US20040234577A1 - Membrane for use in guided tissue regeneration - Google Patents
Membrane for use in guided tissue regeneration Download PDFInfo
- Publication number
- US20040234577A1 US20040234577A1 US10/869,909 US86990904A US2004234577A1 US 20040234577 A1 US20040234577 A1 US 20040234577A1 US 86990904 A US86990904 A US 86990904A US 2004234577 A1 US2004234577 A1 US 2004234577A1
- Authority
- US
- United States
- Prior art keywords
- membrane
- layer
- collagen
- matrix
- barrier layer
- 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
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials 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
- A61L27/38—Materials 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
- A61L27/3839—Materials 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 characterised by the site of application in the body
- A61L27/3843—Connective tissue
- A61L27/3852—Cartilage, e.g. meniscus
-
- 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
- A61F2/0077—Special surfaces of prostheses, e.g. for improving ingrowth
-
- 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
-
- 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
- A61F2/30756—Cartilage endoprostheses
-
- 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/32—Proteins, polypeptides; Degradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin
- A61L15/325—Collagen
-
- 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/40—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing ingredients of undetermined constitution or reaction products thereof, e.g. plant or animal extracts
-
- 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
- A61L27/14—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/20—Polysaccharides
-
- 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
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/24—Collagen
-
- 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
- A61L27/36—Materials 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
- A61L27/3604—Materials 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
-
- 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
- A61L27/36—Materials 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
- A61L27/38—Materials 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
- A61L27/3804—Materials 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 characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
- A61L27/3817—Cartilage-forming cells, e.g. pre-chondrocytes
-
- 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
- A61L27/36—Materials 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
- A61L27/38—Materials 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
- A61L27/3804—Materials 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 characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
- A61L27/3834—Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
-
- 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
- A61L27/36—Materials 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
- A61L27/38—Materials 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
- A61L27/3839—Materials 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 characterised by the site of application in the body
- A61L27/3843—Connective tissue
-
- 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
- A61L27/36—Materials 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
- A61L27/38—Materials 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
- A61L27/3839—Materials 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 characterised by the site of application in the body
- A61L27/3843—Connective tissue
- A61L27/3847—Bones
-
- 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
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- 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
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/005—Ingredients of undetermined constitution or reaction products thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/043—Proteins; Polypeptides; Degradation products thereof
- A61L31/044—Collagen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/146—Porous materials, e.g. foams or sponges
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/00234—Surgical instruments, devices or methods, e.g. tourniquets for minimally invasive surgery
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/00491—Surgical glue applicators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/04—Surgical instruments, devices or methods, e.g. tourniquets for suturing wounds; Holders or packages for needles or suture materials
- A61B17/06—Needles ; Sutures; Needle-suture combinations; Holders or packages for needles or suture materials
- A61B17/06166—Sutures
-
- 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
- A61F2/28—Bones
-
- 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
-
- 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
- A61F2/0077—Special surfaces of prostheses, e.g. for improving ingrowth
- A61F2002/0086—Special surfaces of prostheses, e.g. for improving ingrowth for preferentially controlling or promoting the growth of specific types of cells or tissues
-
- 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
- A61F2/0077—Special surfaces of prostheses, e.g. for improving ingrowth
- A61F2002/009—Special surfaces of prostheses, e.g. for improving ingrowth for hindering or preventing attachment of biological 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
- A61F2/28—Bones
- A61F2002/2817—Bone 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]
-
- 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
- A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
- A61F2002/30003—Material related properties of the prosthesis or of a coating on the prosthesis
- A61F2002/3006—Properties of materials and coating materials
- A61F2002/30062—(bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
-
- 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
- A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
- A61F2002/30667—Features concerning an interaction with the environment or a particular use of the prosthesis
- A61F2002/30677—Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- 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
- A61F2/30756—Cartilage endoprostheses
- A61F2002/30761—Support means for artificial cartilage, e.g. cartilage defect covering membranes
-
- 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
- A61F2/30767—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
- A61F2002/30932—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth for retarding or preventing 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
- A61F2/3094—Designing or manufacturing processes
- A61F2002/30971—Laminates, i.e. layered products
-
- 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
- A61F2/46—Special tools or methods for implanting or extracting artificial joints, accessories, bone grafts or substitutes, or particular adaptations therefor
- A61F2002/4635—Special tools or methods for implanting or extracting artificial joints, accessories, bone grafts or substitutes, or particular adaptations therefor using minimally invasive surgery
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2210/00—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2210/0004—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof bioabsorbable
-
- 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
- A61F2240/00—Manufacturing or designing of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2240/001—Designing or manufacturing processes
-
- 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
- A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
- A61F2310/00005—The prosthesis being constructed from a particular material
- A61F2310/00365—Proteins; Polypeptides; Degradation products thereof
-
- 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
- A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
- A61F2310/00389—The prosthesis being coated or covered with a particular material
- A61F2310/00976—Coating or prosthesis-covering structure made of proteins or of polypeptides, e.g. of bone morphogenic proteins BMP or of transforming growth factors TGF
- A61F2310/00982—Coating made of collagen
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/252—Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
- A61L2300/414—Growth factors
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/606—Coatings
- A61L2300/608—Coatings having two or more layers
-
- 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
- A61L2430/06—Materials or treatment for tissue regeneration for cartilage reconstruction, e.g. meniscus
Definitions
- the present invention concerns a collagen membrane implant for use in guided tissue regeneration, in particular for use in vivo in the reconstruction of bone or cartilage tissue.
- cartilage tissue such as in cartilage lesions.
- Cartilage injuries can occur in any joint though the larger joints, such as the knee and ankle, are most at risk. Such injuries can result from trauma, from degenerative conditions or osteochondritis dissecans. Cartilage injuries are a principal pathomechanical factor in the development of arthrosis. The liberation of enzymes leads to an inflammatory process of the synovia which in turn leads to abrasion of the cartilage and destruction of the joint surface.
- Recent attempts to regenerate articular cartilage in chondral defects in vivo include implantation of cultured autogenic articular chondrocytes (CACs). However, this technique has had limited success.
- CACs cultured autogenic articular chondrocytes
- WO-A-96/25961 proposes a matrix implant based on collagen II which can be implanted at the in viva site and which relies on the growth of native chondrocytes on the surface of the matrix to effect cartilage regeneration.
- the ability of such a matrix to effect complete regeneration of cartilage tissue is, however, limited.
- the invention thus provides a multi-layer membrane comprising a matrix layer predominantly of collagen II and having an open sponge-like texture, and at least one barrier layer having a close, relatively impermeable texture.
- a particular advantage of the membrane according to the invention when used is that native cells are unable to penetrate or grow into the layer having a close, relatively impermeable texture.
- a double-layer membrane in accordance with the invention which serves to shield the collagen matrix from the ingrowth of native tissue cells from one side.
- a tissue graft e.g. a periosteal graft
- a periosteal graft may initially be sutured in place such that this provides a covering over the bone or cartilage defect.
- a double-layer membrane of the invention may then be implanted at the site of the defect such that this lies in contact with the graft and may be arranged in such a way that the matrix layer faces towards the bone defect. More preferably, a double-layer membrane of the invention is initially implanted at the site of the defect with the barrier layer facing towards the bone or cartilage defect. A periosteal graft is then arranged such that this lies in contact with the matrix layer. The graft may be adhered with a biocompatible adhesive such as fibrin glue, or pinned with resorbable polylactic pins, or if necessary or possible sutured in such a way that this then serves to provide an impermeable barrier to the ingrowth of any surrounding connective tissue.
- a biocompatible adhesive such as fibrin glue, or pinned with resorbable polylactic pins, or if necessary or possible sutured in such a way that this then serves to provide an impermeable barrier to the ingrowth of any surrounding connective tissue.
- the membrane itself may be effective to prevent the ingrowth of any native tissue cells.
- the invention provides a membrane comprising at least three layers in which a matrix layer being predominantly made from collagen II and having an open sponge-like texture is provided between two barrier layers having a close, relatively impermeable texture.
- the matrix layer is capable of acting as a medium for the ingrowth of native chondrocytes thereby effecting regeneration of cartilage tissue.
- the matrix layer may be impregnated with chondrocytes either prior to or following implantation in vivo.
- the matrix layer may be impregnated with chondrocytes immediately prior to implantation, e.g. by injection, it is expected that in general the chondrocytes will be introduced into the matrix layer by direct injection of a suspension of chondrocytes following implantation. In this way, chondrocytes present in the matrix layer of the membrane are able to effect regeneration of cartilage, and ultimately new bone, whilst the membrane at the same time prevents the ingrowth of other cell types from the surrounding tissues.
- Chondrocytes for use in the invention may be obtained from cell sources which include allogenic or autogenic cells isolated from articular cartilage, periosteum and per ichondrium, and mesenchymal (stromal) stem cells from bone marrow. Since allogenic cells carry the potential for immune response and infectious complications, it is preferable to isolate the chondrocytes from autogenic cells, especially from autogenic articular cartilage. Techniques for harvesting cells are known and include enzymatic digestion or outgrowth culture. The harvested cells are then expanded in cell culture prior to reintroduction to the body. In general, at least 10 6 , preferably at least 10 7 cells should be impregnated into the matrix layer to provide for optimal regeneration of cartilage tissue.
- the matrix layer of the membrane according to the invention may contain glycosaminoglycans (GAGs) such as hyaluronic acid, chondroitin 6-sulphate, keratin sulphate, dermatan sulphate etc. which serve to provide a natural medium in which chondrocytes can become embedded and grow.
- GAGs glycosaminoglycans
- the matrix layer preferably contains from 1 to 10 wt % of glycosaminoglycans, for example 2 to 6 wt %. Although some glycosaminoglycans may be present in the impermeable layer, the greater part will be present in the matrix layer.
- GAGs occur, at least in part, as a component of proteoglycans (PGs).
- PGs proteoglycans
- the use of GAGs in the form of PGs is undesirable in view of potential immunological problems which can be caused by the protein content of the PGs.
- the matrix layer is thus substantially free from any proteoglycans. Conveniently, this may be achieved by preparing the matrix layer from a mixture of a purified telopeptide-free collagen II material and glycosaminoglycans.
- additives which may also be present in the matrix layer include, for example, chondronectin, laminin, fibronectin, calcium alginate or anchorin II to assist attachment of the chondrocytes to the collagen II fibres, and growth factors such as cartilage inducing factor (CIF), insulin-like growth factor (IGF), transforming growth factor ⁇ (TGF ⁇ ) present as homodimers or heterodimers and bone morphogenetic factors (BMP) such as native or recombinant human BMP-2, BMP-3 (osteogenin), BMP-4 and BMP-7 (OP-1, osteogenetic protein-1).
- CIF cartilage inducing factor
- IGF insulin-like growth factor
- TGF ⁇ transforming growth factor ⁇
- BMP bone morphogenetic factors
- BMP-2 affects the two pathways of bone formation independently—the direct formation of bone as well as the formation of cartilage which is then removed and replaced by bone.
- Composites of BMPs and collagen including bone matrix obtained by extraction from cortical bone from various sources or demineralised bone matrix consist of 90% collagen and 10% non-collagenous proteins (NCP) for BMP activity or for BMP/NCP induced chondrogenesis.
- NCP non-collagenous proteins
- Bone matrix-insoluble collagenous matrix and laminin or fibronectin act as carriers for BMPS.
- Some growth factors may also be present in the impermeable layer. However, the greater part will be present in the matrix layer.
- the membrane contains from 100 ⁇ g to 5 mg of growth factors.
- the membrane comprises at least two layers having different structures.
- the barrier layer of the membrane is predominantly made from collagen I and III.
- this may comprise a synthetic material, e.g. a synthetic resorbable polymer network optionally coated with a collagen material such as type I and/or type III collagen.
- suitable synthetic materials include polyesters, polyglycolic and polylactic acids (PLA) homopolymers and copolymers, glycolide and lactide copolymers, polyorthoesters and polycaprolactones. Many examples of these are openly available, e.g. from Boehringer Ingelheim in their RESOMER range. PLA polymers as wax with an appropriate molecular size of ca. 650-1200 and not too rapid a degradation are preferred.
- a particularly preferred biodegradable polymer is poly(D,L-lactic acid) in which the ratio of D-lactide to L-lactide is approx. 70:30.
- An advantage of such synthetic materials is that these can have high mechanical stability which allows the membrane implant to be stretched over complex, three dimensional bone defects without tearing. Such materials are also suitable for suturing.
- the barrier layer consists of long collagen fibres which are so closely connected that high molecular substances cannot permeate this barrier.
- the long fibres provide high tensile strength and resistance to tearing so that the material is not only a good separation membrane but can also be readily sewn. It is important in surgery that membrane implants can be sewn or pinned into position and many of the membranes which have previously been proposed do not provide this capability.
- the membrane in accordance with the invention is mechanically stable enough to be handled surgically for implantation.
- the matrix layer is very porous and may have a specific weight as low as 0.02, which permits cells very rapidly to grow into this layer.
- This layer of the membrane which normally also contains glycosaminoglycans, swells strongly and can take up as much as 5000% of liquid.
- the matrix layer should provide a pore structure (pore volume fraction and pore size) which allows cell adhesion and growth and which permits the seeded cells to maintain the chondrocytic phenotype, characterised by synthesis of cartilage-specific proteins. Pore sizes will depend on the freeze drying process used to produce the collagen II matrix but can be expected to be in the range of from 10 to 120 ⁇ m, e.g. 20 to 100 ⁇ m.
- the pore size should be around 85 ⁇ m.
- Such a pore size may readily be obtained by slow freezing at from ⁇ 5 to ⁇ 10° C. for about 24 hours followed by freeze-drying, or by adding ammonium bicarbonate to the slurry before lyophilisation.
- the matrix layer of the membrane is preferably provided by collagen II material obtained from cartilage, preferably hyaline cartilage from pigs.
- the desired thickness of the matrix layer will depend upon the nature of the bone or chondral defect to be treated, in general this can be expected to be in the range of from 2 to 10 mm, e.g. from 4 to 6 mm.
- the thickness of the barrier layer is preferably from 0.2 to 2 mm, e.g. from 0.2 to 0.7 mm.
- the barrier layer may be provided by a natural animal membrane comprising collagen I and III. Being derived from a natural source, this is totally resorbable in the body and does not form toxic degradation products. Such membranes also have particularly high tear strength in either a wet or dry state and can therefore be surgically stitched if necessary. When moist the material is very elastic which allows this to be stretched over irregularly shaped bone defects.
- Membranes providing the barrier layer of the product according to the invention include peritoneum membrane from calves or pigs which retain their natural collagen structure. Peritoneum membranes from young pigs aged 6-7 weeks old (weighing 60-80 kg) are especially preferred.
- the barrier layer should preferably comprise pure, native (not denatured) insoluble collagen and may be prepared in accordance with the method described in WO-A-95/18638.
- the natural membrane may thus first be treated with alkali, for example aqueous NaOH at a concentration of from 0.2-4% by weight. This serves to saponify any fats and also proteins which are sensitive to alkali.
- the second step is the treatment of the material with an acid, usually an inorganic acid such as HCl. This eliminates acid-sensitive contaminants.
- the material is subsequently washed until the pH is in the range 2.5-3.5.
- the membrane then has a smooth or grain side and a looser more fibrous side. It may be beneficial to effect some cross-linking of the membrane by heating to 100-120° C.
- the collagen II material used to provide the matrix layer of the membrane can be obtained from cartilage by a similar procedure to that described above in relation to the barrier layer comprising predominantly collagen I and III. It is preferable to remove water from the cartilage by treatment with acetone followed by extraction of fat with a hydrocarbon solvent such as n-hexane, though alkanols such as ethanol, ethers such as diethyl ether or chlorinated hydrocarbons such as chloroform, or mixtures thereof may be used. The defatted material is then subjected to treatment with alkali which saponifies any residual fat and degrades some of the proteins present. Finally, the material is treated with acid which effects further protein degradation. The material is allowed to swell in water and is passed through a colloid mill to produce a slurry.
- a hydrocarbon solvent such as n-hexane
- the soft slurry containing collagen II is applied to the fibrous side of the smooth membrane prepared, for example in accordance with WO-A-95/18638.
- the membrane will be placed on a smooth surface with the grain side down so that the collagen II slurry can readily be applied, e.g. by rubbing into the fibrous side of the membrane.
- the slurry thus forms a layer of any desired thickness which firmly adheres to the collagen membrane.
- the double-layer so formed is then subjected to freezing and freeze-drying to provide the desired sponge-like structure having a desired pore size. If necessary, some of the matrix layer may be removed to provide a double-membrane of uniform thickness.
- a second smooth membrane is then placed on top of the matrix layer with its fibrous side in contact with the matrix layer.
- the collagen II slurry to be applied to the membrane in general contains 1.0-4.0 weight % of the collagen, advantageously 2-3 weight %. Conveniently, the pH value of this mixture should be adjusted to 2.5-4.5, advantageously 3.0-4.0.
- the collagen II material may be cross-linked after the freeze-drying step to stabilise the matrix layer.
- This also serves to increase the mechanical stability of the matrix layer and to reduce its rate of resorption by the body.
- the degree of cross-linking should be such that the rate of degradation of the matrix matches the rate of tissue regeneration.
- cross-linking may be carried out by heating, but this must be effected carefully to avoid undesired loss of resorbability. Heating to temperatures of 100-120° C. for a period of from 30 minutes to 5 hours is preferable. More preferably, cross-linking may be effected by UV irradiation using a UV lamp e.g. for a period of up to 8 hours.
- the collagen II material advantageously contains glycosaminoglycans.
- the latter actually reacts with the collagen II to effect some cross-linking and produces an insoluble product. If necessary, further cross-linking can be effected by heating the material or by UV irradiation as discussed above.
- the reaction between the glycosaminoglycans and the collagen can be effected at ambient temperatures at a pH in the range 2.5-3.5.
- the quantity of glycosaminoglycan may be between 1 and 10% by weight.
- the material may be subjected to freezing and freeze-drying immediately after such treatment.
- slurry formation may be effected by raising the pH of the collagen II mass.
- the mass is cooled to about 4° C. and the pH value slowly raised by addition of cold aqueous NaOH at 4° C. up to a pH value 6.5-7.5.
- the mass is held at ambient temperature for 15-25 hours. In this time, the slurry is formed and after slurry formation, the mass can be frozen and freeze-dried.
- a still further alternative is to neutralise the collagen II mass to a pH value 6.8-7.4, subsequent to removal of air.
- the mixture is placed in the mould and incubated for 15-20 hours at 37° C. A fine slurry develops which can subsequently be frozen and freeze-dried.
- the material After the application of the slurry to the membrane, the material is frozen. In order to obtain a reproducible pore size, the freezing must be carefully controlled and the rate and time of freezing, the pH value and the particle size must be accurately controlled. In order to obtain very small pores, the material may be shock frozen at very low temperature.
- the frozen membrane is then freeze-dried and subsequently heated to 110-130° C. In this way, some cross-linking is effected. Subsequently, the freeze-dried biomembrane may be adjusted to the required thickness so that the thickness of the matrix layer is commonly about 2 mm.
- the double membrane is then sterilised, for example by gamma-irradiation or with ethyleneoxide. Sterilisation by strong irradiation e.g. with 60 Co in doses of 25 kGy may deactivate the BMPs. In such circumstances, the sterile matrix may be impregnated with BMPs in sterile saline prior to implantation.
- the membrane according to the invention can be used in medicine in the following ways:
- the invention also provides the use of a multi-layer collagen membrane as described above in guided tissue regeneration.
- the collagen II content of the membrane is particularly suitable for regeneration of cartilage tissue but is also suitable for other tissue types.
- the invention thus provides a membrane as hereinbefore described for use as a guided tissue regeneration implant.
- the invention further provides a method of treating a bone or cartilage defect in the human or non-human animal body, said method comprising application of a membrane as hereinbefore described to the defect, said membrane being oriented such that the barrier layer prevents the ingrowth of undesirable tissue types into the area of bone or cartilage regeneration.
- the material was ground three times in a homogenizer.
- the optical particle size at the end of size reduction was about 8 mm.
- the cartilage pieces were dewatered by washing 4 times with acetone, each time for 8 hours.
- the cartilage was then defatted by extraction 4 times with n-hexane. Each treatment lasted at least 8 hours.
- the ratio of hexane to cartilage was 1:10.
- the material was then treated with NaOH (5% by weight) whereby the ratio of cartilage to liquid was 1:4 and the treatment time was 32 hours.
- the pieces of cartilage were well stirred.
- the alkali was washed from the cartilage.
- the original pH of 14 was thereby reduced to 9-11.
- the dissolved impurities were washed out and separated from the cartilage.
- the liquid resulting from the alkaline treatment was collected for the recovery of glycosaminoglycan.
- the collagen material was then treated with strong HCl (about 3% by weight) initially at a pH value under 1.0.
- the treatment time was 4-6 hours.
- the material was washed with cold water long enough for the pH value to rise to 3-3.5. All impurities were removed and the product was a salt-free collagen mass, suitable for production of a sponge or other collagen material.
- the cartilage mass may be, according to the intended result, degassed, frozen and freeze-dried.
- the extract resulting from alkaline treatment above contained glycosaminoglycan, alkali, denatured proteins and salts.
- the extract was firstly neutralised with HCl, the pH value after neutralisation being 6.
- the extract was then treated with a filter aid, namely kieselguhr, which had the effect of removing the denatured proteins.
- a filter aid namely kieselguhr, which had the effect of removing the denatured proteins.
- 0.5 weight percent of kieselguhr was introduced into the extract and removed by filtration together with the denatured protein.
- glycosaminoglycan solution so obtained was admixed with collagen material from above to provide a collagen II matrix containing glycosaminoglycan.
- the collagen II mass had the following properties:
- GAG 3 weight % (calculated on the basis of collagen)
- freeze-drying time 14 hours.
- the collagen II matrix layer was subsequently split to a thickness of 1 mm.
- Example 1(A) The freshly prepared peritoneum membrane from Example 1(A) was applied to a glass plate and the thick collagen II mass, having the properties as in Example 1, was rubbed into the membrane. 50 g of the collagen II mass was diluted to 100 ml with distilled water and thoroughly stirred. During the stirring, 100 ml of glycosaminoglycan solution was slowly added. Collagen was precipitated in the form of a mass together with GAG. After the precipitation, the mass was homogenised and the dispersion so obtained was applied to the membrane. A slurry formed overnight and the treated membrane was further processed as described in Example 1.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Medicinal Chemistry (AREA)
- Dermatology (AREA)
- Vascular Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cell Biology (AREA)
- Zoology (AREA)
- Botany (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Surgery (AREA)
- Cardiology (AREA)
- Molecular Biology (AREA)
- Materials Engineering (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Dispersion Chemistry (AREA)
- Biophysics (AREA)
- Developmental Biology & Embryology (AREA)
- Materials For Medical Uses (AREA)
- Prostheses (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Polarising Elements (AREA)
- External Artificial Organs (AREA)
- Laminated Bodies (AREA)
Abstract
The invention provides a multi-layer membrane comprising a matrix layer predominantly of collagen II and having an open sponge-like texture, and at least one barrier layer having a close, relatively impermeable texture. Such a membrane is particularly suitable for use in guided tissue regeneration, in particular for use in vivo in the reconstruction of bone or cartilage tissue.
Description
- The present invention concerns a collagen membrane implant for use in guided tissue regeneration, in particular for use in vivo in the reconstruction of bone or cartilage tissue.
- In tissue regeneration, it has long proved difficult to reconstruct cartilage tissue, such as in cartilage lesions. Cartilage injuries can occur in any joint though the larger joints, such as the knee and ankle, are most at risk. Such injuries can result from trauma, from degenerative conditions or osteochondritis dissecans. Cartilage injuries are a principal pathomechanical factor in the development of arthrosis. The liberation of enzymes leads to an inflammatory process of the synovia which in turn leads to abrasion of the cartilage and destruction of the joint surface. Recent attempts to regenerate articular cartilage in chondral defects in vivo include implantation of cultured autogenic articular chondrocytes (CACs). However, this technique has had limited success.
- It is now generally accepted that reconstruction of tissue requires the provision of a matrix to serve as a guide for cells, which grow along and between the fibres of the matrix. More recently, the use of CACs seeded in both synthetic and natural resorbable matrices has been proposed. However, attempts to reconstruct cartilage tissue using matrices based on polylactic acid, polyglycolic acid and collagen I or III, have required the matrices to be loaded in vitro with chondrocytes prior to implantation. This gives rise to complications in terms of the sterile culture of the chondrocytes i.e. immunological inflammatory reactions by giant cells and fibroblastic cells at the interface between implants and tissue.
- WO-A-96/25961 proposes a matrix implant based on collagen II which can be implanted at the in viva site and which relies on the growth of native chondrocytes on the surface of the matrix to effect cartilage regeneration. The ability of such a matrix to effect complete regeneration of cartilage tissue is, however, limited.
- There is thus a need for a matrix implant which will permit successful ingrowth of native chondrocytes and thus regeneration of cartilage tissue following implantation in vivo. We have now found that cartilage, and ultimately new bone tissue, can be reconstructed by the use of a cbllagen II matrix which in vivo is shielded not only from the surrounding connective tissue but also from the underlying bone or cartilage defect. It is envisaged that this may be achieved through the use of a multi-layer membrane implant which itself is capable of preventing the undesired ingrowth of any surrounding tissues into the matrix, or which may be surgically implanted at the site of the defect so as to achieve this effect.
- Viewed from one aspect the invention thus provides a multi-layer membrane comprising a matrix layer predominantly of collagen II and having an open sponge-like texture, and at least one barrier layer having a close, relatively impermeable texture.
- A particular advantage of the membrane according to the invention when used is that native cells are unable to penetrate or grow into the layer having a close, relatively impermeable texture.
- Whilst not wishing to be bound by theory, it is now believed that successful cartilage regeneration requires that the rapid ingrowth not only of native tissue cells, such as connective tissues, blood vessels etc., but also of any new bone tissue into the site of the defect be prevented. This may be achieved using a double-layer membrane in accordance with the invention which serves to shield the collagen matrix from the ingrowth of native tissue cells from one side. During surgical implantation this may be used in combination with a tissue graft, e.g. a periosteal graft, effective to prevent the ingrowth of native tissue cells from the opposing side. Thus, for example, a periosteal graft may initially be sutured in place such that this provides a covering over the bone or cartilage defect. A double-layer membrane of the invention may then be implanted at the site of the defect such that this lies in contact with the graft and may be arranged in such a way that the matrix layer faces towards the bone defect. More preferably, a double-layer membrane of the invention is initially implanted at the site of the defect with the barrier layer facing towards the bone or cartilage defect. A periosteal graft is then arranged such that this lies in contact with the matrix layer. The graft may be adhered with a biocompatible adhesive such as fibrin glue, or pinned with resorbable polylactic pins, or if necessary or possible sutured in such a way that this then serves to provide an impermeable barrier to the ingrowth of any surrounding connective tissue.
- In an alternative embodiment of the invention, the membrane. itself may be effective to prevent the ingrowth of any native tissue cells. Thus, viewed from a further aspect the invention provides a membrane comprising at least three layers in which a matrix layer being predominantly made from collagen II and having an open sponge-like texture is provided between two barrier layers having a close, relatively impermeable texture.
- The matrix layer is capable of acting as a medium for the ingrowth of native chondrocytes thereby effecting regeneration of cartilage tissue. However, to further aid in regenerating cartilage tissue the matrix layer may be impregnated with chondrocytes either prior to or following implantation in vivo. Whilst the matrix layer may be impregnated with chondrocytes immediately prior to implantation, e.g. by injection, it is expected that in general the chondrocytes will be introduced into the matrix layer by direct injection of a suspension of chondrocytes following implantation. In this way, chondrocytes present in the matrix layer of the membrane are able to effect regeneration of cartilage, and ultimately new bone, whilst the membrane at the same time prevents the ingrowth of other cell types from the surrounding tissues.
- Chondrocytes for use in the invention may be obtained from cell sources which include allogenic or autogenic cells isolated from articular cartilage, periosteum and per ichondrium, and mesenchymal (stromal) stem cells from bone marrow. Since allogenic cells carry the potential for immune response and infectious complications, it is preferable to isolate the chondrocytes from autogenic cells, especially from autogenic articular cartilage. Techniques for harvesting cells are known and include enzymatic digestion or outgrowth culture. The harvested cells are then expanded in cell culture prior to reintroduction to the body. In general, at least 106, preferably at least 107 cells should be impregnated into the matrix layer to provide for optimal regeneration of cartilage tissue.
- In general, it is desirable for the matrix layer of the membrane according to the invention to contain glycosaminoglycans (GAGs) such as hyaluronic acid, chondroitin 6-sulphate, keratin sulphate, dermatan sulphate etc. which serve to provide a natural medium in which chondrocytes can become embedded and grow. Whilst it is possible to incorporate into the collagen matrix glycosaminoglycans from different sources which do not necessarily have the same composition, molecular weight and physiological properties as those from cartilage, preferred glycosaminoglycans are those extracted from cartilage itself. In general, the matrix layer preferably contains from 1 to 10 wt % of glycosaminoglycans, for example 2 to 6 wt %. Although some glycosaminoglycans may be present in the impermeable layer, the greater part will be present in the matrix layer.
- In native collagen tissues GAGs occur, at least in part, as a component of proteoglycans (PGs). The use of GAGs in the form of PGs is undesirable in view of potential immunological problems which can be caused by the protein content of the PGs. Preferably, the matrix layer is thus substantially free from any proteoglycans. Conveniently, this may be achieved by preparing the matrix layer from a mixture of a purified telopeptide-free collagen II material and glycosaminoglycans.
- Other additives which may also be present in the matrix layer include, for example, chondronectin, laminin, fibronectin, calcium alginate or anchorin II to assist attachment of the chondrocytes to the collagen II fibres, and growth factors such as cartilage inducing factor (CIF), insulin-like growth factor (IGF), transforming growth factor β (TGFβ) present as homodimers or heterodimers and bone morphogenetic factors (BMP) such as native or recombinant human BMP-2, BMP-3 (osteogenin), BMP-4 and BMP-7 (OP-1, osteogenetic protein-1). BMP-2 affects the two pathways of bone formation independently—the direct formation of bone as well as the formation of cartilage which is then removed and replaced by bone. Composites of BMPs and collagen including bone matrix obtained by extraction from cortical bone from various sources or demineralised bone matrix consist of 90% collagen and 10% non-collagenous proteins (NCP) for BMP activity or for BMP/NCP induced chondrogenesis. Bone matrix-insoluble collagenous matrix and laminin or fibronectin act as carriers for BMPS. Some growth factors may also be present in the impermeable layer. However, the greater part will be present in the matrix layer. In general, the membrane contains from 100 μg to 5 mg of growth factors.
- As indicated above, the membrane comprises at least two layers having different structures. Preferably, the barrier layer of the membrane is predominantly made from collagen I and III. Alternatively, this may comprise a synthetic material, e.g. a synthetic resorbable polymer network optionally coated with a collagen material such as type I and/or type III collagen.
- Examples of suitable synthetic materials include polyesters, polyglycolic and polylactic acids (PLA) homopolymers and copolymers, glycolide and lactide copolymers, polyorthoesters and polycaprolactones. Many examples of these are openly available, e.g. from Boehringer Ingelheim in their RESOMER range. PLA polymers as wax with an appropriate molecular size of ca. 650-1200 and not too rapid a degradation are preferred. A particularly preferred biodegradable polymer is poly(D,L-lactic acid) in which the ratio of D-lactide to L-lactide is approx. 70:30. An advantage of such synthetic materials is that these can have high mechanical stability which allows the membrane implant to be stretched over complex, three dimensional bone defects without tearing. Such materials are also suitable for suturing.
- Advantageously, the barrier layer consists of long collagen fibres which are so closely connected that high molecular substances cannot permeate this barrier. The long fibres provide high tensile strength and resistance to tearing so that the material is not only a good separation membrane but can also be readily sewn. It is important in surgery that membrane implants can be sewn or pinned into position and many of the membranes which have previously been proposed do not provide this capability. The membrane in accordance with the invention is mechanically stable enough to be handled surgically for implantation.
- The matrix layer is very porous and may have a specific weight as low as 0.02, which permits cells very rapidly to grow into this layer. This layer of the membrane, which normally also contains glycosaminoglycans, swells strongly and can take up as much as 5000% of liquid. Ideally, the matrix layer should provide a pore structure (pore volume fraction and pore size) which allows cell adhesion and growth and which permits the seeded cells to maintain the chondrocytic phenotype, characterised by synthesis of cartilage-specific proteins. Pore sizes will depend on the freeze drying process used to produce the collagen II matrix but can be expected to be in the range of from 10 to 120 μm, e.g. 20 to 100 μm. Optionally the pore size should be around 85 μm. Such a pore size may readily be obtained by slow freezing at from −5 to −10° C. for about 24 hours followed by freeze-drying, or by adding ammonium bicarbonate to the slurry before lyophilisation.
- The matrix layer of the membrane is preferably provided by collagen II material obtained from cartilage, preferably hyaline cartilage from pigs.
- Whilst the desired thickness of the matrix layer will depend upon the nature of the bone or chondral defect to be treated, in general this can be expected to be in the range of from 2 to 10 mm, e.g. from 4 to 6 mm. The thickness of the barrier layer is preferably from 0.2 to 2 mm, e.g. from 0.2 to 0.7 mm.
- The barrier layer may be provided by a natural animal membrane comprising collagen I and III. Being derived from a natural source, this is totally resorbable in the body and does not form toxic degradation products. Such membranes also have particularly high tear strength in either a wet or dry state and can therefore be surgically stitched if necessary. When moist the material is very elastic which allows this to be stretched over irregularly shaped bone defects.
- Besides collagen, natural animal membranes contain many other biomaterials, which must be removed. It is known to treat such membranes with enzymes, solvents or other chemicals to effect purification and to use these membranes in medicine. Most of these materials are too thin and very often not particularly easy to use. The collagen fibrils have lost their native character and further disadvantages are that the material often has insufficient strength for use as a sewable material, has no water-swelling properties and provides no difference between the smooth grain side and the fibrous flesh side. The fibrous form of purified telopeptide-free collagen Type I or II, being less soluble and biodegradable, has been found to provide the most advantageous carrier material.
- Membranes providing the barrier layer of the product according to the invention include peritoneum membrane from calves or pigs which retain their natural collagen structure. Peritoneum membranes from young pigs aged 6-7 weeks old (weighing 60-80 kg) are especially preferred.
- The barrier layer should preferably comprise pure, native (not denatured) insoluble collagen and may be prepared in accordance with the method described in WO-A-95/18638. The natural membrane may thus first be treated with alkali, for example aqueous NaOH at a concentration of from 0.2-4% by weight. This serves to saponify any fats and also proteins which are sensitive to alkali. The second step is the treatment of the material with an acid, usually an inorganic acid such as HCl. This eliminates acid-sensitive contaminants. The material is subsequently washed until the pH is in the range 2.5-3.5. The membrane then has a smooth or grain side and a looser more fibrous side. It may be beneficial to effect some cross-linking of the membrane by heating to 100-120° C.
- The collagen II material used to provide the matrix layer of the membrane can be obtained from cartilage by a similar procedure to that described above in relation to the barrier layer comprising predominantly collagen I and III. It is preferable to remove water from the cartilage by treatment with acetone followed by extraction of fat with a hydrocarbon solvent such as n-hexane, though alkanols such as ethanol, ethers such as diethyl ether or chlorinated hydrocarbons such as chloroform, or mixtures thereof may be used. The defatted material is then subjected to treatment with alkali which saponifies any residual fat and degrades some of the proteins present. Finally, the material is treated with acid which effects further protein degradation. The material is allowed to swell in water and is passed through a colloid mill to produce a slurry.
- To produce the multi-layer membrane, the soft slurry containing collagen II is applied to the fibrous side of the smooth membrane prepared, for example in accordance with WO-A-95/18638. Normally, the membrane will be placed on a smooth surface with the grain side down so that the collagen II slurry can readily be applied, e.g. by rubbing into the fibrous side of the membrane. The slurry thus forms a layer of any desired thickness which firmly adheres to the collagen membrane. The double-layer so formed is then subjected to freezing and freeze-drying to provide the desired sponge-like structure having a desired pore size. If necessary, some of the matrix layer may be removed to provide a double-membrane of uniform thickness. To produce a three-layer membrane, a second smooth membrane is then placed on top of the matrix layer with its fibrous side in contact with the matrix layer.
- The collagen II slurry to be applied to the membrane in general contains 1.0-4.0 weight % of the collagen, advantageously 2-3 weight %. Conveniently, the pH value of this mixture should be adjusted to 2.5-4.5, advantageously 3.0-4.0.
- Advantageously, the collagen II material may be cross-linked after the freeze-drying step to stabilise the matrix layer. This also serves to increase the mechanical stability of the matrix layer and to reduce its rate of resorption by the body. Ideally, the degree of cross-linking should be such that the rate of degradation of the matrix matches the rate of tissue regeneration. Physically, cross-linking may be carried out by heating, but this must be effected carefully to avoid undesired loss of resorbability. Heating to temperatures of 100-120° C. for a period of from 30 minutes to 5 hours is preferable. More preferably, cross-linking may be effected by UV irradiation using a UV lamp e.g. for a period of up to 8 hours.
- The collagen II material advantageously contains glycosaminoglycans. The latter actually reacts with the collagen II to effect some cross-linking and produces an insoluble product. If necessary, further cross-linking can be effected by heating the material or by UV irradiation as discussed above. The reaction between the glycosaminoglycans and the collagen can be effected at ambient temperatures at a pH in the range 2.5-3.5. The quantity of glycosaminoglycan may be between 1 and 10% by weight. The material may be subjected to freezing and freeze-drying immediately after such treatment.
- Alternatively, slurry formation may be effected by raising the pH of the collagen II mass. In this procedure, the mass is cooled to about 4° C. and the pH value slowly raised by addition of cold aqueous NaOH at 4° C. up to a pH value 6.5-7.5. Subsequently, the mass is held at ambient temperature for 15-25 hours. In this time, the slurry is formed and after slurry formation, the mass can be frozen and freeze-dried.
- A still further alternative is to neutralise the collagen II mass to a pH value 6.8-7.4, subsequent to removal of air. The mixture is placed in the mould and incubated for 15-20 hours at 37° C. A fine slurry develops which can subsequently be frozen and freeze-dried.
- Which of the above three methods is used depends upon the properties of the desired product. The first process gives the most stable product. However, the precipitation may give clumps of material and must be very carefully carried out. The second method gives a soft and uniform product which is, however, more soluble than the product of the first process.
- In the production of the slurry, it is possible to additionally introduce further desirable substances such as medicines, e.g. antibacterials such as taurolidine or antibiotics such as gentamycin.
- After the application of the slurry to the membrane, the material is frozen. In order to obtain a reproducible pore size, the freezing must be carefully controlled and the rate and time of freezing, the pH value and the particle size must be accurately controlled. In order to obtain very small pores, the material may be shock frozen at very low temperature.
- The frozen membrane is then freeze-dried and subsequently heated to 110-130° C. In this way, some cross-linking is effected. Subsequently, the freeze-dried biomembrane may be adjusted to the required thickness so that the thickness of the matrix layer is commonly about 2 mm. The double membrane is then sterilised, for example by gamma-irradiation or with ethyleneoxide. Sterilisation by strong irradiation e.g. with60Co in doses of 25 kGy may deactivate the BMPs. In such circumstances, the sterile matrix may be impregnated with BMPs in sterile saline prior to implantation.
- The membrane according to the invention can be used in medicine in the following ways:
- As a material for guided tissue regeneration. Cell growth is encouraged by the matrix layer. The barrier layer inhibits undesired cell growth.
- As a material for the repair of chondral defects, i.e. lesions which do not penetrate the subchondral plate, and in the repair of osteochondral defects.
- The invention also provides the use of a multi-layer collagen membrane as described above in guided tissue regeneration. The collagen II content of the membrane is particularly suitable for regeneration of cartilage tissue but is also suitable for other tissue types.
- Viewed from a further aspect the invention thus provides a membrane as hereinbefore described for use as a guided tissue regeneration implant.
- The invention further provides a method of treating a bone or cartilage defect in the human or non-human animal body, said method comprising application of a membrane as hereinbefore described to the defect, said membrane being oriented such that the barrier layer prevents the ingrowth of undesirable tissue types into the area of bone or cartilage regeneration.
- The following examples are given by way of illustration only. In the Examples, all steps have to be performed under aseptic conditions in, for example, Clean Rooms.
- (A) Peritoneal membranes from young calves are completely freed from flesh and grease by mechanical means, washed under running water and treated with 2% NaOH solution for twelve hours. The membranes are then washed under running water and acidified with 0.5% HCl. After the material has been acidified through its entire thickness (about three hours) the material is washed until a pH of 3.5 is obtained. The material is then shrunk with 7% saline solution, neutralised with 1% NaHCO3 solution and washed under running water. The material is then dehydrated with acetone and degreased with n-hexane.
- (B) Frozen cartilage from freshly slaughtered pigs was steeped in cold water, thoroughly washed through and mechanically purified from flesh residues, bones and hard pieces. Subsequently, the material was washed for 30 minutes under flowing water.
- Subsequently, the material was ground three times in a homogenizer. The optical particle size at the end of size reduction was about 8 mm.
- The cartilage pieces were dewatered by washing 4 times with acetone, each time for 8 hours. The cartilage was then defatted by extraction 4 times with n-hexane. Each treatment lasted at least 8 hours. The ratio of hexane to cartilage was 1:10.
- After defatting, the cartilage was swelled in drinking water. The ratio of water:material was 10:1. The treatment time was 24 hours.
- The material was then treated with NaOH (5% by weight) whereby the ratio of cartilage to liquid was 1:4 and the treatment time was 32 hours. During the treatment, the pieces of cartilage were well stirred. Subsequently, the alkali was washed from the cartilage. The original pH of 14 was thereby reduced to 9-11. The dissolved impurities were washed out and separated from the cartilage. The liquid resulting from the alkaline treatment was collected for the recovery of glycosaminoglycan.
- The collagen material was then treated with strong HCl (about 3% by weight) initially at a pH value under 1.0. The treatment time was 4-6 hours.
- Subsequently, the material was washed with cold water long enough for the pH value to rise to 3-3.5. All impurities were removed and the product was a salt-free collagen mass, suitable for production of a sponge or other collagen material. For that purpose, the cartilage mass may be, according to the intended result, degassed, frozen and freeze-dried.
- The extract resulting from alkaline treatment above contained glycosaminoglycan, alkali, denatured proteins and salts. The extract was firstly neutralised with HCl, the pH value after neutralisation being 6. The extract was then treated with a filter aid, namely kieselguhr, which had the effect of removing the denatured proteins. 0.5 weight percent of kieselguhr was introduced into the extract and removed by filtration together with the denatured protein.
- The supernatant was then submitted to ultrafiltration using a membrane having a molecular weight cut off at about 10,000 daltons. In this way, salts were removed to leave purified glycosaminoglycan.
- The glycosaminoglycan solution so obtained was admixed with collagen material from above to provide a collagen II matrix containing glycosaminoglycan.
- The collagen II mass had the following properties:
- TG=2.8 weight %
- GAG=3 weight % (calculated on the basis of collagen)
- pH value 3.5
- (C) The freshly prepared peritoneum membrane prepared as in (A) above was uniformly soaked in water and laid flat on a glass plate with the fibrous side upwards. Subsequently, the membrane was thoroughly wetted with the collagen II mass prepared as in (B) above. The membrane was stretched flat in all directions so as to remain adhered to the plate. The collagen II mass was thereby rubbed into the membrane.
- The very thick mass was applied to the membrane and the plate was left overnight in the refrigerator at a temperature of about 4° C. In that period a slurry was formed.
- The slurry was frozen under the following conditions:
Temperature of the bath −12° C. Time 40 minutes - Subsequently, the frozen slurry was freeze-dried and then warmed to 125° C.
Freeze-drying time = 14 hours. - The collagen II matrix layer was subsequently split to a thickness of 1 mm.
- The freshly prepared peritoneum membrane from Example 1(A) was applied to a glass plate and the thick collagen II mass, having the properties as in Example 1, was rubbed into the membrane. 50 g of the collagen II mass was diluted to 100 ml with distilled water and thoroughly stirred. During the stirring, 100 ml of glycosaminoglycan solution was slowly added. Collagen was precipitated in the form of a mass together with GAG. After the precipitation, the mass was homogenised and the dispersion so obtained was applied to the membrane. A slurry formed overnight and the treated membrane was further processed as described in Example 1.
Claims (20)
1. A membrane comprising a resorbable multi-layer membrane for use in vivo in the reconstruction of bone or cartilage tissue, said resorbable multi-layer membrane comprising a matrix layer having a matrix consisting essentially of collagen II and having an open sponge-like texture, and at least one barrier layer having a close, relatively impermeable texture, the at least one barrier layer consisting essentially of a barrier layer material selected from the group consisting of collagen I, collagen III and a mixture thereof, wherein said multi-layer membrane is formed by adhering of said matrix layer to said at least one barrier layer by non-sutured adhesive, so that said matrix layer is adhered firmly to and in direct contact with said at least one barrier layer.
2. A membrane as claimed in claim 1 in which the matrix layer is provided between two barrier layers.
3. A membrane as claimed in claim 1 in which the matrix layer is provided by collagen II material derived from natural cartilage.
4. A membrane as claimed in claim 3 wherein the collagen II material is derived from hyaline cartilage from pigs.
5. A membrane as claimed in claim 3 in which the collagen II material is physically cross-linked.
6. A membrane as claimed in claim 4 in which the at least one barrier layer is derived from peritoneum membrane from calves or pigs.
7. A membrane as claimed in claim 1 in which the matrix layer is impregnated with chondrocytes isolated from articular cartilage, periosteum, periocardium or mesenchymal stem cells from bone marrow.
8. A membrane as claimed in claim 1 in which the matrix layer, said at least one barrier layer, or each said layer is impregnated with a glycosaminoglycan.
9. A membrane as claimed in claim 8 wherein the glycosaminoglycan is hyaluronic acid, chondroitin 6-sulphate, keratin sulphate or dermatan sulphate.
10. A membrane as claimed in claim 1 in which the matrix and barrier layers are substantially free from proteoglycans.
11. A membrane as claimed in claim 1 in which the matrix layer, said at least one barrier layer, or each of the layers further comprise chondronectin, lectin, fibronectin, calcium alginate, anchorin II, growth factors or bone morphogenetic factors.
12. A process for the preparation of a membrane as claimed in claim 1 in which a collagen II slurry is applied to a surface of a barrier membrane having a close, relatively impermeable texture, followed by freeze-drying whereby to provide a matrix layer having an open sponge-like structure.
13. A method of treating a bone or cartilage defect in the human or non-human animal body, said method comprising application of a membrane as claimed in claim 1 to the defect, said membrane being oriented such that the barrier layer or layers prevent the ingrowth of undesirable tissue types into the area of bone or cartilage regeneration.
14. A method of treating a bone or cartilage defect in the human or non-human animal body, said method comprising application of a membrane as claimed in claim 1 to the defect, said membrane being oriented such that the barrier layer or layers prevent the ingrowth of undesirable tissue types into the area of bone or cartilage regeneration, and wherein the matrix layer of said membrane is impregnated with chondrocytes either immediately prior to or following application to the defect.
15. The method of claim 13 wherein said membrane is applied during arthroscopic surgery.
16. The method of claim 14 wherein said membrane is applied during arthroscopic surgery.
17. A membrane as claimed in claim 11 wherein the growth factors are cartilage inducing factor (CTF), insulin-like growth factor (IGF), or transforming growth factor (TGF ).
18. A membrane as claimed in claim 11 wherein the bone morphogenetic factors are human BMP-2, BMP-3, BMP-4 or BMP-7.
19. A membrane comprising a resorbable multi-layer membrane for use in vivo in the reconstruction of bone or cartilage tissue at a site of a defect in said tissue, said resorbable multi-layer membrane comprising a matrix layer having a matrix comprising collagen I, collagen III or a mixture thereof, and having an open sponge-like texture, and at least one barrier layer having a close, relatively impermeable texture, the at least one barrier layer comprising a barrier layer comprising collagen I, collagen III or a mixture thereof, wherein said multi-layer membrane is formed by application of said matrix layer to said at least one barrier layer as a slurry, so that said matrix layer is adhered firmly to and in direct contact with said at least one barrier layer, wherein firm adherence of the matrix layer to said at least one barrier layer results essentially solely from application of said slurry to said at least one barrier layer.
20. A membrane comprising a resorbable multi-layer membrane for use in vivo in the reconstruction of bone or cartilage tissue at a site of a defect in said tissue, said resorbable multi-layer membrane comprising a matrix layer having a matrix comprising collagen I, collagen II or a mixture thereof, and having an open sponge-like texture, and at least one barrier layer having a close, relatively impermeable texture, the at least one barrier layer comprising collagen I, collagen III or a mixture thereof, wherein said multi-layer membrane is formed by application of said matrix layer to said at least one barrier layer by non-sutured adhesive, so that said matrix layer is adhered firmly to and in direct contact with said at least one barrier layer.
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/869,909 US20040234577A1 (en) | 1997-10-10 | 2004-06-18 | Membrane for use in guided tissue regeneration |
US11/046,897 US20050186283A1 (en) | 1997-10-10 | 2005-02-01 | Collagen carrier of therapeutic genetic material, and method |
US11/046,898 US20050186673A1 (en) | 1995-02-22 | 2005-02-01 | Collagen carrier of therapeutic genetic material, and method |
US11/317,247 US8858981B2 (en) | 1997-10-10 | 2005-12-27 | Bone healing material comprising matrix carrying bone-forming cells |
US11/509,826 US9034315B2 (en) | 1997-10-10 | 2006-08-25 | Cell-charged multi-layer collagen membrane |
US11/928,384 US8911763B2 (en) | 1997-10-10 | 2007-10-30 | Collagen carrier of therapeutic genetic material and method |
US11/928,387 US20080268053A1 (en) | 1995-02-22 | 2007-10-30 | Collagen carrier of therapeutic genetic material, and method |
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB9721585.9 | 1997-10-10 | ||
GBGB9721585.9A GB9721585D0 (en) | 1997-10-10 | 1997-10-10 | Chemical product |
PCT/GB1998/002976 WO1999019005A1 (en) | 1997-10-10 | 1998-10-05 | Membrane for use in guided tissue regeneration |
US09/545,465 US6752834B2 (en) | 1997-10-10 | 2000-04-07 | Membrane for in guided tissue regeneration |
US10/869,909 US20040234577A1 (en) | 1997-10-10 | 2004-06-18 | Membrane for use in guided tissue regeneration |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/545,465 Continuation US6752834B2 (en) | 1995-02-22 | 2000-04-07 | Membrane for in guided tissue regeneration |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/046,897 Continuation-In-Part US20050186283A1 (en) | 1997-10-10 | 2005-02-01 | Collagen carrier of therapeutic genetic material, and method |
US11/046,898 Continuation-In-Part US20050186673A1 (en) | 1995-02-22 | 2005-02-01 | Collagen carrier of therapeutic genetic material, and method |
Publications (1)
Publication Number | Publication Date |
---|---|
US20040234577A1 true US20040234577A1 (en) | 2004-11-25 |
Family
ID=10820405
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/545,465 Expired - Fee Related US6752834B2 (en) | 1995-02-22 | 2000-04-07 | Membrane for in guided tissue regeneration |
US10/869,909 Abandoned US20040234577A1 (en) | 1995-02-22 | 2004-06-18 | Membrane for use in guided tissue regeneration |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/545,465 Expired - Fee Related US6752834B2 (en) | 1995-02-22 | 2000-04-07 | Membrane for in guided tissue regeneration |
Country Status (14)
Country | Link |
---|---|
US (2) | US6752834B2 (en) |
EP (1) | EP1023091B1 (en) |
JP (1) | JP4819995B2 (en) |
CN (1) | CN1181893C (en) |
AT (1) | ATE286409T1 (en) |
CA (1) | CA2305740C (en) |
CZ (1) | CZ297205B6 (en) |
DE (1) | DE69828519T2 (en) |
DK (1) | DK1023091T3 (en) |
ES (1) | ES2236936T3 (en) |
GB (1) | GB9721585D0 (en) |
PL (1) | PL191497B1 (en) |
RU (1) | RU2217171C2 (en) |
WO (1) | WO1999019005A1 (en) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20080260801A1 (en) * | 2005-11-17 | 2008-10-23 | Gelita Ag | Composite material, especially for medical use, and method for producing the material |
WO2011091796A1 (en) * | 2010-01-27 | 2011-08-04 | UroTec GmbH | Tissue graft structure that can be sutured for reconstructing a human or animal organ |
WO2014010859A1 (en) * | 2012-07-09 | 2014-01-16 | 주식회사 오스코텍 | Production method for absorbent barrier membrane for inducing tissue regeneration |
CN107405422A (en) * | 2015-03-18 | 2017-11-28 | 富士胶片株式会社 | Regenerating bone or cartilage material and its manufacture method |
US11241518B2 (en) | 2015-03-18 | 2022-02-08 | Fujifilm Corporation | Cartilage regenerative material |
Families Citing this family (154)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050186673A1 (en) * | 1995-02-22 | 2005-08-25 | Ed. Geistlich Soehne Ag Fuer Chemistrie Industrie | Collagen carrier of therapeutic genetic material, and method |
US20030039695A1 (en) * | 2001-08-10 | 2003-02-27 | Ed. Geistlich Soehne Ag Fuer Chemische Industrie | Collagen carrier of therapeutic genetic material, and method |
GB9721585D0 (en) * | 1997-10-10 | 1997-12-10 | Geistlich Soehne Ag | Chemical product |
GB9503492D0 (en) | 1995-02-22 | 1995-04-12 | Ed Geistlich S Hne A G F R Che | Chemical product |
US6569172B2 (en) | 1996-08-30 | 2003-05-27 | Verigen Transplantation Service International (Vtsi) | Method, instruments, and kit for autologous transplantation |
US5989269A (en) | 1996-08-30 | 1999-11-23 | Vts Holdings L.L.C. | Method, instruments and kit for autologous transplantation |
US8858981B2 (en) | 1997-10-10 | 2014-10-14 | Ed. Geistlich Soehne Fuer Chemistrie Industrie | Bone healing material comprising matrix carrying bone-forming cells |
US20050186283A1 (en) * | 1997-10-10 | 2005-08-25 | Ed. Geistlich Soehne Ag Fuer Chemistrie Industrie | Collagen carrier of therapeutic genetic material, and method |
US9034315B2 (en) | 1997-10-10 | 2015-05-19 | Ed. Geistlich Soehne Ag Fuer Chemische Industrie | Cell-charged multi-layer collagen membrane |
US20030180263A1 (en) * | 2002-02-21 | 2003-09-25 | Peter Geistlich | Resorbable extracellular matrix for reconstruction of bone |
EP1104313A2 (en) | 1998-08-14 | 2001-06-06 | Verigen Transplantation Service International (VTSI) AG | Methods, instruments and materials for chondrocyte cell transplantation |
FR2801313A1 (en) | 1999-05-19 | 2001-05-25 | Coletica | COLLAGENIC PRODUCT CONTAINING COLLAGEN OF MARINE ORIGIN WITH LOW ODOR AND PREFERREDLY WITH IMPROVED MECHANICAL PROPERTIES, AS WELL AS ITS USE IN THE FORM OF COMPOSITIONS OR COSMETIC OR PHARMACEUTICAL PRODUCTS |
EP1206225B1 (en) * | 1999-07-28 | 2005-03-09 | Interface Biotech A/S | In vitro repair of bone and/or cartilage defects |
DE19940977A1 (en) * | 1999-08-28 | 2001-03-01 | Lutz Claes | Film of resorbable polymer material and process for producing such a film |
US6221109B1 (en) * | 1999-09-15 | 2001-04-24 | Ed. Geistlich Söhne AG fur Chemische Industrie | Method of protecting spinal area |
DE19957388A1 (en) | 1999-11-24 | 2001-06-13 | Michael Sittinger | Chondroinductive and implantable substrates for cartilage healing and protection |
EP1233714B1 (en) * | 1999-11-30 | 2012-02-01 | Linvatec Biomaterials Ltd. | Bioabsorbable, osteopromoting fixation plate |
US6623963B1 (en) | 1999-12-20 | 2003-09-23 | Verigen Ag | Cellular matrix |
ES2238992T3 (en) * | 2000-03-09 | 2005-09-16 | Syntacoll Ag | COLLAR MATRIX OF MULTIPLE LAYERS FOR THE RECONSTRUCTION OF FABRIC. |
US6974679B2 (en) | 2000-05-26 | 2005-12-13 | Coletica | Support with collagen base for tissue engineering and manufacture of biomaterials |
FR2809313B1 (en) * | 2000-05-26 | 2005-11-18 | Coletica | PROCESSES FOR THE PREPARATION OF NEW COLLAGEN-BASED MEDIA FOR TISSUE ENGINEERING AND BIOMATERIALS OBTAINED |
US6790454B1 (en) | 2000-05-26 | 2004-09-14 | Coletica | Processes for the preparation of novel collagen-based supports for tissue engineering, and biomaterials obtained |
FR2809412A1 (en) | 2000-05-26 | 2001-11-30 | Coletica | Use of aquatic collagen for making supports for tissue engineering, particularly skin or tissue equivalents for surgical repair, studying aging processes and screening |
JP3865635B2 (en) * | 2000-05-26 | 2007-01-10 | エンゲルハード・リヨン | Collagen-based supports for tissue engineering and biomaterial manufacturing |
WO2001091821A1 (en) * | 2000-05-26 | 2001-12-06 | Coletica | Collagen-based supports for tissue engineering and preparation of biomaterials |
DK177997B1 (en) | 2000-07-19 | 2015-02-23 | Ed Geistlich Söhne Ag Für Chemische Ind | Bone material and collagen combination for healing of damaged joints |
US6773723B1 (en) * | 2000-08-30 | 2004-08-10 | Depuy Acromed, Inc. | Collagen/polysaccharide bilayer matrix |
US6692498B1 (en) | 2000-11-27 | 2004-02-17 | Linvatec Corporation | Bioabsorbable, osteopromoting fixation plate |
AU784394B2 (en) | 2001-04-27 | 2006-03-23 | Geistlich Pharma Ag | Method and membrane for mucosa regeneration |
AU2002354915B8 (en) * | 2001-07-16 | 2008-04-17 | Depuy Products, Inc. | Porous extracellular matrix scaffold and method |
JP4197159B2 (en) * | 2001-07-16 | 2008-12-17 | デピュイ・プロダクツ・インコーポレイテッド | Hybrid biosynthetic bioabsorbable scaffold material |
EP1416874A4 (en) * | 2001-07-16 | 2007-04-18 | Depuy Products Inc | Hybrid biologic/synthetic porous extracellular matrix scaffolds |
AU2002316696B2 (en) * | 2001-07-16 | 2007-08-30 | Depuy Products, Inc. | Cartilage repair and regeneration scaffold and method |
EP1416876B1 (en) * | 2001-07-16 | 2011-03-23 | DePuy Products, Inc. | Porous delivery scaffold and method |
JP4197158B2 (en) * | 2001-07-16 | 2008-12-17 | デピュイ・プロダクツ・インコーポレイテッド | Devices with naturally occurring biologically derived materials |
JP2003160506A (en) * | 2001-08-10 | 2003-06-03 | Ed Geistlich Soehne Ag Fuer Chemische Industrie | Collagen carrier of therapeutic genetic material and method |
US7465321B2 (en) | 2001-08-31 | 2008-12-16 | Keratec Limited | Production of biopolymer film, fibre, foam and adhesive materials from soluble S-sulfonated keratin derivatives |
CA2412012C (en) | 2001-11-20 | 2011-08-02 | Ed. Geistlich Soehne Ag Fuer Chemische Industrie | Resorbable extracellular matrix containing collagen i and collagen ii for reconstruction of cartilage |
WO2003061653A1 (en) * | 2002-01-22 | 2003-07-31 | Pfizer Limited | 3-(imidazolyl)-2-aminopropanoic acids for use as tafi-a inhibitors for the treatment of thrombotic diseases |
WO2003092542A2 (en) * | 2002-05-01 | 2003-11-13 | Verigen Ag | Injectable chondrocyte implant |
AU2002309229A1 (en) * | 2002-06-03 | 2003-12-19 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | A multi-layer collagenic article useful for wounds healing |
AU2003238745B2 (en) * | 2002-06-10 | 2008-12-11 | Keratec Limited | Orthopaedic materials derived from keratin |
US7166133B2 (en) | 2002-06-13 | 2007-01-23 | Kensey Nash Corporation | Devices and methods for treating defects in the tissue of a living being |
US20040034418A1 (en) * | 2002-07-23 | 2004-02-19 | Shu-Tung Li | Membrane-reinforced implants |
US20040136968A1 (en) * | 2002-09-27 | 2004-07-15 | Verigen Ag | Autologous cells on a support matrix for tissue repair |
JP4646487B2 (en) * | 2002-12-19 | 2011-03-09 | グンゼ株式会社 | Cartilage culture substrate and production method thereof |
US8173162B2 (en) | 2003-02-26 | 2012-05-08 | Zimmer Orthobiologics, Inc. | Preparation for repairing cartilage tissue, especially articular cartilage defects |
US20060083767A1 (en) * | 2003-02-27 | 2006-04-20 | Kai Deusch | Surgical prosthesis having biodegradable and nonbiodegradable regions |
JP5484648B2 (en) * | 2003-03-05 | 2014-05-07 | 株式会社高研 | Bone mineralization promoting factor |
US7572298B2 (en) * | 2003-03-28 | 2009-08-11 | Ethicon, Inc. | Implantable medical devices and methods for making same |
US7067123B2 (en) | 2003-04-29 | 2006-06-27 | Musculoskeletal Transplant Foundation | Glue for cartilage repair |
US7901457B2 (en) | 2003-05-16 | 2011-03-08 | Musculoskeletal Transplant Foundation | Cartilage allograft plug |
US7217294B2 (en) * | 2003-08-20 | 2007-05-15 | Histogenics Corp. | Acellular matrix implants for treatment of articular cartilage, bone or osteochondral defects and injuries and method for use thereof |
WO2005028560A1 (en) | 2003-09-19 | 2005-03-31 | Keratec Limited | Composite materials containing keratin |
DE10349722A1 (en) * | 2003-10-23 | 2005-06-16 | Beschorner, Katharina, Dr. | Composition for arthritis / arthritis treatment, in particular of joints |
JP2007528237A (en) | 2003-11-28 | 2007-10-11 | クック・インコーポレーテッド | Vessel occlusion method, system and apparatus |
EP1694370B1 (en) | 2003-12-19 | 2012-08-22 | Keratec Limited | Wound care products containing keratin |
AU2005229075A1 (en) | 2004-03-29 | 2005-10-13 | Cook Biotech Incorporated | Medical graft products with differing regions and methods and systems for producing the same |
CA2570623C (en) * | 2004-04-30 | 2013-06-18 | Sunstar Suisse Sa | Biocompatible membrane formed by a lamination-forming process or a powder electrostatic coating process |
US8697139B2 (en) | 2004-09-21 | 2014-04-15 | Frank M. Phillips | Method of intervertebral disc treatment using articular chondrocyte cells |
US7837740B2 (en) | 2007-01-24 | 2010-11-23 | Musculoskeletal Transplant Foundation | Two piece cancellous construct for cartilage repair |
US7579317B2 (en) | 2005-03-11 | 2009-08-25 | Keratec, Ltd. | Nutraceutical composition comprising soluble keratin or derivative thereof |
US7815926B2 (en) | 2005-07-11 | 2010-10-19 | Musculoskeletal Transplant Foundation | Implant for articular cartilage repair |
WO2007035778A2 (en) | 2005-09-19 | 2007-03-29 | Histogenics Corporation | Cell-support matrix and a method for preparation thereof |
US9005646B2 (en) | 2005-10-12 | 2015-04-14 | Lifenet Health | Compositions for repair of defects in tissues, and methods of making the same |
US9132208B2 (en) | 2008-08-07 | 2015-09-15 | Lifenet Health | Composition for a tissue repair implant and methods of making the same |
US20090246259A1 (en) | 2005-12-02 | 2009-10-01 | Kazuyoshi Kita | Biocompatible material having biocompatible non-woven nano- or micro-fiber fabric produced by electrospinning method, and method for production of the material |
ES2308709T3 (en) * | 2006-04-05 | 2008-12-01 | Opocrin S.P.A. | MULTIMICROLAMINARY COLLAGEN MEMBRANES. |
US20080026032A1 (en) * | 2006-07-27 | 2008-01-31 | Zubery Yuval | Composite implants for promoting bone regeneration and augmentation and methods for their preparation and use |
US9066994B2 (en) * | 2006-08-31 | 2015-06-30 | Warsaw Orthopedic, Inc. | Demineralized cancellous strip DBM graft |
DE102006042631A1 (en) * | 2006-09-05 | 2008-03-20 | Jotec Gmbh | Implant and method for its production |
CA2661389C (en) * | 2006-09-07 | 2016-04-12 | Ed. Geistlich Soehne Ag Fuer Chemische Industrie | Method of treating bone cancer |
US20080125863A1 (en) * | 2006-11-28 | 2008-05-29 | Mckay William F | Implant designs and methods of improving cartilage repair |
DK2099400T3 (en) | 2006-12-06 | 2014-10-20 | Weber Jeffrey A | BONE SPACES AND METHOD OF PRODUCING THEREOF |
US7871440B2 (en) | 2006-12-11 | 2011-01-18 | Depuy Products, Inc. | Unitary surgical device and method |
WO2008073376A2 (en) | 2006-12-11 | 2008-06-19 | Keratec, Ltd. | Porous keratin construct and method of making the same |
US20080147197A1 (en) * | 2006-12-14 | 2008-06-19 | Mckay William F | Biodegradable osteogenic porous biomedical implant with impermeable membrane |
US9592125B2 (en) | 2006-12-22 | 2017-03-14 | Laboratoire Medidom S.A. | In situ system for intra-articular chondral and osseous tissue repair |
US20080260794A1 (en) * | 2007-02-12 | 2008-10-23 | Lauritzen Nels J | Collagen products and methods for producing collagen products |
US9056151B2 (en) * | 2007-02-12 | 2015-06-16 | Warsaw Orthopedic, Inc. | Methods for collagen processing and products using processed collagen |
US8435551B2 (en) | 2007-03-06 | 2013-05-07 | Musculoskeletal Transplant Foundation | Cancellous construct with support ring for repair of osteochondral defects |
US20080255049A1 (en) * | 2007-04-10 | 2008-10-16 | Rush University Medical Center | Combined use of ultrasound and growth factors to stimulate bone formation |
CZ2007424A3 (en) * | 2007-06-21 | 2008-12-29 | Hypro Otrokovice, S. R. O. | Process for producing structured multilayer membrane, structured multilayer membrane per se and use thereof |
DE102007037051A1 (en) * | 2007-07-24 | 2009-01-29 | Aesculap Ag | Flat implant |
JP5179124B2 (en) * | 2007-09-06 | 2013-04-10 | 矢橋工業株式会社 | Bone regeneration inducing membrane and method for producing the same |
CA2717725A1 (en) | 2008-03-05 | 2009-09-11 | Musculoskeletal Transplant Foundation | Cancellous constructs, cartilage particles and combinations of cancellous constructs and cartilage particles |
US9616153B2 (en) * | 2008-04-17 | 2017-04-11 | Warsaw Orthopedic, Inc. | Rigid bone graft substitute |
US20100082113A1 (en) | 2008-04-29 | 2010-04-01 | Peter Gingras | Tissue repair implant |
DE102008022319A1 (en) * | 2008-04-30 | 2009-11-05 | Aesculap Ag | Implant, in particular for restoring and / or regenerating human and / or animal tissue |
US9242026B2 (en) * | 2008-06-27 | 2016-01-26 | Sofradim Production | Biosynthetic implant for soft tissue repair |
KR100947765B1 (en) * | 2008-08-18 | 2010-03-18 | (주)다림티센 | The matrix on base of collagen as restorative materal and the method of preparing it |
JP5698680B2 (en) * | 2009-01-16 | 2015-04-08 | ガイストリヒ・ファーマ・アクチェンゲゼルシャフトGeistlich Pharma Ag | Method and membrane for skin regeneration |
US8613943B2 (en) | 2009-01-23 | 2013-12-24 | Royal College Of Surgeons In Ireland | Process for producing a multi-layered scaffold suitable for osteochondral repair |
WO2010117766A1 (en) * | 2009-03-30 | 2010-10-14 | Osseous Technologies Of America | Collagen biomaterial wedge |
DE102009018640A1 (en) * | 2009-04-17 | 2010-10-21 | Tetec Tissue Engineering Technologies Ag | Implant and therapeutic composition for the treatment of damage and / or diseases in the field of the human and / or animal musculoskeletal system |
JP2011015865A (en) * | 2009-07-10 | 2011-01-27 | Nagoya Institute Of Technology | Material for filling bone defect and production method thereof |
US8853298B2 (en) | 2009-07-10 | 2014-10-07 | Nagoya Institute Of Technology | Fiber wadding for filling bone defects |
US8298586B2 (en) | 2009-07-22 | 2012-10-30 | Acell Inc | Variable density tissue graft composition |
JP5594815B2 (en) * | 2009-09-10 | 2014-09-24 | 国立大学法人 名古屋工業大学 | Bone regeneration inducing membrane and method for producing the same |
CN102573860A (en) | 2009-10-02 | 2012-07-11 | 巴克斯特国际公司 | Hematopoietic stem cells for use in the treatment of a kidney injury |
FR2955333B1 (en) * | 2010-01-15 | 2014-03-21 | Laboratoires Genevrier | USE OF A POROUS RETICULATED COLLAGEN II MATRIX AS A SUPPORT FOR CELL CULTURE AND REGENERATION OF CARTILAGINOUS TISSUE; |
US8790699B2 (en) | 2010-04-23 | 2014-07-29 | Warsaw Orthpedic, Inc. | Foam-formed collagen strand |
US8460691B2 (en) | 2010-04-23 | 2013-06-11 | Warsaw Orthopedic, Inc. | Fenestrated wound repair scaffold |
US8551525B2 (en) | 2010-12-23 | 2013-10-08 | Biostructures, Llc | Bone graft materials and methods |
DE102011002530A1 (en) * | 2011-01-11 | 2012-07-12 | Aesculap Ag | Medical product and process for its preparation, in particular for the regenerative treatment of cartilage damage |
FR2972626B1 (en) | 2011-03-16 | 2014-04-11 | Sofradim Production | PROSTHETIC COMPRISING A THREE-DIMENSIONAL KNIT AND ADJUSTED |
CN102716517B (en) * | 2011-03-30 | 2015-01-14 | 深圳兰度生物材料有限公司 | Guided tissue regeneration membrane and its preparation method |
FR2977790B1 (en) | 2011-07-13 | 2013-07-19 | Sofradim Production | PROSTHETIC FOR UMBILIC HERNIA |
FR2977789B1 (en) | 2011-07-13 | 2013-07-19 | Sofradim Production | PROSTHETIC FOR UMBILIC HERNIA |
FR2985170B1 (en) | 2011-12-29 | 2014-01-24 | Sofradim Production | PROSTHESIS FOR INGUINAL HERNIA |
JP2015508101A (en) | 2012-02-21 | 2015-03-16 | バクスター・インターナショナル・インコーポレイテッドBaxter International Incorp0Rated | Pharmaceutical composition comprising CD34 + cells |
US10071184B2 (en) * | 2012-02-29 | 2018-09-11 | Collagen Matrix, Inc. | Collagen-coated tissue-based membranes |
KR20150023294A (en) | 2012-05-30 | 2015-03-05 | 클록스 테크놀로지스 인크. | Compositions and Methods for Biophotonic Bone Reconstruction |
RU2505602C1 (en) * | 2012-06-04 | 2014-01-27 | Федеральное государственное бюджетное учреждение "Российский кардиологический научно-производственный комплекс" Министерства здравоохранения и социального развития РФ (ФГБУ "РКНПК" Минздравсоцразвития России) | Method for obtaining resident stem cells of mammal heart from myocard sample |
BR112015000670A2 (en) | 2012-07-11 | 2017-06-27 | Osiris Therapeutics Inc | cartilage product manufacturing methods |
FR2994185B1 (en) | 2012-08-02 | 2015-07-31 | Sofradim Production | PROCESS FOR THE PREPARATION OF A POROUS CHITOSAN LAYER |
WO2014041516A1 (en) | 2012-09-14 | 2014-03-20 | Ecole Polytechnique Federale De Lausanne (Epfl) | Biocompatible multi-layered structure comprising foam layers and a functional interface |
FR2995788B1 (en) | 2012-09-25 | 2014-09-26 | Sofradim Production | HEMOSTATIC PATCH AND PREPARATION METHOD |
FR2995779B1 (en) | 2012-09-25 | 2015-09-25 | Sofradim Production | PROSTHETIC COMPRISING A TREILLIS AND A MEANS OF CONSOLIDATION |
KR101434041B1 (en) | 2012-11-08 | 2014-08-29 | 주식회사 제네웰 | and method of preparing membrane for leading regeneration produced from material derived from biological tissue |
TWI487542B (en) | 2012-12-06 | 2015-06-11 | Ind Tech Res Inst | Bioresorbable porous film |
CN103897211A (en) * | 2012-12-26 | 2014-07-02 | 天津市赛宁生物工程技术有限公司 | Elastic cerebral dura mater |
EP2943205B1 (en) * | 2013-01-14 | 2018-08-22 | Scripps Health | Tissue array printing |
US9446077B2 (en) | 2013-03-13 | 2016-09-20 | Allosource | Fascia fibrous compositions and methods for their use and manufacture |
US9452240B2 (en) | 2013-03-15 | 2016-09-27 | Orthovita, Inc. | Pepsinized collagen implants and biomedical uses thereof |
CN103341211B (en) * | 2013-06-14 | 2014-10-29 | 张仲文 | Preparation method for I/II collagen double-layer composite collagen membrane |
CN103394126B (en) * | 2013-07-11 | 2014-12-31 | 陕西佰傲再生医学有限公司 | Cartilage repair material and preparation method thereof |
CN103394131B (en) * | 2013-07-26 | 2014-07-16 | 宁夏医科大学 | Novel double-layered composite transmitting tissue regeneration membrane and preparation method thereof |
RU2563621C2 (en) * | 2013-09-16 | 2015-09-20 | Федеральное государственное бюджетное учреждение науки Институт физики полупроводников им. А.В. Ржанова Сибирского отделения Российской академии наук (ИФП СО РАН) | Bioresorbable polymer cell matrix |
EP3116557B1 (en) | 2014-03-14 | 2020-03-11 | Scripps Health | Electrospinning of cartilage and meniscus matrix polymers |
CN105327392B (en) * | 2014-08-08 | 2018-07-27 | 北京中科再康生物技术有限公司 | A kind of orderly collagen-based materials and the preparation method and application thereof |
US10077420B2 (en) | 2014-12-02 | 2018-09-18 | Histogenics Corporation | Cell and tissue culture container |
WO2016126789A1 (en) * | 2015-02-03 | 2016-08-11 | University Of Maine System Board Of Trustees | Soft tissue in-growth of porous, three-dimensionally printed, transcutaneous implants of varying material and pore geometry |
EP3059255B1 (en) | 2015-02-17 | 2020-05-13 | Sofradim Production | Method for preparing a chitosan-based matrix comprising a fiber reinforcement member |
EP3085337B1 (en) | 2015-04-24 | 2022-09-14 | Sofradim Production | Prosthesis for supporting a breast structure |
ES2676072T3 (en) | 2015-06-19 | 2018-07-16 | Sofradim Production | Synthetic prosthesis comprising a knitted fabric and a non-porous film and method of forming it |
CN104958791B (en) * | 2015-07-29 | 2017-12-08 | 东莞博与再生医学有限公司 | A kind of glaucoma surgery compound bio matrix and preparation method thereof |
EP3195830B1 (en) | 2016-01-25 | 2020-11-18 | Sofradim Production | Prosthesis for hernia repair |
EP3463169B1 (en) | 2016-05-26 | 2023-07-19 | Scripps Health | Systems to repair tissue defects |
CN107913435B (en) * | 2016-10-10 | 2022-09-09 | 北京邦塞科技有限公司 | Composite type dura mater (spinal) membrane implant, preparation method and use thereof |
EP3312325B1 (en) | 2016-10-21 | 2021-09-22 | Sofradim Production | Method for forming a mesh having a barbed suture attached thereto and the mesh thus obtained |
US10772986B2 (en) | 2017-01-26 | 2020-09-15 | Allosource | Fascia fibrous compositions and methods for their use and manufacture |
EP3398554A1 (en) | 2017-05-02 | 2018-11-07 | Sofradim Production | Prosthesis for inguinal hernia repair |
KR102183048B1 (en) * | 2017-06-19 | 2020-11-25 | 주식회사 나이벡 | An assembled biomaterial for bone tissue regeneration and method for preparing the same |
CN109395095B (en) * | 2017-09-18 | 2021-09-24 | 武汉原生原代生物医药科技有限公司 | In vivo biological membrane and preparation method and application thereof |
CN110559486A (en) * | 2018-06-06 | 2019-12-13 | 常州药物研究所有限公司 | Composite collagen membrane for grafting bone in alveolar bone defect area and preparation method thereof |
CN108904885B (en) * | 2018-09-25 | 2021-02-09 | 清华大学深圳研究生院 | Controllable degradable biological water condensation film and manufacturing method and application thereof |
DE112020002263T5 (en) * | 2019-05-07 | 2022-01-20 | Preco, Inc. | Containment closure method for enclosing slack material and enclosing slack material |
CN110420359B (en) * | 2019-08-07 | 2021-11-19 | 北京奥精医疗器械有限责任公司 | Guided tissue regeneration membrane and preparation method thereof |
RU2713657C1 (en) * | 2019-08-15 | 2020-02-06 | Общество с ограниченной ответственностью «ОстеоНова» | Bioresorbable barrier membrane based on polysaccharide for directed regeneration of bone tissue |
CN110559479B (en) * | 2019-09-12 | 2021-12-07 | 苏州高哲斯环境新材料有限公司 | Preparation method of tissue regeneration guiding membrane for tooth restoration |
CN113398338B (en) * | 2021-06-30 | 2022-08-09 | 华东理工大学 | Double-layer repairing film for guiding tissue regeneration and preparation method thereof |
CN114259324B (en) * | 2021-12-24 | 2022-09-30 | 天新福(北京)医疗器材股份有限公司 | Preparation method of multilayer artificial dura mater |
CN114618026B (en) * | 2022-03-17 | 2023-09-12 | 西岭(镇江)医疗科技有限公司 | Barrier membrane capable of promoting bone regeneration and preparation method thereof |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4488911A (en) * | 1975-10-22 | 1984-12-18 | Luck Edward E | Non-antigenic collagen and articles of manufacture |
US5413597A (en) * | 1990-12-29 | 1995-05-09 | Krajicek; Milan | Three-layer vascular prostheses |
US5567806A (en) * | 1991-08-02 | 1996-10-22 | Abdul-Malak; Nabil | Collagen crosslinked with a crosslinking agent for the manufacture of a suturable, biocompatible slowresorbing membrane, and such a membrane |
US5763416A (en) * | 1994-02-18 | 1998-06-09 | The Regent Of The University Of Michigan | Gene transfer into bone cells and tissues |
US5891558A (en) * | 1994-11-22 | 1999-04-06 | Tissue Engineering, Inc. | Biopolymer foams for use in tissue repair and reconstruction |
US5942496A (en) * | 1994-02-18 | 1999-08-24 | The Regent Of The University Of Michigan | Methods and compositions for multiple gene transfer into bone cells |
US5965125A (en) * | 1995-10-25 | 1999-10-12 | Transkaryotic Therapies, Inc. | Hybrid matrix implants and explants |
US6221109B1 (en) * | 1999-09-15 | 2001-04-24 | Ed. Geistlich Söhne AG fur Chemische Industrie | Method of protecting spinal area |
US6752834B2 (en) * | 1997-10-10 | 2004-06-22 | Ed Geistlich Soehne Ag Fuer Chemische Industrie | Membrane for in guided tissue regeneration |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1990013302A1 (en) * | 1989-04-28 | 1990-11-15 | Brigham And Women's Hospital | Novel materials and methods for guided tissue regeneration |
JPH06292716A (en) * | 1993-04-09 | 1994-10-21 | Shimizu Yoshihiko | Medical material |
GB9400163D0 (en) * | 1994-01-06 | 1994-03-02 | Geistlich Soehne Ag | Membrane |
JPH083199A (en) * | 1994-06-15 | 1996-01-09 | Kaken Pharmaceut Co Ltd | Collagen-cartilage cell composite material |
US6080194A (en) * | 1995-02-10 | 2000-06-27 | The Hospital For Joint Disease Orthopaedic Institute | Multi-stage collagen-based template or implant for use in the repair of cartilage lesions |
GB9503492D0 (en) * | 1995-02-22 | 1995-04-12 | Ed Geistlich S Hne A G F R Che | Chemical product |
DE19654884C2 (en) | 1996-03-04 | 1999-07-29 | Kirsch Axel | Molded body |
-
1997
- 1997-10-10 GB GBGB9721585.9A patent/GB9721585D0/en not_active Ceased
-
1998
- 1998-10-05 DK DK98945439T patent/DK1023091T3/en active
- 1998-10-05 PL PL339835A patent/PL191497B1/en unknown
- 1998-10-05 CZ CZ20001295A patent/CZ297205B6/en not_active IP Right Cessation
- 1998-10-05 EP EP98945439A patent/EP1023091B1/en not_active Expired - Lifetime
- 1998-10-05 CN CNB988117347A patent/CN1181893C/en not_active Expired - Fee Related
- 1998-10-05 CA CA002305740A patent/CA2305740C/en not_active Expired - Fee Related
- 1998-10-05 AT AT98945439T patent/ATE286409T1/en active
- 1998-10-05 DE DE69828519T patent/DE69828519T2/en not_active Expired - Lifetime
- 1998-10-05 RU RU2000109319/14A patent/RU2217171C2/en not_active IP Right Cessation
- 1998-10-05 ES ES98945439T patent/ES2236936T3/en not_active Expired - Lifetime
- 1998-10-05 WO PCT/GB1998/002976 patent/WO1999019005A1/en active IP Right Grant
- 1998-10-05 JP JP2000515635A patent/JP4819995B2/en not_active Expired - Fee Related
-
2000
- 2000-04-07 US US09/545,465 patent/US6752834B2/en not_active Expired - Fee Related
-
2004
- 2004-06-18 US US10/869,909 patent/US20040234577A1/en not_active Abandoned
Patent Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4488911A (en) * | 1975-10-22 | 1984-12-18 | Luck Edward E | Non-antigenic collagen and articles of manufacture |
US5413597A (en) * | 1990-12-29 | 1995-05-09 | Krajicek; Milan | Three-layer vascular prostheses |
US5567806A (en) * | 1991-08-02 | 1996-10-22 | Abdul-Malak; Nabil | Collagen crosslinked with a crosslinking agent for the manufacture of a suturable, biocompatible slowresorbing membrane, and such a membrane |
US5763416A (en) * | 1994-02-18 | 1998-06-09 | The Regent Of The University Of Michigan | Gene transfer into bone cells and tissues |
US5942496A (en) * | 1994-02-18 | 1999-08-24 | The Regent Of The University Of Michigan | Methods and compositions for multiple gene transfer into bone cells |
US5891558A (en) * | 1994-11-22 | 1999-04-06 | Tissue Engineering, Inc. | Biopolymer foams for use in tissue repair and reconstruction |
US6153292A (en) * | 1994-11-22 | 2000-11-28 | Tissue Engineering, Inc. | Biopolymer foams for use in tissue repair and reconstruction |
US5965125A (en) * | 1995-10-25 | 1999-10-12 | Transkaryotic Therapies, Inc. | Hybrid matrix implants and explants |
US6752834B2 (en) * | 1997-10-10 | 2004-06-22 | Ed Geistlich Soehne Ag Fuer Chemische Industrie | Membrane for in guided tissue regeneration |
US6221109B1 (en) * | 1999-09-15 | 2001-04-24 | Ed. Geistlich Söhne AG fur Chemische Industrie | Method of protecting spinal area |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20080260801A1 (en) * | 2005-11-17 | 2008-10-23 | Gelita Ag | Composite material, especially for medical use, and method for producing the material |
WO2011091796A1 (en) * | 2010-01-27 | 2011-08-04 | UroTec GmbH | Tissue graft structure that can be sutured for reconstructing a human or animal organ |
WO2014010859A1 (en) * | 2012-07-09 | 2014-01-16 | 주식회사 오스코텍 | Production method for absorbent barrier membrane for inducing tissue regeneration |
KR101455837B1 (en) * | 2012-07-09 | 2014-11-03 | 주식회사 오스코텍 | Process for preparing resorbable barrier membrane for guided tissue regeneration |
CN107405422A (en) * | 2015-03-18 | 2017-11-28 | 富士胶片株式会社 | Regenerating bone or cartilage material and its manufacture method |
EP3260142A4 (en) * | 2015-03-18 | 2018-03-21 | FUJI-FILM Corporation | Cartilage regeneration material and method for producing same |
US11160902B2 (en) | 2015-03-18 | 2021-11-02 | Fujifilm Corporation | Cartilage regenerative material and method for producing same |
US11241518B2 (en) | 2015-03-18 | 2022-02-08 | Fujifilm Corporation | Cartilage regenerative material |
Also Published As
Publication number | Publication date |
---|---|
CZ297205B6 (en) | 2006-10-11 |
DE69828519T2 (en) | 2005-12-29 |
CA2305740A1 (en) | 1999-04-22 |
EP1023091B1 (en) | 2005-01-05 |
PL191497B1 (en) | 2006-05-31 |
ATE286409T1 (en) | 2005-01-15 |
RU2217171C2 (en) | 2003-11-27 |
WO1999019005A1 (en) | 1999-04-22 |
PL339835A1 (en) | 2001-01-02 |
US6752834B2 (en) | 2004-06-22 |
EP1023091A1 (en) | 2000-08-02 |
ES2236936T3 (en) | 2005-07-16 |
DE69828519D1 (en) | 2005-02-10 |
GB9721585D0 (en) | 1997-12-10 |
CN1181893C (en) | 2004-12-29 |
JP2001519210A (en) | 2001-10-23 |
US20020177903A1 (en) | 2002-11-28 |
DK1023091T3 (en) | 2005-02-14 |
JP4819995B2 (en) | 2011-11-24 |
CN1280509A (en) | 2001-01-17 |
CZ20001295A3 (en) | 2000-10-11 |
CA2305740C (en) | 2009-07-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6752834B2 (en) | Membrane for in guided tissue regeneration | |
US7141072B2 (en) | Method for promoting regeneration of surface cartilage in a damaged joint using multi-layer covering | |
AU2002300450B2 (en) | Collagen Carrier of Therapeutic Genetic Material, and Method | |
US8911763B2 (en) | Collagen carrier of therapeutic genetic material and method | |
US20050186673A1 (en) | Collagen carrier of therapeutic genetic material, and method | |
US8354119B2 (en) | Resorbable extracellular matrix containing collagen I and collagen II for reconstruction of cartilage | |
US7208177B2 (en) | Resorbable extracellular matrix for reconstruction of cartilage | |
JP2010075718A (en) | Resorbable extracellular matrix for reconstruction of bone | |
JP2010075709A (en) | Collagen carrier of therapeutic genetic material, and method therefor | |
US8858981B2 (en) | Bone healing material comprising matrix carrying bone-forming cells | |
WO2011064724A1 (en) | Biomimetic composite materials, preparation process thereof and use thereof to produce mono-, bi- or multi -layer structures for the regeneration of bone, cartilaginous and osteocartilaginous tissue | |
AU2012200086A1 (en) | Resorbable Extracellular Matrix for Reconstruction of Bone | |
AU2007254593A1 (en) | Resorbable Extracellular Matrix for Reconstruction of Bone |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |