US20050272153A1 - Bone tissue engineering by ex vivo stem cells ongrowth into three-dimensional trabecular metal - Google Patents

Bone tissue engineering by ex vivo stem cells ongrowth into three-dimensional trabecular metal Download PDF

Info

Publication number
US20050272153A1
US20050272153A1 US11045620 US4562005A US2005272153A1 US 20050272153 A1 US20050272153 A1 US 20050272153A1 US 11045620 US11045620 US 11045620 US 4562005 A US4562005 A US 4562005A US 2005272153 A1 US2005272153 A1 US 2005272153A1
Authority
US
Grant status
Application
Patent type
Prior art keywords
scaffold
tissue
implant
cells
method
Prior art date
Legal status (The legal status 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 status listed.)
Abandoned
Application number
US11045620
Inventor
Zou Xuenong
Haisheng Li
Cody Bunger
Original Assignee
Zou Xuenong
Haisheng Li
Cody Bunger
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

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56Porous materials, e.g. foams or sponges
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/28Bones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/32Joints for the hip
    • A61F2/34Acetabular cups
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/20Polysaccharides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/22Polypeptides or derivatives thereof, e.g. degradation products
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3604Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A61L27/3608Bone, e.g. demineralised bone matrix [DBM], bone powder
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54Biologically active materials, e.g. therapeutic substances
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/0068General culture methods using substrates
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06Animal cells or tissues; Human cells or tissues ; Not used, see subgroups
    • C12N5/0602Vertebrate cells
    • C12N5/0652Cells of skeletal and connective tissues; Mesenchyme
    • C12N5/0662Stem cells
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/30767Special external and/or bone-contacting surfaces, e.g. coating for improving bone ingrowth
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/3094Designing or manufacturing processes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/32Joints for the hip
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/32Joints for the hip
    • A61F2/36Femoral heads ; Femoral endoprostheses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/38Joints for elbows or knees
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/44Joints for the spine, e.g. vertebrae, spinal discs
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/46Special tools or methods for implanting or extracting artificial joints, accessories, bone grafts or substitutes, or particular adaptations therefor
    • A61F2/4644Preparation of bone graft, bone plugs or bone dowels, e.g. grinding or milling bone material
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/0077Special surfaces of prostheses, e.g. for improving ingrowth
    • A61F2002/0086Special surfaces of prostheses, e.g. for improving ingrowth for preferentially controlling or promoting the growth of specific types of cells or tissues
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/28Bones
    • A61F2002/2817Bone stimulation by chemical reactions or by osteogenic or biological products for enhancing ossification, e.g. by bone morphogenetic or morphogenic proteins [BMP] or by transforming growth factors [TGF]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/28Bones
    • A61F2002/2867Bone marrow
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2002/30001Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30108Shapes
    • A61F2002/30199Three-dimensional shapes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2002/30001Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30108Shapes
    • A61F2002/30199Three-dimensional shapes
    • A61F2002/30224Three-dimensional shapes cylindrical
    • A61F2002/30225Flat cylinders, i.e. discs
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2002/30001Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30667Features concerning an interaction with the environment or a particular use of the prosthesis
    • A61F2002/30677Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2002/30001Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30667Features concerning an interaction with the environment or a particular use of the prosthesis
    • A61F2002/30677Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
    • A61F2002/30678Gene therapy
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/30767Special external and/or bone-contacting surfaces, e.g. coating for improving bone ingrowth
    • A61F2002/3093Special external and/or bone-contacting surfaces, e.g. coating for improving bone ingrowth for promoting ingrowth of bone tissue
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/3094Designing or manufacturing processes
    • A61F2002/30981Designing or manufacturing processes using chemical vapour deposition [CVD]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/02Prostheses implantable into the body
    • A61F2/30Joints
    • A61F2/46Special tools or methods for implanting or extracting artificial joints, accessories, bone grafts or substitutes, or particular adaptations therefor
    • A61F2/4644Preparation of bone graft, bone plugs or bone dowels, e.g. grinding or milling bone material
    • A61F2002/4648Means for culturing bone graft
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2230/00Geometry of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2230/0063Three-dimensional shapes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2230/00Geometry of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2230/0063Three-dimensional shapes
    • A61F2230/0069Three-dimensional shapes cylindrical
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2310/00Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
    • A61F2310/00005The prosthesis being constructed from a particular material
    • A61F2310/00161Carbon; Graphite
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2310/00Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
    • A61F2310/00005The prosthesis being constructed from a particular material
    • A61F2310/00179Ceramics or ceramic-like structures
    • A61F2310/00293Ceramics or ceramic-like structures containing a phosphorus-containing compound, e.g. apatite
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2310/00Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
    • A61F2310/00005The prosthesis being constructed from a particular material
    • A61F2310/00341Coral, e.g. aragonite, porite
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2310/00Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
    • A61F2310/00389The prosthesis being coated or covered with a particular material
    • A61F2310/00395Coating or prosthesis-covering structure made of metals or of alloys
    • A61F2310/00419Other metals
    • A61F2310/00491Coating made of niobium or Nb-based alloys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2310/00Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
    • A61F2310/00389The prosthesis being coated or covered with a particular material
    • A61F2310/00395Coating or prosthesis-covering structure made of metals or of alloys
    • A61F2310/00419Other metals
    • A61F2310/00544Coating made of tantalum or Ta-based alloys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2310/00Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
    • A61F2310/00389The prosthesis being coated or covered with a particular material
    • A61F2310/00976Coating or prosthesis-covering structure made of proteins or of polypeptides, e.g. of bone morphogenic proteins BMP or of transforming growth factors TGF
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2310/00Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
    • A61F2310/00389The prosthesis being coated or covered with a particular material
    • A61F2310/00976Coating or prosthesis-covering structure made of proteins or of polypeptides, e.g. of bone morphogenic proteins BMP or of transforming growth factors TGF
    • A61F2310/00982Coating made of collagen
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/22Lipids, fatty acids, e.g. prostaglandins, oils, fats, waxes
    • A61L2300/222Steroids, e.g. corticosteroids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/252Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/606Coatings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/64Animal cells
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2400/00Materials characterised by their function or physical properties
    • A61L2400/18Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2430/00Materials or treatment for tissue regeneration

Abstract

Adult autologous stem cells cultured on a porous, three-dimensional tissue scaffold-implant for bone regeneration by the use of a hyaluronan and/or dexamethasone to accelerate bone healing alone or in combination with recombinant growth factors or transfected osteogenic genes. The scaffold-implant may be machined into a custom-shaped three-dimensional cell culture system for support of cell growth, reservoir for peptides, recombinant growth factors, cytokines and antineoplastic drugs in the presence of a hyaluronan and/or dexamethasone alone or in combination with growth factors or transfected osteogenic genes, to be assembled ex vivo in a tissue incubator for implantation into bone tissue.

Description

    RELATED APPLICATIONS
  • [0001]
    The application claims the benefit of U.S. Provisional Application No. 60/539,661, filed on Jan. 27, 2004, which is incorporated herein in its entirety.
  • FIELD
  • [0002]
    The invention relates to tissue generation. More particularly, the invention relates to three-dimensional tissue generation by ex vivo three-dimensional cell culture methods using porous, three-dimensional tissue scaffold-implants.
  • BACKGROUND
  • [0003]
    The current trend of tissue engineering technology is toward the development of biomaterials for repairing tissue defects or to enhance fixation of implants to the host tissue. Basic requirements include a scaffold-implant conductive to cell attachment and maintenance of cell function, together with a rich source of progenitor cells. Biomaterials in combination with cells from ex-vivo cultures will not only accelerate the tissue healing, but also increase the biocompatibility of scaffold-implants to shorten the hospitalization, and improved long-term function of the devices. In particular, patients with large defects, impaired bone healing and cancer disease in the region of repair shall benefit from this new technology. One regenerative tissue engineering approach involves a process known as “tissue induction”, whereby a two or three-dimensional polymer or mineral scaffold-implant without cells is implanted into a patient. With tissue induction, tissue generation occurs through ingrowth of surrounding tissue into the scaffold-implant.
  • [0004]
    Another approach to tissue generation, known as “cell transplantation”, involves seeding a scaffold-implant with cells, cytokines, and other growth-related molecules, then culturing and implanting the scaffold-implant into the subject to induce the growth of new tissue. Cultured cells are infused in a biodegradable or non-biodegradable scaffold-implant, which may be placed in a bioreactor in-vitro to allow the cells to proliferate before the cells containing scaffold-implant is implanted in the patient. Alternatively, the cell-seeded scaffold-implant may be directly implanted, in which case the patient's body acts as an in-vivo bioreactor. Once implanted, in-vivo cellular proliferation and, in the case of absorbable scaffold-implants, concomitant bio-absorption of the scaffold-implant, proceeds.
  • [0005]
    In both types of tissue engineering, i.e., tissue induction and cell transplantation, the scaffold-implant, whether or not bio-absorbable, must be biocompatible, such that it does not invoke an adverse immune response from, or result in toxicity to, the patient.
  • [0006]
    Several types of materials have been investigated for use as seeding scaffold-implants, including metals, ceramics, polymers, and polymer-coated metals and ceramics. Existing scaffold-implants may be manufactured by solvent casting, shaping sections with machining, 3D printing, or molded collagen/cell constructs. While the aforementioned scaffold-implant materials are primarily for industrial applications, the fabrication of hydroxyapatite scaffold-implants using selective laser sintering and polymer-coated calcium phosphate powder, have been investigated. Additional post-processing, such as high temperature heating which burns out the binder, and then higher temperature sintering which fuses the powder together, is required to strengthen the scaffold-implant.
  • [0007]
    Whichever type of scaffold-implant is selected, a purpose of the scaffold-implant is to support cells, which, after being seeded into the device, cling to the interstices of the scaffold-implant, replicate, produce their own extracellular matrices, and organize into the target tissue. For example, in the case of bone regeneration, the optimal pore size for maximum tissue growth ranges from 200-400 mircons (μm). Therefore, the material or materials used for fabricating the scaffold-implant should have this pore size (200-400 μm) and have sufficient rigidity and biomechanical properties to support loads that are used for generating bone tissue.
  • [0008]
    Scaffold-implants fabricated from a material such as hydroxyapatite, which is useful for supporting bone cells, are too brittle and non-pliable to act as scaffolding for muscle or tendons. Many of the polymers, and the polymer-coated metals and ceramics present a challenge to seeding cells in three-dimensional scaffolds. None of the known scaffold-implant materials allow growth of cells to a depth of greater than about 250 μm, which is a generally accepted practical limit on the depth to which cells and nutrients can diffuse into scaffold-implants having the desired porosities. Even if cells could be made to diffuse to greater depths, it is generally believed that to support cell growth and avoid or at least curtail apoptosis at these depths, the scaffold-implant must also support some form of vasculature to promote angiogenesis; none of the earlier mentioned scaffold-implant fabrication methods, however, allow for incorporation of blood vessels.
  • [0009]
    Porous, three-dimensional metallic structures have recently been developed for potential application in reconstructive orthopaedics and other surgical disciplines. Such structures are described in U.S. Pat. No. 5,282,861 entitled “Open Cell Tantalum Structures For Cancellous Bone Implants And Cell And Tissue Receptors” issued to Kaplan; U.S. Pat. No. 5,443,515 entitled “Vertebral Body Prosthetic Implant With Slidably Positionable Stabilizing Member” issued to Cohen et al.; U.S. Pat. No. 5,755,809 entitled “Femoral Head Core Channel Filling Prothesis” issued to Cohen et al.; U.S. Pat. No. 6,063,442 entitled “Bonding Of Porous Materials To Other Materials Utilizing Chemical Vapor Deposition” issued to Cohen et al.; and U.S. Pat. No. 6,087,553 entitled “Implantable Metallic Open-Celled Lattice/Polyethylene Composite Material And Devices” issued to Cohen et al., the disclosures of which are incorporated herein by reference. The porous, three-dimensional metallic structure is a bio-compatible material having a three-dimensional network of continuously interconnected channels or pores which define a three-dimensional porosity, i.e., volume porosity, ranging from 50 to 90% (higher than all other known implant materials). This high bulk volume porosity readily facilitates nutrient diffusion and media circulation.
  • [0010]
    The porous, three-dimensional metallic structures may be fabricated using a vapor deposition/infiltration process wherein tantalum, which has a long history of medical uses, or other bio-compatible metal or material is vaporized at high temperature and precipitated as a thin layer onto a carbon lattice. The coating of tantalum or other metal enhances or improves the strength or mechanical characteristics of the carbon lattice.
  • [0011]
    As a scaffold for “bone induction,” preliminary animal studies with transcortical (bone conduction) porous, three-dimensional metallic structures have been shown to support rapid and extensive bone ingrowth. For example, tissue response to porous tantalum acetabular cups indicates that the porous tantalum material is effective for biologic fixation. The biomechanical property of the porous tantalum biomaterial is sufficient to withstand physiological load for specific applications, such as an acetabular cup, a spinal fusion, and a vertebral body replacement in fractures or in metastatic cancer disease. As a scaffold for “cell transplantation,” porous, three-dimensional metallic structures can extend culturing of multipotent hematopoietic progenitors without cytokine augmentation and enhance maintenance and retroviral transduction of primitive hematopoietic progenitor cells.
  • [0012]
    Hyaluronan possesses biochemical and physical properties suitable to perform an important role in the early events of osteogenesis as well as in many other tissues. A low-molecular weight hyaluronan fully expresses the in-vitro steogenic potential of mesenchymal cells through the subsequent proliferation and differentiation of osteoprogenitor cells using proper conditions. Locally applied high-molecular hyaluronan of MW 1900 kDa also has been shown to be capable of accelerating new bone formation through mesenchymal cell differentiation in femur wounds. Hyaluronan at a low concentration (0.5 mg/mL) has been shown to increase the development of porcine embryos in culture.
  • SUMMARY
  • [0013]
    One aspect is a three-dimensional tissue scaffold-implant for supporting tissue (e.g., bone) on-growth. The tissue scaffold-implant comprises a lattice having a matrix of interconnected pores which form surfaces in three dimensions; and an inert, biocompatible material covering the surfaces. The surfaces of the scaffold-implant define a high surface area relative to a volume of the scaffold-implant.
  • [0014]
    Another aspect is a method of forming tissue (e.g., bone). The method comprises providing a three-dimensional tissue scaffold comprising a lattice having a matrix of interconnected pores which form surfaces in three dimensions, and an inert, biocompatible material covering the surfaces; covering the biocompatible material covered surfaces of the scaffold with cells; and culturing the scaffold to grow tissue on and in the scaffold.
  • [0015]
    Yet another aspect is a method of making an implant for supporting tissue (e.g., bone) on-growth. This method comprises providing a three-dimensional tissue scaffold comprising a lattice having a matrix of interconnected pores which form surfaces in three dimensions, and an inert, biocompatible material covering the surfaces; and covering the biocompatible material covered surfaces of the scaffold with cells.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • [0016]
    FIG. 1 is a flow chart depicting an embodiment of the method of the present invention.
  • [0017]
    FIG. 2 is a bar graph quantifying stem cells binding to a coralline hydroxyapatite disc and uncoated and coated porous tantalum discs, after a 24-hour incubation at 37° C. and normalized to the uncoated TA disc.
  • [0018]
    FIGS. 3A and 3B are Hoechst stained fluorescent micrographs at 50× original magnification and 20× original magnification respectively, showing the growing stem cells in the pores of porous tantalum after 7 days of incubation.
  • [0019]
    FIGS. 4A and 4B are histological micrographs at 20× original magnification and 6.25× original magnification respectively, after 8 weeks of implantation in pigs.
  • [0020]
    FIG. 5 is a scanning electronic micrograph of the three-dimensional tissue scaffold-implant.
  • [0021]
    FIG. 6 is a histological micrograph of the three-dimensional tissue scaffold-implant after 12 weeks of implantation in a pig.
  • DETAILED DESCRIPTION
  • [0022]
    The tissue formation method of the present invention utilizes an ex vivo cell culture system and a porous, three-dimensional metallic structure or tissue scaffold of a desired shape and size, which will be implanted into the body of an animal or human being (hereinafter scaffold-implant). The cell culture system induces early stage cell proliferation and differentiation on and in the tissue scaffold-implant, resulting in tissue generation. The tissue formation method of the present invention is especially useful for generating bone tissue. The method of the invention may also be used to generate connective tissue and hematopoietic tissue.
  • [0023]
    The flow chart of FIG. 1 depicts an embodiment of the tissue formation method of the present invention. In step 10 of the method, a porous, three-dimensional tissue scaffold-implant is fabricated in a desired shape and size, e.g., hip implant, spinal implant, knee implant, etc. For example, the scaffold-implant may be shaped and sized as a prosethetic acetabular cup such as the one disclosed in U.S. Pat. No. 5,443,519 entitled “Prosthetic Ellipsoidal Acetabular Cup,” issued to Averill et al. In another example, the scaffold-implant may be shaped and sized as a prosethetic femoral component such as the one disclosed in U.S. Pat. No. 5,702,487 entitled “Prosethetic Device” issued to Averill et al.
  • [0024]
    In one embodiment, the scaffold-implant may be fabricated as a single unitary member. In an alternative embodiment, the scaffold-implant may be fabricated as a single, integral member formed by two or more separately fabricated sections which are mechanically assembled together in a conventional manner. In still another embodiment, the scaffold-implant may be fabricated as an assembly of two or more cooperating, unitary and/or integral members (e.g., acetabular cup and femoral stem/ball assembly).
  • [0025]
    The porous, three-dimensional tissue scaffold-implant may comprise a carbon lattice having a strut or ligament skeleton which forms a three-dimensional network of continuously interconnected channels or pores each roughly approximating a dodecahedron, which create a series of continuous microniches and form surfaces of the lattice in three dimensions; and a thin film of an inert, bio-compatible metal or other bio-compatible material, which covers the surfaces.
  • [0026]
    The carbon lattice may be formed as a single, unitary member of a desired shape and size, or in sections of desired shapes and sizes to be mechanically assembled. The carbon lattice is substantially rigid, therefore, it may be machined into a bone regeneration tool of a desired shape and size using conventional machining methods.
  • [0027]
    The inert, bio-compatible metal or other bio-compatible material may be applied to the surfaces of the carbon lattice using conventional vapor depositing and infiltrating methods. In a preferred embodiment, the inert, biocompatible metal comprises tantalum. In other embodiments, the inert, biocompatible metal may comprise niobium or alloys of tantalum and niobium.
  • [0028]
    The completed porous, three-dimensional tissue scaffold-implant forms a three-dimensional network of continuously interconnected, channels or pores which define a three-dimensional porosity (volume porosity). In one embodiment, the tissue scaffold implant may comprise channels or pores having an average diameter of 400 to 500 μm and a volume porosity ranging from about 50 to about 90%. The geometry of the interconnected pores and surface texturing arising from the metal vapor deposition process produce high surface area-to-volume ratio. The large pores and surfaces allow attachment of proteins, peptides and differentiated and undifferentiated cells. After fabrication, the scaffold-implant may be coated with substrate molecules such as fibronectin and collagens which aid in the attachment of the proteins, peptides and differentiated and undifferentiated cells.
  • [0029]
    In step 20, a hyaluronan (also referred to as hyaluronic acid or sodium hyaluronate) or a hyaluronan, dexamethasone, one or more growth factors and/or osteogenic genes is (are) applied to the surfaces of the tissue scaffold-implant to stimulate early cell proliferation and differentiation, therefore accelerating tissue generation. Sodium hyaluronate is a natural high-viscosity anionic mucopolysaccharide with alternating beta (1-3) glucuronide and beta (1-4) glucosaminidic bonds. It is commonly found in the umbilical cord, in vitreous humor, in synovial fluid, in pathologic joints, in group A and C hemolytic streptococci, and in Wharton's jelly. Dexamethasone is a synthetic steroid compound. In one embodiment, the tissue scaffold-implant may be treated with a low concentration (4 mg/mL) of sodium hyaluronate to induce in-vitro, early stage stem cell proliferation and differentiation on and in the tissue scaffold-implant (after performing steps 30 and 40 to be described further on). In another embodiment, the tissue scaffold-implant may be treated with a high concentration (10-20 mg/mL) of sodium hyaluronate which forms a hydro gel with the stem cells in the tissue scaffold-implant intraoperatively.
  • [0030]
    In step 30 of the method, a cell transplantation process is performed on the porous, three-dimensional tissue scaffold-implant. In an embodiment of the cell transplantation process, the tissue scaffold-implant is seeded with living cells, which may comprise differentiated, undifferentiated or gene transfected cells. Examples of differentiated or undifferentiated cells include without limitation bone marrow cells, osteoblasts, mesenchymal stem cells, embryonic stem cells, endothelial cells. In another embodiment of the cell transplantation process, the tissue scaffold-implant is seeded with living cells and proteins, peptides, transcript factors, osteogenic genes, cytokines, therapeutic agents, and growth factors.
  • [0031]
    The living cells and other factors can be entrapped and delivered in the tissue scaffold-implant by means of a versatile self-assembly method. In this self-assembly method cellular matrix fibrils are formed with methylated collagen (type I) and hyaluronic acid, or chitosan, which entrap and deliver living cells and other factors. The cellular matrix fibrils are then combined with an outer-layer membrane comprising a polymer such as alginate, hydroxylethyl methacrylate (HEMA), or a terpolymer of hydroxylethyl methacrylate (HEMA), methy methacrylate (MMA) and methylacric acid (MAA) by complex sandwich conjugation achieved, for example, using a complex coacervation process, to protect transplanted allogeneic cells from immune attacks and to sustain release of the stimulating factors and therapeutic agents. In one embodiment, the membrane may be several micrometers to about 100 micrometers thick. The thickness of the membrane may be adjusted by controlling the concentrations and contact time of polyelectrolytes in the complex sandwich conjugation process.
  • [0032]
    The surface features (the texture on the surface of the metal resulting from the CVD of the metal) and the open, highly interconnected pores of the tissue scaffold-implant readily facilitate nutrient diffusion and media circulation and thus will operate as conduits for cell infusion, adhesion, mass transfer, or to stimulate angiogenesis for blood flow.
  • [0033]
    In an alternate embodiment, the application of the hyaluronan or the hyaluronan, dexamethasone, one or more growth factors and/or osteogenic genes, to the surfaces of the tissue scaffold-implant (step 20) may be performed during the cell transplantation process of step 30.
  • [0034]
    In step 40, after seeding, the scaffold-implant is cultured in a bioreactor to generate the desired tissue. In one embodiment, the culturing step is an ex-vivo process. Ex-vivo culturing may be performed in a broth medium, e.g., Dulbecco's modified Eagle's medium (DMEM) available from HyClone, plus 10% fetal calf serum, which is placed in an incubator e.g., perfusion or spiner flask bioreactor or a rotating bioreactor. The broth medium and incubator operate as an in-vitro bioreactor. In one embodiment, the incubator may provide a humidified atmosphere of 95% air and 5% CO2 at 37° C. In addition, the incubator may be of the type which provides static, dynamic medium flow, pulsatile air flow, microgravity and multidirectional gravity culturing conditions. The scaffold-implant may then be implanted (in-vivo) into an animal or patient's body.
  • [0035]
    In another embodiment, the culturing step is an in-vivo process. In-vivo culturing may be performed in an animal or a patient by directly implanting the scaffold-implant in the animal or the patient. In this embodiment, the animal or the patient' body operates as an in-vivo bioreactor.
  • [0036]
    In still an alternate embodiment, the culturing step can be performed intraoperatively. In this embodiment, cells are taken from the animal or patient and applied to the scaffold-implant. The scaffold-implant is then implanted in the animal or patient.
  • [0037]
    FIG. 2 is a bar graph quantifying stem cells binding to 1) a coralline hydroxyapatite (HA) disc; 2) an uncoated porous, tantalum-based, three-dimensional tissue scaffold-implant (TA) configured as a disc; 3) a TA disc coated with gelatin; 4) a TA disc coated with type I collagen; and 5) a TA disc coated with fibronectin, n=9 (repeated test), after a 24-hour incubation at 37° C. and normalized to the uncoated TA disc. In the graph, the stem cells are 3H-thymidine labeling cells.
  • [0038]
    FIGS. 3A and 3B are fluorescent micrographs showing the growing cells in the pores of a porous, tantalum-based, three-dimensional tissue scaffold-implant configured as a disc after 7 days of incubation (Hoechst staining). As can be seen in FIG. 3A, at day 7, porcine bone marrow stem cells depicted funicular proliferations of spindle cells on the pore surface and within the pores. As shown in FIG. 3B, growing stem cells in the pores mainly distributed on the surface areas of disc (superior) where the cells were loaded on. Only a few stem cells had grown into the central pores and down to other surface areas of the disc (inferior) where the disc was seated on a well.
  • [0039]
    FIGS. 4A and 4B are histological micrographs which show, after 8 weeks of implantation in pigs, ectopic bone formation after autologous bone marrow stem cells cultured with a tantalum-based, three-dimensional tissue scaffold-implant for 7 days of incubation. Basic fuchsin and light green staining revealed the bone is green G and fibrous tissue is red R. The black structure B is porous tantalum strut. Specifically, FIG. 4A shows bone forming in the pore surface and the pores and FIG. 4B shows a layer of de novo bone formation at the surface area of the scaffold-implant.
  • [0040]
    FIG. 5 is a scanning electronic micrograph of the three-dimensional tissue scaffold-implant. As can be seen, the scaffold-implant has a volume porosity of about 50% to about 90% with interconnecting pores, allowing approximately 2-3 times greater bone ingrowth compared to conventional porous coatings.
  • [0041]
    FIG. 6 is a histological micrograph of the three-dimensional tissue scaffold-implant after 12 weeks of implantation in a pig. As can be observed, there is bone formation from intraoperative conjugation of autologous bone marrow stem cells and hyaluronic acid gel in the tissue scaffold-implant. Basic fuchsin and light green staining revealed the bone is green G and fibrous tissue is red R. The black structure B is porous tantalum strut.
  • [0042]
    While the foregoing invention has been described with reference to the above, various modifications and changes can be made without departing from the spirit of the invention. Accordingly, all such modifications and changes are considered to be within the scope of the appended claims.

Claims (37)

  1. 1. A three-dimensional tissue scaffold-implant for supporting tissue on-growth, the scaffold-implant comprising:
    a lattice having a matrix of interconnected pores which form surfaces in three dimensions;
    an inert, bio-compatible material covering the surfaces; and
    at least one of a hyaluronan, dexamethasone, protein, peptide, transcript factor, cytokine, therapeutic agent, chitosan, polymer, osteogenic gene and growth factor, covering the material.
  2. 2. The tissue scaffold-implant of claim 1, wherein the inert, biocompatible material comprises a metal.
  3. 3. The tissue scaffold-implant of claim 2, wherein the metal comprises tantalum.
  4. 4. The tissue scaffold-implant of claim 1, wherein the inert, biocompatible material comprises a metal alloy.
  5. 5. The tissue scaffold-implant of claim 1, further comprising living cells covering the biocompatible material, the cells selected from the group consisting of bone marrow cells, osteoblasts, mesenchymal stem cells, embryonic stem cells, gene transfected cells, endothelial cells and combinations thereof.
  6. 6. The tissue scaffold-implant of claim 1, further comprising tissue grown over the bio-compatible material.
  7. 7. The tissue scaffold-implant of claim 6, wherein the tissue comprises bone.
  8. 8. A method of forming tissue, the method comprising:
    providing a three-dimensional tissue scaffold comprising a lattice having a matrix of interconnected pores which form surfaces in three dimensions, and an inert, biocompatible material covering the surfaces;
    covering the material covered surfaces of the scaffold with living cells; and
    culturing the scaffold to grow tissue on and in the scaffold.
  9. 9. The method of claim 8, wherein prior to the culturing step, further comprising the step of applying at least one of a hyaluronan, dexamethasone, protein, peptide, transcript factor, cytokine, therapeutic agent, chitosan, polymer, osteogenic gene and growth factor, to the material covered surfaces.
  10. 10. The method of claim 9, wherein the applying step includes encapsulating the at least one of the hyaluronan, dexamethasone, protein, peptide, transcript factor, cytokines therapeutic agent, chitosan, polymer, osteogenic gene and growth factor.
  11. 11. The method of claim 10, wherein the encapsulation is performed by complex sandwich conjugation with a polymeric material.
  12. 12. The method of claim 11, wherein the culturing step is performed by placing the scaffold in a medium and incubating the medium and scaffold.
  13. 13. The method of claim 12, further comprising the step of implanting the scaffold in a body of one of an animal and a human being.
  14. 14. The method of claim 9, wherein the culturing step is performed by implanting the scaffold in the body of one of an animal and a human being.
  15. 15. The method of claim 10, wherein the culturing step is performed by implanting the scaffold in the body of one of an animal and a human being.
  16. 16. The method of claim 8, wherein the culturing step is performed by placing the scaffold in a medium and incubating the medium and scaffold.
  17. 17. The method of claim 16, further comprising the step of implanting the scaffold in a body of one of an animal and a human being.
  18. 18. The method of claim 8, wherein the culturing step is performed by implanting the scaffold in the body of one of an animal and a human being.
  19. 19. The method of claim 8, wherein the covering step is performed by cell transplantation.
  20. 20. The method of claim 8, wherein the inert, biocompatible metal comprises tantalum.
  21. 21. The method of claim 8, wherein the living cells are selected from the group consisting of bone marrow cells, osteoblasts, mesenchymal stem cells, embryonic stem cells, gene transfected cells, endothelial cells and combinations thereof.
  22. 22. The method of claim 8, wherein the tissue comprises bone.
  23. 23. A method of making an implant for supporting tissue on-growth, the method comprising:
    providing a three-dimensional tissue scaffold comprising a lattice having a matrix of interconnected pores which form surfaces in three dimensions, and an inert, biocompatible metal covering the surfaces; and
    covering the metal covered surfaces of the scaffold with living cells.
  24. 24. The method of claim 23, further comprising the step of applying at least one of a hyaluronan, dexamethasone, protein, peptide, transcript factor, cytokine, therapeutic agent, chitosan, polymer, osteogenic gene and growth factor, to the metal covered surfaces.
  25. 25. The method of claim 24, wherein the applying step includes encapsulating at least one of the hyaluronan, dexamethasone, protein, peptide, transcript factor, cytokines, therapeutic agent, chitosan, polymer, osteogenic gene and growth factor.
  26. 26. The method of claim 25, wherein the encapsulation is performed by complex sandwich conjugation with a polymeric material.
  27. 27. The method of claim 26, further comprising the step of culturing the scaffold to grow tissue on and in the scaffold.
  28. 28. The method of claim 27, wherein the culturing step is performed by placing the scaffold in a medium and incubating the medium and scaffold.
  29. 29. The method of claim 23, further comprising the step of culturing the scaffold to grow tissue on and in the scaffold.
  30. 30. The method of claim 29, wherein the culturing step is performed by placing the scaffold in a medium and incubating the medium and scaffold.
  31. 31. The method of claim 25, wherein the culturing step is performed by implanting the scaffold in the body of one of an animal and a human being.
  32. 32. The method of claim 23, wherein the covering step is performed by cell transplantation.
  33. 33. The method of claim 23, wherein the inert, biocompatible material comprises tantalum.
  34. 34. The method of claim 23, wherein the living cells are selected from the group consisting of bone marrow cells, osteoblasts, mesenchymal stem cells, embryonic stem cells, gene transfected cells, endothelial cells and combinations thereof.
  35. 35. The method of claim 34, wherein cells are encapsulated in at least one of a hyaluronan and collagen, or chitosan with a polymeric material by complex sandwich conjugation.
  36. 36. The method of claim 28, wherein the culturing method is performed in one of or any combination of a static, dynamic medium flow, pulsatile flow, microgravity and multidirectional gravity culturing environment.
  37. 37. The method of claim 23, wherein the tissue comprises bone.
US11045620 2004-01-27 2005-01-27 Bone tissue engineering by ex vivo stem cells ongrowth into three-dimensional trabecular metal Abandoned US20050272153A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US53966104 true 2004-01-27 2004-01-27
US11045620 US20050272153A1 (en) 2004-01-27 2005-01-27 Bone tissue engineering by ex vivo stem cells ongrowth into three-dimensional trabecular metal

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US11045620 US20050272153A1 (en) 2004-01-27 2005-01-27 Bone tissue engineering by ex vivo stem cells ongrowth into three-dimensional trabecular metal
US11869361 US8895046B2 (en) 2004-01-27 2007-10-09 Orthopaedic implant for supporting tissue growth and methods of forming the implant and tissue
US14218039 US9795715B2 (en) 2004-01-27 2014-03-18 Bone tissue engineering by ex vivo stem cells ongrowth into three-dimensional trabecular metal
US14999245 US20160228614A1 (en) 2004-01-27 2016-04-14 Bone tissue engineering by ex vivo stem cells ongrowth into three-dimensional trabecular metal
US15710398 US20180008747A1 (en) 2004-01-27 2017-09-20 Bone tissue engineering by ex vivo stem cells ongrowth into three-dimensional trabecular metal

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US11869361 Continuation US8895046B2 (en) 2004-01-27 2007-10-09 Orthopaedic implant for supporting tissue growth and methods of forming the implant and tissue

Publications (1)

Publication Number Publication Date
US20050272153A1 true true US20050272153A1 (en) 2005-12-08

Family

ID=35449477

Family Applications (5)

Application Number Title Priority Date Filing Date
US11045620 Abandoned US20050272153A1 (en) 2004-01-27 2005-01-27 Bone tissue engineering by ex vivo stem cells ongrowth into three-dimensional trabecular metal
US11869361 Active 2029-12-24 US8895046B2 (en) 2004-01-27 2007-10-09 Orthopaedic implant for supporting tissue growth and methods of forming the implant and tissue
US14218039 Active 2027-11-19 US9795715B2 (en) 2004-01-27 2014-03-18 Bone tissue engineering by ex vivo stem cells ongrowth into three-dimensional trabecular metal
US14999245 Abandoned US20160228614A1 (en) 2004-01-27 2016-04-14 Bone tissue engineering by ex vivo stem cells ongrowth into three-dimensional trabecular metal
US15710398 Pending US20180008747A1 (en) 2004-01-27 2017-09-20 Bone tissue engineering by ex vivo stem cells ongrowth into three-dimensional trabecular metal

Family Applications After (4)

Application Number Title Priority Date Filing Date
US11869361 Active 2029-12-24 US8895046B2 (en) 2004-01-27 2007-10-09 Orthopaedic implant for supporting tissue growth and methods of forming the implant and tissue
US14218039 Active 2027-11-19 US9795715B2 (en) 2004-01-27 2014-03-18 Bone tissue engineering by ex vivo stem cells ongrowth into three-dimensional trabecular metal
US14999245 Abandoned US20160228614A1 (en) 2004-01-27 2016-04-14 Bone tissue engineering by ex vivo stem cells ongrowth into three-dimensional trabecular metal
US15710398 Pending US20180008747A1 (en) 2004-01-27 2017-09-20 Bone tissue engineering by ex vivo stem cells ongrowth into three-dimensional trabecular metal

Country Status (1)

Country Link
US (5) US20050272153A1 (en)

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007121345A2 (en) * 2006-04-13 2007-10-25 Case Western Reserve University Biomaterial implants
US20080081362A1 (en) * 2006-09-29 2008-04-03 Daniel Keeley Multilayered Composite for Organ Augmentation and Repair
WO2008065565A3 (en) * 2006-11-30 2008-07-24 Hannes Dahnke Energy resolved imaging
US20090275011A1 (en) * 2008-04-30 2009-11-05 Johann Eibl Sessile stem cells
US20100305696A1 (en) * 2007-05-24 2010-12-02 The Trustees Of Columbia University In The City Of New York Hybrid soft tissue implants from progenitor cells and biomaterials
WO2011104657A1 (en) 2010-02-23 2011-09-01 Sheltagen Medical Ltd. Three-dimensional bone implant and method for producing same
US8475505B2 (en) 2008-08-13 2013-07-02 Smed-Ta/Td, Llc Orthopaedic screws
WO2013106318A1 (en) * 2012-01-09 2013-07-18 Zimmer, Inc. Composite device that combines porous metal and bone stimuli
US20130268087A1 (en) * 2011-11-23 2013-10-10 Amendia Inc. Bone graft
CN103656752A (en) * 2012-09-25 2014-03-26 中南大学 Method for strengthening and toughening biological ceramic material by use of graphene and preparing artificial bone prepared from material
US9358056B2 (en) 2008-08-13 2016-06-07 Smed-Ta/Td, Llc Orthopaedic implant
US9561354B2 (en) 2008-08-13 2017-02-07 Smed-Ta/Td, Llc Drug delivery implants
US9616205B2 (en) 2008-08-13 2017-04-11 Smed-Ta/Td, Llc Drug delivery implants
US9700431B2 (en) 2008-08-13 2017-07-11 Smed-Ta/Td, Llc Orthopaedic implant with porous structural member
US9730959B2 (en) 2011-12-29 2017-08-15 “Nextgen” Company Limited Biocomposite for regeneration of injured tissue and organs, a kit for making the biocomposite, a method of making the biocomposite and a method of treating injuries

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040081704A1 (en) * 1998-02-13 2004-04-29 Centerpulse Biologics Inc. Implantable putty material
US20020114795A1 (en) * 2000-12-22 2002-08-22 Thorne Kevin J. Composition and process for bone growth and repair
US20050272153A1 (en) 2004-01-27 2005-12-08 Zou Xuenong Bone tissue engineering by ex vivo stem cells ongrowth into three-dimensional trabecular metal
CN103251449B (en) 2005-10-13 2016-03-02 斯恩蒂斯有限公司 Drug packaging
US7718616B2 (en) * 2006-12-21 2010-05-18 Zimmer Orthobiologics, Inc. Bone growth particles and osteoinductive composition thereof
US9045735B2 (en) * 2007-04-03 2015-06-02 The Cleveland Clinic Foundation Enrichment of tissue-derived adult stem cells based on retained extracellular matrix material
WO2010003104A3 (en) * 2008-07-02 2010-11-25 Allergan, Inc. Compositions and methods for tissue filling and regeneration
US20100003674A1 (en) * 2008-07-03 2010-01-07 Cope Frederick O Adult stem cells, molecular signatures, and applications in the evaluation, diagnosis, and therapy of mammalian conditions
EP2266635A1 (en) * 2009-06-26 2010-12-29 Aarhus Universitet Three-dimensional nanostructured hybrid scaffold and manufacture thereof
US8905914B2 (en) * 2010-11-03 2014-12-09 Ethicon Endo-Surgery, Inc. Gastric band device and method
WO2012068135A1 (en) 2010-11-15 2012-05-24 Zimmer Orthobiologics, Inc. Bone void fillers
EP2652127B1 (en) 2010-12-15 2018-04-04 Health Corporation - Rambarn Vertical bone augmentation using endothelial progenitor cells
US9381683B2 (en) 2011-12-28 2016-07-05 DePuy Synthes Products, Inc. Films and methods of manufacture
US20160095958A1 (en) * 2013-05-28 2016-04-07 The Johns Hopkins University Bone regeneration using stromal vascular fraction, platelet-derived growth factor-rich hydrogel, three-dimensional printed poly-epsilon-caprolactone scaffolds
US20160324642A1 (en) * 2013-12-30 2016-11-10 The New York Stem Cell Foundation Tissue grafts and methods of making and using the same
CN104697499B (en) * 2014-08-29 2017-09-01 北京精密机电控制设备研究所 Three degrees of freedom applied to one kind of visual positioning method under microgravity
WO2018031800A1 (en) * 2016-08-10 2018-02-15 New York Stem Cell Foundation, Inc. Surface functionalized implant and method of generating the same

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5282861A (en) * 1992-03-11 1994-02-01 Ultramet Open cell tantalum structures for cancellous bone implants and cell and tissue receptors

Family Cites Families (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4487808A (en) * 1982-04-22 1984-12-11 Astra Meditec Aktiebolag Medical article having a hydrophilic coating
US5160490A (en) * 1986-04-18 1992-11-03 Marrow-Tech Incorporated Three-dimensional cell and tissue culture apparatus
US5278063A (en) * 1989-09-28 1994-01-11 Board Of Regents The University Of Texas System Chemical modification of promote animal cell adhesion on surfaces
WO1993013815A1 (en) * 1992-01-13 1993-07-22 Lucocer Aktiebolag An implant
US5443519A (en) * 1993-04-22 1995-08-22 Implex Corporation Prosthetic ellipsoidal acetabular cup
US5409703A (en) * 1993-06-24 1995-04-25 Carrington Laboratories, Inc. Dried hydrogel from hydrophilic-hygroscopic polymer
US5593451A (en) * 1994-06-01 1997-01-14 Implex Corp. Prosthetic device and method of implantation
US5509899A (en) * 1994-09-22 1996-04-23 Boston Scientific Corp. Medical device with lubricious coating
US6017577A (en) * 1995-02-01 2000-01-25 Schneider (Usa) Inc. Slippery, tenaciously adhering hydrophilic polyurethane hydrogel coatings, coated polymer substrate materials, and coated medical devices
US5612052A (en) * 1995-04-13 1997-03-18 Poly-Med, Inc. Hydrogel-forming, self-solvating absorbable polyester copolymers, and methods for use thereof
US6413539B1 (en) * 1996-10-31 2002-07-02 Poly-Med, Inc. Hydrogel-forming, self-solvating absorbable polyester copolymers, and methods for use thereof
US7611533B2 (en) * 1995-06-07 2009-11-03 Cook Incorporated Coated implantable medical device
US6132674A (en) * 1995-10-12 2000-10-17 Bristol-Myers Squibb Company Method of making an orthopaedic implant having a porous surface
DE69724780D1 (en) * 1996-05-22 2003-10-16 Univ Ben Gurion Polysaccharide sponges for cell culture and transplantation
US6110483A (en) * 1997-06-23 2000-08-29 Sts Biopolymers, Inc. Adherent, flexible hydrogel and medicated coatings
US6179872B1 (en) * 1998-03-17 2001-01-30 Tissue Engineering Biopolymer matt for use in tissue repair and reconstruction
US6410044B1 (en) * 1998-03-19 2002-06-25 Surmodics, Inc. Crosslinkable macromers
US6548299B1 (en) * 1999-11-12 2003-04-15 Mark J. Pykett Lymphoid tissue-specific cell production from hematopoietic progenitor cells in three-dimensional devices
US6176849B1 (en) * 1999-05-21 2001-01-23 Scimed Life Systems, Inc. Hydrophilic lubricity coating for medical devices comprising a hydrophobic top coat
DE60127983D1 (en) * 2000-10-12 2007-05-31 Univ Singapore Non-intrusive, three-dimensional system for the cultivation and harvest of anchorage-dependent cells
US20050272153A1 (en) 2004-01-27 2005-12-08 Zou Xuenong Bone tissue engineering by ex vivo stem cells ongrowth into three-dimensional trabecular metal

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5282861A (en) * 1992-03-11 1994-02-01 Ultramet Open cell tantalum structures for cancellous bone implants and cell and tissue receptors

Cited By (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8491924B2 (en) 2006-04-13 2013-07-23 Case Western Reserve University Biomaterial implants
WO2007121345A3 (en) * 2006-04-13 2008-06-26 Univ Case Western Reserve Biomaterial implants
US20100021520A1 (en) * 2006-04-13 2010-01-28 Jonathan Baskin Biomaterial implants
WO2007121345A2 (en) * 2006-04-13 2007-10-25 Case Western Reserve University Biomaterial implants
US20080081362A1 (en) * 2006-09-29 2008-04-03 Daniel Keeley Multilayered Composite for Organ Augmentation and Repair
WO2008065565A3 (en) * 2006-11-30 2008-07-24 Hannes Dahnke Energy resolved imaging
US20100067771A1 (en) * 2006-11-30 2010-03-18 Koninklijke Philips Electronics N. V. Energy resolved imaging
US20100305696A1 (en) * 2007-05-24 2010-12-02 The Trustees Of Columbia University In The City Of New York Hybrid soft tissue implants from progenitor cells and biomaterials
US9199002B2 (en) * 2007-05-24 2015-12-01 The Trustees Of Columbia University In The City Of New York Hybrid soft tissue implants from progenitor cells and biomaterials
US20090275011A1 (en) * 2008-04-30 2009-11-05 Johann Eibl Sessile stem cells
US8475505B2 (en) 2008-08-13 2013-07-02 Smed-Ta/Td, Llc Orthopaedic screws
US9700431B2 (en) 2008-08-13 2017-07-11 Smed-Ta/Td, Llc Orthopaedic implant with porous structural member
US9358056B2 (en) 2008-08-13 2016-06-07 Smed-Ta/Td, Llc Orthopaedic implant
US9616205B2 (en) 2008-08-13 2017-04-11 Smed-Ta/Td, Llc Drug delivery implants
US8702767B2 (en) 2008-08-13 2014-04-22 Smed-Ta/Td, Llc Orthopaedic Screws
US9561354B2 (en) 2008-08-13 2017-02-07 Smed-Ta/Td, Llc Drug delivery implants
WO2011104657A1 (en) 2010-02-23 2011-09-01 Sheltagen Medical Ltd. Three-dimensional bone implant and method for producing same
US9265862B2 (en) 2010-02-23 2016-02-23 Sheltagen Medical Ltd. Three-dimensional bone implant and method for producing same
US20130268087A1 (en) * 2011-11-23 2013-10-10 Amendia Inc. Bone graft
US9730959B2 (en) 2011-12-29 2017-08-15 “Nextgen” Company Limited Biocomposite for regeneration of injured tissue and organs, a kit for making the biocomposite, a method of making the biocomposite and a method of treating injuries
CN104159621A (en) * 2012-01-09 2014-11-19 捷迈有限公司 Composite device that combines porous metal and bone stimuli
US8790402B2 (en) 2012-01-09 2014-07-29 Zimmer, Inc. Composite device that combines porous metal and bone stimuli
US9566156B2 (en) 2012-01-09 2017-02-14 Zimmer, Inc. Composite device that combines porous metal and bone stimuli
WO2013106318A1 (en) * 2012-01-09 2013-07-18 Zimmer, Inc. Composite device that combines porous metal and bone stimuli
CN103656752A (en) * 2012-09-25 2014-03-26 中南大学 Method for strengthening and toughening biological ceramic material by use of graphene and preparing artificial bone prepared from material

Also Published As

Publication number Publication date Type
US20140288661A1 (en) 2014-09-25 application
US20180008747A1 (en) 2018-01-11 application
US20080033548A1 (en) 2008-02-07 application
US8895046B2 (en) 2014-11-25 grant
US9795715B2 (en) 2017-10-24 grant
US20160228614A1 (en) 2016-08-11 application

Similar Documents

Publication Publication Date Title
Marcacci et al. Stem cells associated with macroporous bioceramics for long bone repair: 6-to 7-year outcome of a pilot clinical study
Habibovic et al. Osteoinductive biomaterials—properties and relevance in bone repair
Glowacki et al. Collagen scaffolds for tissue engineering
Crane et al. Bone tissue engineering
Minuth et al. Tissue engineering: generation of differentiated artificial tissues for biomedical applications
Shao et al. Evaluation of a hybrid scaffold/cell construct in repair of high-load-bearing osteochondral defects in rabbits
Liu et al. Design and development of three-dimensional scaffolds for tissue engineering
Ma et al. Engineering new bone tissue in vitro on highly porous poly (α‐hydroxyl acids)/hydroxyapatite composite scaffolds
Martin et al. Osteochondral tissue engineering
Lichte et al. Scaffolds for bone healing: concepts, materials and evidence
Sopyan et al. Porous hydroxyapatite for artificial bone applications
Barrere et al. Advanced biomaterials for skeletal tissue regeneration: Instructive and smart functions
Bueno et al. Cell-free and cell-based approaches for bone regeneration
Chen et al. Development of biodegradable porous scaffolds for tissue engineering
US5041138A (en) Neomorphogenesis of cartilage in vivo from cell culture
Marler et al. Transplantation of cells in matrices for tissue regeneration
Alhadlaq et al. Engineered adipose tissue from human mesenchymal stem cells maintains predefined shape and dimension: implications in soft tissue augmentation and reconstruction
US5904717A (en) Method and device for reconstruction of articular cartilage
Thomson et al. Biodegradable polymer scaffolds to regenerate organs
Logeart‐Avramoglou et al. Engineering bone: challenges and obstacles
Alvarez et al. Metallic scaffolds for bone regeneration
US5981825A (en) Device and methods for in vivo culturing of diverse tissue cells
Schantz et al. Repair of calvarial defects with customized tissue-engineered bone grafts I. Evaluation of osteogenesis in a three-dimensional culture system
Wu et al. Biomimetic porous scaffolds for bone tissue engineering
Bhumiratana et al. Nucleation and growth of mineralized bone matrix on silk-hydroxyapatite composite scaffolds