiber weaving, solvent casting, electrospinning, freeze drying (lyophilization), thermally induced phase separation, gas foaming, and rapid prototyping processes such as solid freeform fabrication, robotic deposition (aka, robocasting), selective laser sintering, fused deposition modeling, three-dimensional printing, laminated object manufacturing, stereolithography, etc., or any other suitable process(es) or combination(s) thereof.
  • the viscous suspension is wet-consolidated (block 808) by, for example, vacuum filtration and drying to remove any residual fluid (i.e., ethanol).
  • the composite mixture is densified (block 810) by, for example, uniaxial compression, to form a composite preform.
  • the preform is compression molded (block 812) and/or sintered at elevated temperatures (e.g., approximately 20°C to 400°C) sufficient to fuse the polymer particles with minimal damage to the calcium phosphate reinforcements.
  • the process or composite material may be heated to a desired processing temperature and the implant may be shaped or formed (block 814). Densifying and molding the composite material includes aligning the calcium phosphate reinforcement particles (e.g., HA whiskers) morphologically and/or crystallographically within the scaffold struts.
  • the temperature for molding is in the range (°C) from and including 20 to about 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390 to 400 °C including increments and ranges therein and there between.
  • the examples are examples of increments and ranges therein and there between.
  • the scaffold may have any shape and/or size (e.g., any polygonal shape) and can be formed by methods common to reinforced thermoplastic and thermosetting polymers, including but not limited to injection molding, reaction injection molding, compression molding, transfer molding, extrusion, blow molding, pultrusion, casting/potting, solvent casting, and rapid prototyping processes such as solid freeform fabrication, robotic deposition (aka, robocasting), selective laser sintering, fused deposition modeling, three-dimensional printing, laminated object manufacturing, stereolithography, etc., or any other suitable process(es).
  • the composite material 100 and/or the scaffolds 101, 600, 700, are formed by the mold walls and/or machining after molding.
  • the composite material undergoes a leaching process (block 816) to remove, for example, the porogen used during synthesis of the composite material.
  • the leaching may occur, for example, via a dissolution method, heating method, and/or any other suitable methods and/or process(es). More specifically, dissolution may include immersing the scaffold in a fluid, such as, for example, deionized water.
  • viscous flow of the polymer/reinforcement mixture during molding can be designed to tailor the preferred orientation of the anisometric reinforcements in the implant.
  • surface-active agents may be added during the mixing process and/or to the surface of the composite material to enhance interfacial bonding between reinforcement particles and the matrix.
  • HA whiskers were synthesized using the chelate decomposition method. The as-synthesized HA whiskers were measured by optical microscopy to have a mean length of 21.6 pm, width of 2.8 pm and aspect ratio of 7.6.
  • composite scaffolds with 75, 82.5 and 90% porosity were processed with 0-40 vol% HA whisker reinforcement.
  • Appropriate amounts of polymer powder and HA whiskers were co-dispersed in ethanol via a sonic dismembrator and mechanical stirring at 1200 rpm.
  • the appropriate amount of the NaCl i.e., porogen
  • the total scaffold volume consisted of the material volume plus the pore volume.
  • the reinforcement level was calculated based the desired material volume, while the porosity level was calculated based on the total scaffold volume.
  • the viscous suspension was wet-consolidated using vacuum filtration.
  • the powder mixture was dried overnight in a forced convection oven at 90°C and densified at 125 MPa in a cylindrical pellet die using a hydraulic platen press.
  • the die and densified powder mixture was heated in a vacuum oven to the desired processing temperature and transferred to a hydraulic platen press for compression molding. Scaffolds with 82.5 and 90% porosity were molded at 350°C, while scaffolds with 75% porosity were molded at 350, 365 and 375°C.
  • a pressure of 250 MPa was applied to the die as the polymer solidified.
  • the sintered composite pellet was ejected from the die and placed approximately 300 mL deionized water for at least 72 h to dissolve the NaCl crystals. The deionized water was changed daily.
  • the as-molded composite scaffolds had a diameter of 1 cm and were machined to a height of 1 cm.
  • the table below provides mechanical properties of the example PEKK scaffold reinforced with HA whiskers that was processed using a compression molding/particle leaching method such as, for example, the method 800 of FIG. 8 as implemented in the description above.
  • the mechanical properties of HA whisker reinforced PEKK were evaluated in uniaxial compression.
  • Tensile properties of the HA whisker reinforced PEKK scaffolds were evaluated prior to scaffold fabrication. As shown in the table, for a given reinforcement level, the compressive modulus decreased with increased porosity, and the yield strength decreased with increased porosity.
  • Scaffolds with 0% vol% HA whisker reinforcement and 75% and 90% porosity exhibited moduli of 69.5 and 0.75 MPa, while scaffolds with 40 vol% HA whisker reinforcement and 75%, 82% and 90% porosity exhibited moduli of 54.0, 15.7 and 0.23 MPa, respectively.
  • Scaffolds with 0 vol% HA whisker reinforcement and 75% and 90% porosity exhibited yield strengths of l.25MPa and 0.15 MPa, respectively.
  • Scaffolds with 40 vol% HA whisker reinforcement and 75%, 82% and 90% porosity exhibited yield strengths of 0.52 MPa, 0.13 MPa and 0.04 MPa, respectively.
  • the HA content also affected the modulus and failure strain of the scaffolds.
  • a scaffold having 75% porosity and 20 vol% reinforcement HA whisker exhibited modulus of 106.3 MPa, compared to a modulus of 69.5 MPa for scaffolds with 0 vol% HA whisker reinforcement.
  • the example methods and apparatus described herein offer synthetic porous composite material that may be used for synthetic bone substitutes for implant fixation, fraction fixation, synthetic bone graft substitutes, interbody spinal fusion, tissue engineering scaffolds, or other applications.
  • Many aspects of the of the porous composite material may be tailored to provide specific mechanical, biological, and surgical functions, such as, the polymer composition and molecular orientation, porosity and pore size of the porous matrix, or the HA reinforcement content, morphology, preferred orientation, and size.

Abstract

Des dispositifs implantables à usage orthopédique, y compris pour la colonne vertébrale et d'autres applications, sont formés d'échafaudages polymères renforcés poreux. Les échafaudages comprennent un polymère thermoplastique formant une matrice poreuse qui a des pores interconnectés en continu. La porosité et la taille des pores à l'intérieur de l'échafaudage sont formées sélectivement pendant la synthèse du matériau composite, et le matériau composite comprend une pluralité de particules de renforcement formées d'un seul tenant dans la matrice et incorporées dans la matrice et exposées sur les surfaces de pores. Les particules de renforcement permettent d'obtenir un renforcement, une bioactivité et/ou une biorésorption.
PCT/US2019/051704 2018-09-18 2019-09-18 Dispositifs implantables WO2020061176A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US16/134,453 US11179243B2 (en) 2007-02-28 2018-09-18 Implantable devices
US16/134,453 2018-09-18

Publications (1)

Publication Number Publication Date
WO2020061176A1 true WO2020061176A1 (fr) 2020-03-26

Family

ID=69887884

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2019/051704 WO2020061176A1 (fr) 2018-09-18 2019-09-18 Dispositifs implantables

Country Status (1)

Country Link
WO (1) WO2020061176A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113717432A (zh) * 2021-09-06 2021-11-30 常州华联医疗器械集团股份有限公司 一种高密度聚乙烯表面改性复合支架及其制备方法与应用
CN113842499A (zh) * 2021-09-17 2021-12-28 中国科学院宁波材料技术与工程研究所 一种超高分子量聚乙烯基复合材料及其制备方法及应用

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5866155A (en) * 1996-11-20 1999-02-02 Allegheny Health, Education And Research Foundation Methods for using microsphere polymers in bone replacement matrices and composition produced thereby
US7270679B2 (en) * 2003-05-30 2007-09-18 Warsaw Orthopedic, Inc. Implants based on engineered metal matrix composite materials having enhanced imaging and wear resistance
US20140236299A1 (en) * 2007-02-28 2014-08-21 Ryan K. Roeder Porous composite biomaterials and related methods
US9399086B2 (en) * 2009-07-24 2016-07-26 Warsaw Orthopedic, Inc Implantable medical devices

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5866155A (en) * 1996-11-20 1999-02-02 Allegheny Health, Education And Research Foundation Methods for using microsphere polymers in bone replacement matrices and composition produced thereby
US7270679B2 (en) * 2003-05-30 2007-09-18 Warsaw Orthopedic, Inc. Implants based on engineered metal matrix composite materials having enhanced imaging and wear resistance
US20140236299A1 (en) * 2007-02-28 2014-08-21 Ryan K. Roeder Porous composite biomaterials and related methods
US9399086B2 (en) * 2009-07-24 2016-07-26 Warsaw Orthopedic, Inc Implantable medical devices

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113717432A (zh) * 2021-09-06 2021-11-30 常州华联医疗器械集团股份有限公司 一种高密度聚乙烯表面改性复合支架及其制备方法与应用
CN113717432B (zh) * 2021-09-06 2023-03-31 常州华联医疗器械集团股份有限公司 一种高密度聚乙烯表面改性复合支架及其制备方法与应用
CN113842499A (zh) * 2021-09-17 2021-12-28 中国科学院宁波材料技术与工程研究所 一种超高分子量聚乙烯基复合材料及其制备方法及应用
CN113842499B (zh) * 2021-09-17 2022-07-01 中国科学院宁波材料技术与工程研究所 一种超高分子量聚乙烯基复合材料及其制备方法及应用

Similar Documents

Publication Publication Date Title
US20210177620A1 (en) Porous composite biomaterials and related methods
US11179243B2 (en) Implantable devices
US11911535B2 (en) Implantable medical device with thermoplastic composite body and method for forming thermoplastic composite body
US8715286B2 (en) Porous and nonporous materials for tissue grafting and repair
AU754630B2 (en) Bone substitutes
JP4101458B2 (ja) 代用骨材料
WO2002053105A2 (fr) Compositions et procedes destines a des applications biomedicales
US20150265745A1 (en) Porous and Nonporous Materials for Tissue Grafting and Repair
WO2020061176A1 (fr) Dispositifs implantables
US10105207B2 (en) Porous and nonporous materials for tissue grafting and repair
Dunkley The Development and Characterization of a Primarily Mineral Calcium Phosphate-Poly (ε-caprolactone) Biocomposite

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: 19863883

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: 19863883

Country of ref document: EP

Kind code of ref document: A1