CA2264138C - Method, instruments and kit for autologous transplantation - Google Patents
Method, instruments and kit for autologous transplantation Download PDFInfo
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- CA2264138C CA2264138C CA002264138A CA2264138A CA2264138C CA 2264138 C CA2264138 C CA 2264138C CA 002264138 A CA002264138 A CA 002264138A CA 2264138 A CA2264138 A CA 2264138A CA 2264138 C CA2264138 C CA 2264138C
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- cartilage
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- 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
- A61F2/2846—Support means for bone substitute or for bone graft implants, e.g. membranes or plates for covering bone defects
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- 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
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- 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
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- 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
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- 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
- A61F2/38—Joints for elbows or knees
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- 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
- A61F2002/2835—Bone graft implants for filling a bony defect or an endoprosthesis cavity, e.g. by synthetic material or biological material
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- 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
- A61F2002/30004—Material related properties of the prosthesis or of a coating on the prosthesis the prosthesis being made from materials having different values of a given property at different locations within the same prosthesis
- A61F2002/30016—Material related properties of the prosthesis or of a coating on the prosthesis the prosthesis being made from materials having different values of a given property at different locations within the same prosthesis differing in hardness, e.g. Vickers, Shore, Brinell
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- 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
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- 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
- A61F2002/30316—The prosthesis having different structural features at different locations within the same prosthesis; Connections between prosthetic parts; Special structural features of bone or joint prostheses not otherwise provided for
- A61F2002/30535—Special structural features of bone or joint prostheses not otherwise provided for
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- 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
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- 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
- A61F2002/30762—Means for culturing cartilage
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2250/0014—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis
- A61F2250/0019—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis differing in hardness, e.g. Vickers, Shore, Brinell
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2250/0058—Additional features; Implant or prostheses properties not otherwise provided for
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- 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
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- 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
Abstract
Method for the effective transplantation of chondrocytes/cartilage to an articular joint surface defect is taught, as well as a description of certai n instruments and kit for practicing the invention.
Description
1015202530CA 02264138 1999-02-26wo 98/118469 PCTIUS97Il5258Method, Instruments and Kit for Autologous TransplantationField of the InventionThe instant invention concerns the ï¬eld of chondrocyte transplantation, bone andcartilage graï¬ing, healing, joint repair and the prevention of arthritic pathologies. Inparticular methods for the preparation of the graft site, instruments for such preparation andfor the autologous transplantation of cells to the prepared graft site.Background of the InventionMore than 500,000 arthroplastic procedures and total joint replacements areperformed each year in the United States. Approximately the same number of similarprocedures are performed in Europe. Included in these numbers are about 90,000 total-kneereplacements and around 50,000 procedures to repair defects in the knee per year in Europe.The number of procedures are essentially the same in the U. S. (In: Praemer A., Fumer S.,Rice, D.P., Musculoskeletal conditions in the United States, American Academy ofOrthopaedic Surgeons, Park Ridge, Ill., 1992, 125). A method for regeneration-treatment ofcartilage would be most useful, and could be performed at an earlier stage of joint damage,thus reducing the number of patients needing artificial joint replacement surgery. With suchpreventative methods of treatment, the number of patients developing osteoarthritis wouldalso decrease.Techniques used for resurfacing the cartilage structure in joints have mainlyattempted to induce the repair of cartilage using subchondral drilling, abrasion and othermethods whereby there is excision of diseased cartilage and subchondral bone, leavingvascularized cancellous bone exposed (Insall, J., Clin. Orthop. 1974,101,61; Ficat R.P. er al,Clin Orthop. 1979, 144, 74', Johnson L.L., ln: Qgerative Arthroscopy, McGinty J.B.. Ed.,Raven Press, New York, 1991, 341).Coon and Cahn (Science 1966, 153, 1116) described a technique for the cultivationof cartilage synthesizing cells from chick embryo somites. Later Cahn and Lasher (PNASUSA 1967, 58, 1131) used the system for analysis of the involvement of DNA synthesis asa prerequisite for cartilage differentiation. Chondrocytes respond to both EFG and FGF bygrowth (Gospodarowicz and Mescher, J. Cell Physiology 1977, 93, 117), but ultimatelyl10I5202530CA 02264138 1999-02-26WO 98108469 PCTIUS97I15258lose their differentiated function (Benya et al., Cell 1978, 15, 1313). Methods for growingchondrocytes were described and are principally being used with minor adjustments byBrittberg, M. et al. (New Engl. J. Med. 1994, 331, 889). Cells grown using these methodswere used as autologous transplants into knee joints of patients. Additionally, Kolettas et al.(J. Cell Science 1995, 108, 1991) examined the expression of cartilage-speciï¬c moleculessuch as collagens and proteoglycans under prolonged cell culturing. They found that despitemorphological changes during culturing in monolayer cultures (Aulthouse, A. et al., InVitro Cell Dev. Biol., l989,25,659; Archer, C. et al., J. Cell Sci. 1990,97,36l; Héinselmarm,H. et al., J. Cell Sci. 1994,lO7,l7; Bonaventure, J. et al., Exp. Cell Res. l994,2l2,97), whencompared to suspension cultures grown over agarose gels, alginate beads or as spinnercultures (retaining a round cell morphology) tested by various scientists did not change thechondrocyte - expressed markers such as types II and IX collagens and the largeaggregating proteoglycans, aggrecan, versican and link protein did not change (Kolettas, E.et al., J. Cell Science l99S,108,l99l).The articular chondrocytes are specialized mesenchymal derived cells foundexclusively in cartilage. Cartilage is an avascular tissue whose physical properties dependon the extracellular matrix produced by the chondrocytes. During endochondral ossiï¬cationchondrocytes undergo a maturation leading to cellular hypertrophy, characterized by theonset of expression of type X collagen (Upholt, W.B. and Olsen, R.R., In: CmjlggeMolecular Aspects (Hall, B & Newman, S, Eds.) CRC Boca Raton 1991, 43;Reichenberger, E. et al., Dev. Biol. 1991, 148, 562; Kirsch, T. et al., Differentiation, 1992,52, 89; Stephens, M. et al., J. Cell Sci. 1993, 103, 1111).Excessive degredation of type II collagen in the outer layers or articular surfaces ofjoints is also caused by osteoarthritis. The collagen network is accordingly weakened andsubsequently develops ï¬brillation whereby matrix substances such as proteoglycans are lostand eventually displaced entirely. Such ï¬brillation of weakened osteoarthritic cartilage canreach down to the calcified cartilage and into the subchondral bone (Kempson, G.E. et al.,Biochim. Biophys. Acta 1976, 428, 741; Roth, V. and Mow. V.C., J. Bone Joint Surgery,1980, 62A, 1102; Woo, S.L.-Y. et al., in Handbook of Bioengineering (R. Skalak and S.Chien eds.), McGraw-Hill, New York, 1987, pp. 4.1-4.44).Ix)I015202530CA 02264138 1999-02-26wo 93/03459 PCT/US97/15258Descriptions of the basic development, histological and microscopic anatomy ofbone, cartilage and other such connective tissues can be found for example in Wheater,Burkitt and Daniels, Functional Histology, 2"â Edition, (Churchill Livingstone, London,1987, Chp. 4). Descriptions of the basic histological anatomy of defects in bone, cartilageand other connective tissue can be found for example in Wheater, Burkitt, Stevens andLowe, Basic Histogathology, (Churchill Livingstone, London, 1985. Chp. 21).Despite the advances in cultivating chondrocytes, and manipulating bone andcartilage, there has not been great success with the attempts to transplant cartilage orchondrocytes for the repair of damaged articulating surfaces. The teachings of the instantinvention provide for effective and efficient means of promoting the transplantation ofcartilage and/or chondrocytes into a defect in an articulating joint or other cartilage coveredbone surface, whereby cartilage is regenerated to fix the defect. The instant invention alsoprovides for surgical instruments which are designed prepare the graft site so as to facilitatethe efï¬cient integration of grafted material to the graft site.Brief Summary of the InventionThe instant invention provides a method for the effective treatment of articulatingjoint surface cartilage by the transplantation of chondrocytes in a suitable matrix, to asurface to be treated, with a hemostatic barrier and a cellâfree covering-patch comprising;first placing a hemostatic barrier proximal to the surface to be treated, placing chondrocytesin a suitable matrix upon the surface to be treated distal to the hemostatic barrier, coveringthe surface to be treated with a cellâfree covering-patch. A hemostatic banier, as will befurther described below, is a barrier which inhibits or prevents the penetration ofvascularizing cells and tissue into the grafted material. In particular, the instant methodprovides for a hemostatic ba.rrier that is a resorbable, semi-perrneable material whichinhibits or prohibits vascular inï¬ltration through the barrier. In one embodiment thehemostatic barrier contains collagen. Cell-free, is used herein as in the art, and means amaterial that is substantially free from intact cells which are capable of further cell division.promulgation or biological activity. In a preferred embodiment, a cell-free material is freefrom all intact nucleated cells. In one embodiment, the instant method encompasses the useof a cellâfree covering patch which contains a semiâperrneab1e collagen matrix. In one202530CA 02264138 1999-02-26wo 93/03459 PCTIUS97ll5258preferred embodiment of the method, the porous surface of the cell-free coveringâpatch isdirected towards the implant material.The instant invention further provides for the autologous transplantation of collagenor chondrocytes to a graft site, wherein the graft site has first been prepared by surgicalmanipulation to better accept the grafted material. In one embodiment. the graft site issculpted such that the walls of the graft site are contoured in an undulating pattern such thatthe grafted material, when placed within the graft site and expanded to contact the graft sitewall, there will be resistance against removal or expulsion of the entire graft from the graftsite. The instant invention further provides for surgical instruments designed to sculpt thegraft site as taught by the method of the invention.The invention further provides for a kit for cartilage and/or chondrocytetransplantation onto the surface of an articular joint wherein said kit comprises a hemostaticbarrier, cellâfree semi-permeable covering-patch, and organic glue. In a furtherembodiment, the kit can optionally further provide one or more surgical instruments whichcan be used to sculpt the graft site in accordance with the methods of the instant invention.Brief Description of the DrawingsThe present invention will be better understood by examining the following figureswhich illustrate certain properties of the instant invention wherein:Figure 1A is a drawing showing a typical articulating end of a bone. Typically, thebone material is covered on the articulating surface with a cartilaginous.Figure 1B shows an example of where a defect or injury to the cartilaginous capoccurs (gap in cartilage), and such a defect can be treated directly, enlarged slightly, orsculpted to accept the grafted material by surgical procedures prior to treatment.Figure 1C shows how the hemostatic barrier (numbered 1) is placed within thedefect in the cartilage cap to inhibit or prevent vascularization into regenerating cartilage,from the underlying bone. The chondrocytes to be implanted into the defect cavity are thenlayered on top of the hemostatic barrier.Figure 2 is a drawing showing the treated defect (gap in cartilage) in thecartilaginous cap covered by a cellâfree semi-penneable material (numbered 2) which isused to form a cap/patch or bandage over the defect site. This cap is fixed in place, either10I5202530CA 02264138 2002-06-17sutured to the edge of the cavity into healthy cartilage, or otherwise attached. This cap iscovering the defective area of the joint into which the cultured chondrocytes/cartilagetransplant has been placed, or will be placed under the partially attached cap.Figure 3A is a diagram illustrating the differential response to compression andshearing forces by left side and right side cartilage with subsequent zone of demarcation.Figure 3B illustrates the graft site, after the defect has been sculpted to haveundulating walls.Figure 3C illustrates the sculpted graft site with the hemostatic barrier (1),transplanted material (3), and cell-free covering-patch (2) in place within the articularsurface cartilage (4).Figure 4A illustrates one embodiment of the surgical device of the instant inventionshowing cutting teeth (5) and protruding placement pin (6). The crossâsection illustrationsto the right show two possible configurations of the cutting blades.Figure 4B illustrates a second embodiment of the surgical device of the instantinvention.Figure 5 is a diagram illustrating the modiï¬ed differential response to compressionand shearing forces by harder cartilage and softer cartilage after sculpting the graft site.Figure 6A is an MRI image of a pig knee showing cartilage defect in left (medial)condyle.Figure 6B is an MRI image of the same pig knee three months after treatment.Detailed Description of the lnventionThis invention concerns the use of certain products that inhibit the formation ofvascular tissue, for instance such as capillary loops projecting into the cartilage beingestablished, during the process of autologous transplantation of chondrocytes into defects inthe cartilage. The formation of vascular tissue from the underlying home will tend to projectinto the new cartilage to be formed leading to appearance of cells other than themesenchymal specialized chondrocytes desired.The contaminating cells introduced by the vascularization may give rise toencroachment and over-growth into the cartilage to be formed by the implantedchondrocytes. One of the types of commercial products which can be used in -this inventionis Surgicalâ (Ethicon Ltd., UK) which is absorbable after a period of 7 â 14 days. The use ofthis material in the method of the instant invention is contrary to the normal use of a1015202530CA 02264138 1999-02-26WO 98108469 PCTIUS97/ 15258hemostatic device, such as Surgicel° as it is described in the package insert from EthiconLtd.Surprisingly, we have found that in a situation where you wish to inhibit re-vascularization into cartilage, a hemostatic material will act like a gelâlike artiï¬cialcoagulate. If red blood cells should be present within the full-thickness defect of articularcartilage that is capped by such a hemostatic barrier, these blood cells will be chemicallychanged to hematin, and thus rendered unable to induce vascular growth. Thus a hemostaticproduct used as a re-vascularization inhibitory barrier with or without fibrin adhesives, suchas for example the Surgicelâ, is effective for the envisioned method as taught by the instantinvention. Another part of this invention is the use of a cell-free component, that is used asa patch covering the defective area of the joint into which the culturedchondrocytes/cartilage are being transplanted, using autologous chondrocytes for thetransplantation. The method of the invention also contemplates the use of suitable allogenicchondrocytes or xenogenic chondrocytes for the repair of a cartilage defect.Thus the instant invention teaches methods for effective repair or treatment ofcartilage defects in articular joint bone surfaces which comprises administering an agent ordevice to block vascular invasion into the cartilage site to be repaired, and also providingfor a cell-free barrier which will isolate the repair site and keep transplanted cells in place.Thus the instant invention also provides for a kit comprising a hemostatic barriercomponent for insertion into the site to be repaired, such that there is effective inhibition ofvascularization into the site to be repaired; and once the chondrocytes to be transplanted areplaced into the site to be repaired, a cell-free semi-pemieable barrier is capped over therepair site such that the transplanted chondrocytes are held in place, but are still able to gainaccess to nutrients.Certain aspects of the invention have been exemplified using an in vitra system tostudy the behavior of the chondrocytes when in contact with a certain product or acombination of certain products that inhibit the formation of vascular tissue. This in vitrotesting predicts the ability of certain tested materials to inhibit vascularization, as will occurin viva where capillary loops project into the cartilage being established during the processof autologous transplantation of chondrocytes into defects in the cartilage.Suitable hemostatic products will be characterized by having the ability to inhibitthe growth, or invasion of vascular tissue, osteocytes, fibroblasts etc. into the developingcartilage. A suitable hemostatic material will achieve the goal of the method of the instantIOI5202530CA 02264138 1999-02-26wo 93/03459 PCT lUS97I15258invention in that vascular and cellular invasion into developing cartilage should beprevented in order to optimize the formation of cartilage and achieve repair of the full-thickness of any defects in the articular cartilage. Ideally, the hemostatic barrier will bestable for an extended period of time sufficient to allow for full cartilage repair, and then beable to be resorbed or otherwise broken down over time. One material identified as suitableis called Surgicelâ W1912 (an absorbable hemostat containing oxidized regenerated sterilecellulose; Lot GG3DH, Ethicon Ltd. UK ). Another example of a suitable material isBioGide® (a commercially available type I collagen matrix pad; Geistlich Sohne,Switzerland).Suitable organic glue material can be found commercially, such as for exampleTisseel"â or Tissucol° (ï¬brin based adhesive; Immuno AG. Austria), Adhesive Protein (Cat.#A-2707, Sigma Chemical, USA), and Dow Corning Medical Adhesive B (Cat. #895â3,Dow Corning, USA).The surgical instruments contemplated by the instant invention can be manufacturedfrom metal and/or plastic suitable for making single-use disposable, or multi-use reusablesurgical instruments. The cutting instrument may contain cutting teeth that are fully circularor ï¬at, or anything in between. As cartilage is a relatively soft material it may beadvantageous to manufacture hardened plastic cutting edges which will be able to sculptcartilage without being able to damage bone. Such cutting instruments can be manufacturedto incorporate openings for administration of ï¬uid, suction removal of cutting debris andï¬uid, and fiber optic threads for illumination and visualization of the defect site.Certain aspects of the instant invention may be better understood as illustrated bythe following examples, which are meant by way of illustration and not limitation.Example 1In order for the Surgicel °ââ to be used according to the invention for preventingdevelopment of blood vessels into autologous implanted cartilage or chondrocytes,Surgicelâ was first treated with a fixative, such as glutaric aldehyde. Brieï¬y, Surgicelâ wastreated with 0.6% glutaric aldehyde for 1 minute, followed by several washings to eliminateglutaric aldehyde residues that may otherwise be toxic to tissue. Alternatively, theSurgicelâ was treated with the ï¬brin adhesive called Tisseel® prior to treatment withglutaric aldehyde as described in Example 2. It was found that the Surgicelâ ï¬xated forinstance with a ï¬xative such as glutaric aldehyde, washed with sterile physiological saline71015202530CA 02264138 1999-02-26wo 93/03459 PCT/US97/ 15258(0.9%) and stored in refrigerator, does not dissolve for 1 to 2 months. Generally, Surgical isresorbed in a period between 7 and 14 days. This time would be too short, because a longertime is needed in preventing the development of blood vessels or vascularization as suchfrom the bone structure into the implanted cartilage before the implanted chondrocytes havegrown into a solid cartilage layer getting its nutrition requirements from the neighboringcartilage. In other words sufficient inhibition of the vascularization is needed for a longertime such as for instance one month. Therefore, the product should not be absorbedsigniï¬cantly prior to that time. On the other hand resorption is needed eventually. Hence,the organic material used as an inhibiting barrier shall have these capabilities, and it hasbeen found that the Surgicalâ treated in this manner provides that function.Example 2The Surgicelâ was also coated with an organic glue. in this example the glue usedwas Tisseelâ but others can also be used. This product, together with the Surgicelâ producesa useable barrier for the particular purpose of the invention. Any other hemostat or vascularinhibiting barrier could be used. The Tisseelââ was mixed as described below. The Surgicel°was then coated with Tisseel° by spraying the Surgicelâ° material on both sides until soaked.The Tisseel° (ï¬brin glue) was then allowed to solidify at room temperature. Immediatelyprior to completed solidiï¬cation, the coated Surgicelâ was then placed in 0.6% glutaricaldehyde for 1 minute and then washed with sterile physiological (0.9%) saline. The pHwas then adjusted by PBS and/or with NaOH until pH was stable at 7.2 to 7.4. Afterwardsthe thus treated Surgicelw was then washed in tissue culture medium such as minimumessential medium/F12 with 15 mM Hepes buffer.As mentioned in this example we have used Tisseel® as the ï¬brin adhesive to coatthe Surgicelâ. Furthermore the ï¬brin adhesive or glue may also be applied directly on thebottom of the lesion towards the bone, on which the Surgieel® is glued. The in vitro systemused, in lieu of in vivo testing, consisted of a NUNCLONTM Delta 6-well sterile disposableplate for cell research work (NUNC, lnterMed, Roskilde, Denmark). Each well measuresapproximately 4 cm in diameter.In the invention the ï¬brin adhesive can be any adhesive which together with theï¬brin component will produce a glue that can be tolerated in humans (Ihara, N, et al., BurnsIncl. Therm. Inj., 1984, 10, 396). The invention also anticipates any other glue componentthat can be used in lieu of the fibrin adhesive. In this invention we used Tisseelâ orl0l5202530CA 02264138 1999-02-26PCT/US97/15258WO 98/08469Tissucol® (Immuno AG, Vienna, Austria). The Tisseel® kit consists of the followingcomponents:Tisseelâ, a lyophilized, virus-inactivated Sealer, containing clottable protein,thereof: ï¬brinogen, Plasma frbronectin (CIG) and Factor XIII, and Plasminogen.Aprotinin Solution (bovine)Thrombin 4 (bovine)Thrombin 500 (bovine)Calcium Chloride solutionThe Tisseelâ kit contains a DUPLOJECTâ Application System. The ï¬brin adhesiveor the two-component sealant using Tisseelo Kit is combined in the following manneraccording to the Immuno AG product insert sheet:Example 3Chondrocytes were grown in minimal essential culture medium containing HAMF12 and 15 mM Hepes buffer and 5 to 7.5% autologous serum in a C02 incubator at 37°Cand handled in a Class 100 laboratory at Verigen Europe A/S, Symbion Science Park,Copenhagen, Denmark. Other compositions of culture medium may be used for culturingthe chondrocytes. The cells were trypsinized using trypsin EDTA for 5 to 10 minutes andcounted using Trypan Blue viability staining in a Btlrker-Tiirk chamber. The cell count wasadjusted to 7.5 x 105 cells per ml. One NUNCLONTM plate was uncovered in the Class 100laboratory.The Surgicelâ hemostatic barrier was cut to a suitable size ï¬tting into the bottom ofthe well in the NUNCLONW tissue culture tray. In this case a circle, of a size ofapproximately 4 cm (but could be of any possible size) and placed under aseptic conditionson the bottom in well in a NUNCLONTâ Delta 6-well sterile disposable plate for cellresearch work (NUNC, lnterMed, Roskilde, Denmark). The hemostatic barrier to be placedon the bottom of the well was preâtreated as described in Example 1. This treatment delaysthe absorption of the Surgicel significantly. This hemostatic banier was then washedseveral times in distilled water and subsequently several times until non-reactedglutaraldehyde was washed out. A small amount of the cell culture medium containingserum was applied to be absorbed into the hemostatic barrier and at the same time keepingthe hemostatic barrier wet at the bottom of the well.Approximately 10° cells in 1 ml culture medium were placed directly on top of the910202530CA 02264138 1999-02-26W0 98/084659 PCTIUS97I 15258hemostatic barrier, dispersed over the surface of the hemostatic banier pre-treated with0.4% glutaraldehyde as described above. The plate was then incubated in a CO, incubator at37°C for 60 minutes. An amount of 2 to 5 ml of tissue culture medium containing 5 to 7.5%serum was carefully added to the well containing the cells avoiding splashing the cells byholding the pipette tip tangential to the side of the well when expelling the medium. Itappeared that the pH of the medium was too low (pH -6.8). The pH was then adjusted to7.4 to 7.5. The next day some chondrocytes had started to grow on the hemostatic barrier,arranged in clusters. Some of the cells had died due to the low pH exposure prior to theadjustment of the pH. The plate was incubated for 3 to 7 days with medium change at day3.At the end of the incubation period the medium was decanted and cold refrigerated2.5% glutaraldehydc containing 0.1M sodium salt of dimethylarsinic acid, (also calledsodium cacodylate, pH is adjusted with HCl to 7.4), was added as ï¬xative for preparation ofthe cell and supporter (hemostatic barrier) for later preparation for electron microscopy.Example 4Chondrocytes were grown in minimal essential culture medium containing HAMF12 and 15 mM Hepes buffer and 5 to 7.5% autologous serum in a C03 incubator at 37°Cand handled in a Class 100 laboratory at Verigen Europe A/S, Symbion Science Park,Copenhagen, Denmark. Other compositions of culture medium may be used for culturingthe chondrocytes. The cells were trypsinized using trypsin EDTA for 5 to 10 minutes andcounted using Trypan Blue viability staining in a Bï¬rker-Turk chamber. The cell count wasadjusted to 7.5 x 105 cells per ml. One NUNCLONTâ plate was uncovered in the Class 100laboratory.The Surgicel" (for use as the hemostatic barrier) was treated with 0.6% glutaricaldehyde for one minute as described in Example 1, and washed with 0.9% sterile sodiumchloride solution or, preferably, with a buffer such as a PBS buffer or the culture mediumsuch as MEM/F12, because pH after the glutaric aldehyde treatment is 6.8 and shouldpreferably be 7.0 to 7.5. The Tisseel° was applied on both side of the Surgicel°° using theDUPLOJECTQ system, thus coating both sides of the Surgicel®, the patch intended to beused, with fibrin adhesive. The glue is left to dry under aseptic condition for at least 3 to 5minutes. The "coated" hemostatic ban'ier was placed on the bottom of the well in aNUNCLONTM Delta 6-well sterile disposable plate for cell research work. A small amount101015202530CA 02264138 1999-02-26wo 93/03459 PCTIUS97/15258of tissue culture medium containing serum was applied to be absorbed into the hemostaticbarrier. Approximately 10° cells in 1 ml tissue culture medium containing serum wasplaced directly on top of the Hemostat, dispersed over the surface of the hernostatic barrier.The plate was then incubated in a CO: incubator at 37°C for 60 minutes. An amount of 2 to5 ml of tissue culture medium containing 5 to 7.5 % serum was carefully added to the wellcontaining the cells avoiding splashing the cells by holding the pipette tip tangential to theside of the well when expelling the medium. After 3 to 6 days, microscopic examinationshowed that the cells were adhering to and growing into the Surgicel° in a satisfactory waysuggesting that Surgicelâ did not show toxicity to the chondrocytes and that thechondrocytes grew in a satisfactory manner into the Surgicel°.The plate was incubated for 3 to 7 days with medium change at day 3. At the end ofthe incubation period the medium was decanted and cold refrigerated 2.5% glutaraldehydecontaining O.lM sodium salt of dimethylarsinic acid, also called sodium cacodylate, pH isadjusted with HCl to 7.4, was added as fixative for preparation of the cell and supporter(hemostatic barrier) for later preparation for electron microscopy.Example 5Chondrocytes were grown in minimal essential culture medium containing HAMF12 and 15 mM Hepes buffer and 5 to 7.5% autologous serum in a CO, incubator at 37°Cand handled in a Class 100 laboratory at Verigcn Europe A/S, Syrnbion Science Park,Copenhagen, Denmark. The cells were trypsinized using trypsin EDTA for 5 to 10 minutesand counted using Trypan Blue viability staining in a Biirker-Turk chamber. The cell countwas adjusted to 7.5 x 105 to 2 x 10" cells per ml. One NUNCLONTâ plate was uncovered inthe Class 100 laboratory.It has been found that the Bio-Gideâ can be used as a resorbablc bilayer membranewhich will be used as the patch or bandage covering the defective area of the joint intowhich the cultured chondrocytes are being transplanted as well as the hemostatic barrier.The Bio-Gideâ is a pure collagen membrane obtained by standardized, controlledmanufacturing processes (by E.D. Geistlich Sohne AG, CH-6110 Wolhusen). The collagenis extracted from veterinary certiï¬ed pigs and is carefully puriï¬ed to avoid antigenicreactions, and sterilized in double blisters by 7-irradiation. The bilayer membrane has aporous surface and a dense surface. The membrane is made of collagen type I and type IIIwithout further cross-linking or chemical treatment. The collagen is resorbed within 24lll0l5202530CA 02264138 1999-02-26wo 98I08469 PCT/US97ll5258weeks. The membrane retains its structural integrity even when wet and it can be ï¬xed bysutures or nails. The membrane may also be "glued" using ï¬brin adhesive such as Tisseel®to the neighboring cartilage or tissue either instead of sutures or together with sutures.The Bio-Gideâ was un-covered in a class 100 laboratory and placed under asepticconditions on the bottom of the wells in a NUNCLONTâ Delta 6âwell sterile disposableplate for cell research work, - either with the porous surface of the bilayer membrane facingup or with the dense surface facing up. Approximately 10° cells in 1 ml tissue culturemedium containing serum was placed directly on top of the BioâGide°, dispersed eitherover the porous or the dense surface of the Bio-Gideâ. The plate was then incubated in aC02 incubator at 37°C for 60 minutes. An amount of 2 to 5 ml of tissue culture mediumcontaining 5 to 7.5 % serum was carefully added to the well containing the cells avoidingsplashing the cells by holding the pipette tip tangential to the side of the well whenexpelling the medium.On day 2 after the chondrocytes were placed in the well containing the BioâGide°the cells were examined in a Nikon Inverted microscope. It was noticed that somechondrocytes had adhered to the edge of the Bio-Gide. It was of course not possible to beable to look through the Bio-Gideâ itself using this microscope.The plate was incubated for 3 to 7 days with medium change at day 3. At the end ofthe incubation period the medium was decanted and cold refrigerated 2.5% glutaraldehydecontaining 0.1M sodium salt of dimethylarsinic acid, also called sodium cacodylate, pH isadjusted with HCl to 7.4, was added as ï¬xative for preparation of the cell and the Bio-Gide° supporter with the cells either cultured on the porous surface or the dense surface.The Bio-Gideâ patches were then sent for electron microscopy at Department of Pathology,Herlev Hospital, Denmark.The electron microscopy showed that the chondrocytes cultured on the densesurface of the Bio-Gideâ did not grow into the collagen structure of the Bio-Gideâ, whereasthe cells cultured on the porous surface did indeed grow into the collagen structure andfurthennore, showed presence of proteoglyeans and no signs of fibroblast structures. Thisresult shows that when the collagen patch, as for instance a Bio-Gideâ patch is sewn as apatch covering a cartilage defect the porous surface shall be facing down towards the defectin which the cultured chondrocytes are to be injected. They will then be able to penetratethe collagen and produce a smooth cartilage surface in line with the intact surface, and inthis area a smooth layer of proteoglyeans will be built up. Whereas, if the dense surface ofl21015202530CA 02264138 1999-02-26WO 98/08469 PCTIU S97/ 15258the collagen is facing down into the defect the chondrocytes to be implanted will notintegrate with the collagen, and the cells will not produce the same smooth surface asdescribed above.Example 6Chondrocytes were grown in minimal essential culture medium containing HAMF12 and 15 mM Hepes buffer and 5 to 7.5% autologous serum in a CO: incubator at 37°Cand handled in a Class 100 laboratory at Verigen Europe A/S, Symbion Science Park,Copenhagen, Denmark. The cells were trypsinized using trypsin EDTA for 5 to 10 minutesand counted using Trypan Blue viability staining in a Bï¬rker-Tiirk chamber. The cell countwas adjusted to 7.5 x 10â to 2 x 10° cells per ml. One NUNCLONTâ plate was uncovered inthe Class 100 laboratory.The Bio-Gideâ used as a resorbable bilayer membrane may also be used togetherwith an organic glue such as Tisseelqâ with additional, signiï¬cantly higher content ofAprotinin than normally found in Tisseelâ°, as described in the product insert. By increasingthe content of Aprotinin to about 25,000 KIU/ml, the resorption of the material will bedelayed by weeks instead of the normal span of days.To test this feature in vitro, the Tisseelâ is applied to the bottom of the well of theNUNCLONTâ plate, and allowed to solidify incompletely. A collagen patch such as a Bio-Gide® is then applied over the Tisseel® and glued to the bottom of the well. Thiscombination of Bio-Gideâ and Tisseelâ is designed to be a hcmostatic barrier that willinhibit or prevent development or infiltration of blood vessels into the chondrocytctransplantation area. This hybrid collagen patch can now be used for both as a hemostaticbarrier at the bottom of the lesion (most proximal to the surface to be repaired) but also as asupport for cartilage formation because the distal surface can be the porous side of thecollagen patch and thus encourage infiltration of chondrocytes and cartilage matrix. Thusthis hybrid collagen patch can also be used to cover the top of the implant with the collagenporous surface directed down towards the implanted chondrocytes and the barrier formingthe top. The hybrid collagen patch, with elevated Aprotinin component may also be usedwithout any organic glue such as Tisseel° and placed within the defect directly, adhering bynatural forces. Thus the collagen patch can be used both as the hcmostatic barrier, and thecell-free covering of the repair/transplant site, with the porous surfaces of the patchesoriented towards the transplanted chondrocytes/cartilage. Another variant would use a1310l5202530CA 02264138 1999-02-26wo 93/03459 PCT/US97l15258collagen patch which consists of type II collagen (ie. from Geistlich Sohne AG, CHâ6l 10Wolhusen).Thus the instant invention provides for a hybrid collagen patch where said patch is acollagen matrix with elevated levels of aprotinin component, preferably about 25,000KIU/ml, in association with an organic matrix glue, where the collagen component issimilar to the Bio-Gideâ resorbable bilayer material or Type II collagen, and the organicglue is similar to the Tisseel° material. In another embodiment, the hybrid collagen patchdoes not use any organic glue to adhere to the site of the repair.Example 7Because of the weakened structure of osteoarthiitie cartilage, adherence of culturedautologous chondrocytes transplanted to a graft site in defective cartilage may be inhibited,thus creating a marginal zone (zone of demarcation) between the newly implantedcartilage/chondrocytes and the surrounding established cartilage. This marginal zone will bemost pronounced if the graï¬ site is prepared for the graft by creating straight, smooth wallscut in a linear fashion. The shearing and compression forces across such a marginal zone (asillustrated in Figure 3A) will exert great force to dislodge the graft when the graft site is cutin a linear fashion. This marginal zone, and differential movement of materials along thiszone will inhibit confluent healing between the grafted material and the surroundingmaterial. This marginal zone shearing is exacerbated when the hardness of the abuttingmaterial is different. In many cases the graft material is softer than the surroundingmaterial, however, in some instances of osteoarthritis disease, the surrounding cartilagemay in fact be softer than the implanted chondrocytes/cartilage.Therefore, in order to solve this problem, the method of the invention teaches theuse of surgical instruments to sculpt the walls of the graft site such that the walls are non-linear, and thus provide for undulated surfaces which will reduce marginal zone shearingand provide anchorage for grafted material. It is also possible to shape the graft site suchthat the diameter of the site proximal to the bone surface is of a greater dimension then theopening distal to the bone and at the surface of the cartilage to be repaired such that there isa âreverse funnelâ effect. A narrowed opening at the surface will aid in reducing marginalzone shearing and the expulsion of graï¬ material from the graft site. A preferredembodiment describes the sculpting of the walls of the graft site in an fashion similar to athreaded opening for receiving a belt or screw (as illustrated in Figure 3B), thus providingl4I0202530CA 02264138 1999-02-26WO 98/08469 PCTIUS97l15258mechanical resistance to the compression and or ejection of the grafted material from thegraft site which can be described as âmaleâ and âfemaleâ threading.The surgical instruments contemplated by the instant invention can be manufacturedï¬'om metal and/or plastic suitable for making singleâuse disposable, or multi-use reusablesurgical instruments. As cartilage is a relatively soft material it may be advantageous tomanufacture hardened plastic cutting edges which will be able to sculpt cartilage withoutbeing able to damage bone. Such cutting instruments can be manufactured to incorporateopenings for administration of ï¬uid, suction removal of cutting debris and ï¬uid, and ï¬beroptic threads for illumination and visualization of the defect site. In certain embodiments ofthe instrument, the base of the instrument may have protruding point or pin-like structurewhich will assist in guiding and placing the instrument in the graft site. Of course such a pinwould be designed to minimized damage to the underlying bone.While the cutting surface of the instrument may be single toothed. or multi-toothed,or describe a screw-like pattern such as that in a metal tap used to generate threaded holesin metal parts, the characteristic required of the cutting instrument is that the resultingsculpted sides of the graft site is undulated, and non-linear. For example, in certainembodiments, the cutting edge of the instrument can be shaped similar to that shown inFigure 4A, or as in Figure 4B. The cutting edge maybe ï¬at, or circular in that it wrapsaround the diameter of the cutting instrument. Many other shapes can be designed toaccomplish the purpose of the method of the invention to create an interface which providesfor mechanical resistance to differential reaction to compression and shearing forces on thetransplanted material and the surrounding material.Example 8A four month old mixed Yorkshire breed pig was subjected to general anesthesiaand placed on its back. The pig was washed and draped in a surgical suite at HarringtonArthritis Research Center, Phoenix, Arizona. The entire surgical procedure was performedaseptically. The left hind-leg and adjacent abdomen and inguinal area was cleaned withiodine. The knee joint was localized, and the patella localized. A medial incision wasperformed approximately 3 cm from the posterior part of the patella and the severalsubcutis, muscle layers and ligaments was cut approximately in order to get access to themedial femoral condyle. Using a circular cutter a lesion was prepared in the white cartilageon the medial part of the medial condylc, leaving a 0.5 to 1 cm margin to the edge of theISl015202530CA 02264138 1999-02-26W0 98108469 PCTIUS97/1 5258cartilage covering the posterior-medial part of the condylc (left condyle, Figure 6A). The0.5 to 1 cm defect was placed in a caudal weight bearing part of the medial condyle. Theentire surgical procedure was done without tourniquet on the left femur. The different layersand skin was sutured appropriately.On day 3 the animal was again brought to the surgical suite and positioned as aboveon the operating table and given general anesthesia. The left hind leg, abdomen andinguinal region was ionized as described above. Sutures were cut and the area opened. Itwas noticed that a moderate hematoma was present in the knee joint. The blood clot wasremoved and the defect inspected. There was a blood clot in the defect which was removed.A sterile surgical instrument designed with a male thread cutting edge, with a sizecorresponding to, or slightly bigger than the circumference of the lesion was carefullyscrewed down into the defect. A BioGide°â pad was cut to a size equal to the bottom of thedefect. The first glue used. called Adhesive Protein (A-2707, Sigma Chemical, USA) wasapplied on the dense side of the trimmed hemostatic barrier pad, and the pad was placeddense side down into the bottom of the lesion, using it as a barrier as described above. Itwas found that this glue did not seem to dry very fast. The slight bleeding from the bottomof the defect stopped immediately. A second BioGide" was cut somewhat bigger incircumference than the lesion and was placed with dense side up (thus the porous side downtowards the graft) as described above.This nonâcellular covering-pad was then sutured over the cavity, leaving one edgeopen, where the chondrocyte to be explanted could be injected into the graft site. Thesurrounding part of the edge of the pad was covered with the second glue, Dow CorningMedical Adhesive B (Cat. #895-3, Dow Corning, USA). This second glue dried much fasterand more efficiently than the first glue. It was found that during this particular procedure,the ï¬rst glue had not dried sufficiently to hold the hemostatic barrier in place when suturingof the cap was attempted. The main barrier formed on the proximal surface of the graft sitewas by the glue itself.Using a 1 ml syringe and a 16 gauge needle. the chondrocyte cell suspension (about0.6 ml) was drawn up into the barrel of the syringe. A 23 gauge short needle was switchedfor the 16 gauge needle, and the cell suspension was injected under the sutured covering-patch into the graft site (about 10 x 10° cells). The open edge of the cap was then gluedprior to removal of the needle, and the needle carefully withdrawn. No leakage of cells wasseen. The wound was sutured and as above, no tourniquet was used, no bleeding wasl61015202530CA 02264138 1999-02-26WO 98/08469 PCT IU S97/15258observed. The final skin layers were sutured. No protrusion of the skin occurred aftersuturing, which indicates that there was no hematoma. Postoperative recovery wasuneventful.As expected, the grafted chondrocytes produced cartilage matrix sufï¬cient to repairthe defect made in the articular cartilage surface of the knee joint of the test pig. Figure 6Ais an MRI image of a pig knee showing the cartilage defect created in the knee (leftcondyle, the medial condyle), and Figure 6B is an MRI image of the same pig knee threemonths after treatment showing repair of the defect.Example 9A kit comprising the components useful for practicing the method of the invention,will allow for the convenient practice of the method of the invention in a surgical setting. Ina preferred embodiment, a kit of the invention will provide sterile components suitable foreasy use in the surgical environment, and will provide a suitable hemostatic barrier, suitablecovering patch, and if needed organic glue. A kit of the invention may also provide sterile,cellâfree matrix material suitable for supporting autologous chondrocytes that are to beimplanted into an articular joint surface defect. In one embodiment, a kit of the inventioncontains a Surgicel° hemostatic barrier and a Bio-Gideâ covering patch with suitablecoating of Tisseel"° organic glue, where the Surgicel° and Bio-Gideâ have been treatedaccording to the teachings of the invention to increase the time till resorption. In instanceswhere Tisseel® is preâcoated, in one embodiment the 'lâisseel® is supplemented withadditional aprotinin to increase time till resorption.In another preferred embodiment, the hemostatic barrier and covering-patch are botha semi-permeable collagen matrix which is treated to extend the time till resorption of thematerial. It is also possible to provide 'Iâisseelââ glue in enhanced form as a separatecomponent to be applied as needed because of the inherent variability and uniquecircumstances every repair/transplantation procedure will encounter.A further embodiment of a kit of the invention will include a surgical instrument asdescribed in Example 7 above, or suitable variations thereof.It will be appreciated by persons skilled in the art that numerous variations and/ormodifications may be made to the invention shown in the specific embodiments withoutdeparting form the spirit and scope of the invention as described.
Claims (14)
OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A cartilage repair structure for repair of a defect in articular cartilage comprising:
a cell-free membrane, said membrane having a porous surface and a dense surface; and chondrocyte cells adjacent said porous surface of said membrane.
a cell-free membrane, said membrane having a porous surface and a dense surface; and chondrocyte cells adjacent said porous surface of said membrane.
2. A cartilage repair structure according to claim 1, wherein said chondrocyte cells are adhered to said porous surface.
3. A cartilage repair structure according to claim 2, wherein said cells are grown on said porous surface.
4. A cartilage repair structure according to claim 1, wherein said membrane is collagen.
5. A cartilage repair structure according to claim 1, wherein said membrane is Type I and Type III collagen.
6. A cartilage repair structure according to claim 1, wherein said membrane is resorbable.
7. A cartilage repair structure according to claim 1, wherein said chondrocyte cells are autologous.
8. A cartilage repair structure according to claim 1, wherein said chondrocyte cells are allogenic.
9. A cartilage repair structure according to claim l, wherein said chondrocytes are xenogenic.
10. A cartilage repair structure according to claim 1, further comprising biocompatible adhesive adjacent said membrane.
11. A cartilage repair structure according to claim 1, wherein said membrane is adapted to be disposed over the articular cartilage defect.
12. A cartilage repair structure according to claim 1, wherein said membrane is adapted to be disposed in the articular cartilage defect.
13. A cartilage repair structure according to claim 1, wherein said membrane is disposed over the articular cartilage defect.
14. A cartilage repair structure according to claim 1, wherein said membrane is disposed in the articular cartilage defect.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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CA002419644A CA2419644C (en) | 1996-08-30 | 1997-08-29 | Method and kit for the transplantation of chondrocyte cells |
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
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US08/704,891 US5759190A (en) | 1996-08-30 | 1996-08-30 | Method and kit for autologous transplantation |
US08/704,891 | 1996-08-30 | ||
US08/857,090 | 1997-05-15 | ||
US08/857,090 US5989269A (en) | 1996-08-30 | 1997-05-15 | Method, instruments and kit for autologous transplantation |
PCT/US1997/015258 WO1998008469A2 (en) | 1996-08-30 | 1997-08-29 | Method, instruments and kit for autologous transplantation |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
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CA002419644A Division CA2419644C (en) | 1996-08-30 | 1997-08-29 | Method and kit for the transplantation of chondrocyte cells |
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CA2264138C true CA2264138C (en) | 2003-05-27 |
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CA002264138A Expired - Lifetime CA2264138C (en) | 1996-08-30 | 1997-08-29 | Method, instruments and kit for autologous transplantation |
CA002419644A Expired - Lifetime CA2419644C (en) | 1996-08-30 | 1997-08-29 | Method and kit for the transplantation of chondrocyte cells |
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CA002419644A Expired - Lifetime CA2419644C (en) | 1996-08-30 | 1997-08-29 | Method and kit for the transplantation of chondrocyte cells |
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Families Citing this family (205)
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 |
US5940807A (en) * | 1996-05-24 | 1999-08-17 | Purcell; Daniel S. | Automated and independently accessible inventory information exchange system |
US20020173806A1 (en) * | 1996-08-30 | 2002-11-21 | Verigen Transplantation Service International (Vtsi) Ag | Method for autologous transplantation |
US6569172B2 (en) * | 1996-08-30 | 2003-05-27 | Verigen Transplantation Service International (Vtsi) | Method, instruments, and kit for autologous transplantation |
US20060025786A1 (en) * | 1996-08-30 | 2006-02-02 | Verigen Transplantation Service International (Vtsi) Ag | Method for autologous transplantation |
US5989269A (en) * | 1996-08-30 | 1999-11-23 | Vts Holdings L.L.C. | Method, instruments and kit for autologous transplantation |
US9603711B2 (en) | 2001-05-25 | 2017-03-28 | Conformis, Inc. | Patient-adapted and improved articular implants, designs and related guide tools |
US8480754B2 (en) | 2001-05-25 | 2013-07-09 | Conformis, Inc. | Patient-adapted and improved articular implants, designs and related guide tools |
US8545569B2 (en) | 2001-05-25 | 2013-10-01 | Conformis, Inc. | Patient selectable knee arthroplasty devices |
US7618451B2 (en) | 2001-05-25 | 2009-11-17 | Conformis, Inc. | Patient selectable joint arthroplasty devices and surgical tools facilitating increased accuracy, speed and simplicity in performing total and partial joint arthroplasty |
US8771365B2 (en) | 2009-02-25 | 2014-07-08 | Conformis, Inc. | Patient-adapted and improved orthopedic implants, designs, and related tools |
US8556983B2 (en) | 2001-05-25 | 2013-10-15 | Conformis, Inc. | Patient-adapted and improved orthopedic implants, designs and related tools |
US8617242B2 (en) | 2001-05-25 | 2013-12-31 | Conformis, Inc. | Implant device and method for manufacture |
US7534263B2 (en) | 2001-05-25 | 2009-05-19 | Conformis, Inc. | Surgical tools facilitating increased accuracy, speed and simplicity in performing joint arthroplasty |
US8882847B2 (en) | 2001-05-25 | 2014-11-11 | Conformis, Inc. | Patient selectable knee joint arthroplasty devices |
US10085839B2 (en) | 2004-01-05 | 2018-10-02 | Conformis, Inc. | Patient-specific and patient-engineered orthopedic implants |
US20070100462A1 (en) | 2001-05-25 | 2007-05-03 | Conformis, Inc | Joint Arthroplasty Devices |
US8234097B2 (en) | 2001-05-25 | 2012-07-31 | Conformis, Inc. | Automated systems for manufacturing patient-specific orthopedic implants and instrumentation |
US7468075B2 (en) | 2001-05-25 | 2008-12-23 | Conformis, Inc. | Methods and compositions for articular repair |
US8735773B2 (en) | 2007-02-14 | 2014-05-27 | Conformis, Inc. | Implant device and method for manufacture |
US8083745B2 (en) | 2001-05-25 | 2011-12-27 | Conformis, Inc. | Surgical tools for arthroplasty |
US20030180263A1 (en) * | 2002-02-21 | 2003-09-25 | Peter Geistlich | Resorbable extracellular matrix for reconstruction of bone |
US20050186283A1 (en) * | 1997-10-10 | 2005-08-25 | Ed. Geistlich Soehne Ag Fuer Chemistrie Industrie | Collagen carrier of therapeutic genetic material, and method |
US8858981B2 (en) * | 1997-10-10 | 2014-10-14 | Ed. Geistlich Soehne Fuer Chemistrie Industrie | Bone healing material comprising matrix carrying bone-forming cells |
US9034315B2 (en) * | 1997-10-10 | 2015-05-19 | Ed. Geistlich Soehne Ag Fuer Chemische Industrie | Cell-charged multi-layer collagen membrane |
US8563232B2 (en) | 2000-09-12 | 2013-10-22 | Lifenet Health | Process for devitalizing soft-tissue engineered medical implants, and devitalized soft-tissue medical implants produced |
US20080077251A1 (en) * | 1999-06-07 | 2008-03-27 | Chen Silvia S | Cleaning and devitalization of cartilage |
US6293970B1 (en) | 1998-06-30 | 2001-09-25 | Lifenet | Plasticized bone and soft tissue grafts and methods of making and using same |
US20100030340A1 (en) * | 1998-06-30 | 2010-02-04 | Wolfinbarger Jr Lloyd | Plasticized Grafts and Methods of Making and Using Same |
TR200100482T2 (en) * | 1998-08-14 | 2001-06-21 | Verigen Transplantation Service International(Vtsi)Ag | Methods for chondrocyte cell transplantation; instruments and items |
EP1656960A1 (en) * | 1998-08-14 | 2006-05-17 | Verigen AG | Methods, instruments and materials for chondrocyte cell transplantation |
JP2002532126A (en) | 1998-09-14 | 2002-10-02 | スタンフォード ユニバーシティ | Joint condition evaluation and damage prevention device |
US7239908B1 (en) | 1998-09-14 | 2007-07-03 | The Board Of Trustees Of The Leland Stanford Junior University | Assessing the condition of a joint and devising treatment |
US20020081732A1 (en) | 2000-10-18 | 2002-06-27 | Bowlin Gary L. | Electroprocessing in drug delivery and cell encapsulation |
US7615373B2 (en) | 1999-02-25 | 2009-11-10 | Virginia Commonwealth University Intellectual Property Foundation | Electroprocessed collagen and tissue engineering |
US7476250B1 (en) * | 1999-04-06 | 2009-01-13 | Mansmann Kevin A | Semi-permeable membranes to assist in cartilage repair |
US20020095157A1 (en) | 1999-07-23 | 2002-07-18 | Bowman Steven M. | Graft fixation device combination |
US6179840B1 (en) | 1999-07-23 | 2001-01-30 | Ethicon, Inc. | Graft fixation device and method |
DE60018576T2 (en) * | 1999-07-28 | 2006-04-13 | Interface Biotech A/S | IN VITRO HEALING OF BONE AND / OR TROUBLE DAMAGE |
US20020116063A1 (en) * | 1999-08-02 | 2002-08-22 | Bruno Giannetti | Kit for chondrocyte cell transplantation |
CA2391819A1 (en) * | 1999-08-02 | 2001-02-08 | Verigen Transplantation Service International Ag | Kit for chondrocyte cell transplantation |
EP1233707B1 (en) * | 1999-12-03 | 2007-08-08 | The University Of Leeds | Repair of damaged tissue |
US6626945B2 (en) * | 2000-03-14 | 2003-09-30 | Chondrosite, Llc | Cartilage repair plug |
US7678151B2 (en) | 2000-05-01 | 2010-03-16 | Ek Steven W | System and method for joint resurface repair |
AU2001259327B2 (en) * | 2000-05-01 | 2005-02-17 | Arthrosurface, Inc. | System and method for joint resurface repair |
US7713305B2 (en) * | 2000-05-01 | 2010-05-11 | Arthrosurface, Inc. | Articular surface implant |
US6520964B2 (en) * | 2000-05-01 | 2003-02-18 | Std Manufacturing, Inc. | System and method for joint resurface repair |
US6610067B2 (en) | 2000-05-01 | 2003-08-26 | Arthrosurface, Incorporated | System and method for joint resurface repair |
US8177841B2 (en) | 2000-05-01 | 2012-05-15 | Arthrosurface Inc. | System and method for joint resurface repair |
US7163541B2 (en) | 2002-12-03 | 2007-01-16 | Arthrosurface Incorporated | Tibial resurfacing system |
US8366787B2 (en) | 2000-08-04 | 2013-02-05 | Depuy Products, Inc. | Hybrid biologic-synthetic bioabsorbable scaffolds |
US6638312B2 (en) | 2000-08-04 | 2003-10-28 | Depuy Orthopaedics, Inc. | Reinforced small intestinal submucosa (SIS) |
AU2001288692A1 (en) | 2000-09-01 | 2002-03-13 | Virginia Commonwealth University Intellectual Property Foundation | Electroprocessed fibrin-based matrices and tissues |
EP1322224B1 (en) | 2000-09-14 | 2008-11-05 | The Board Of Trustees Of The Leland Stanford Junior University | Assessing condition of a joint and cartilage loss |
WO2002022014A1 (en) | 2000-09-14 | 2002-03-21 | The Board Of Trustees Of The Leland Stanford Junior University | Assessing the condition of a joint and devising treatment |
US6852330B2 (en) * | 2000-12-21 | 2005-02-08 | Depuy Mitek, Inc. | Reinforced foam implants with enhanced integrity for soft tissue repair and regeneration |
US20020127265A1 (en) * | 2000-12-21 | 2002-09-12 | Bowman Steven M. | Use of reinforced foam implants with enhanced integrity for soft tissue repair and regeneration |
CA2365376C (en) | 2000-12-21 | 2006-03-28 | Ethicon, Inc. | Use of reinforced foam implants with enhanced integrity for soft tissue repair and regeneration |
US6599323B2 (en) * | 2000-12-21 | 2003-07-29 | Ethicon, Inc. | Reinforced tissue implants and methods of manufacture and use |
US20040151705A1 (en) * | 2002-03-22 | 2004-08-05 | Shuichi Mizuno | Neo-cartilage constructs and a method for preparation thereof |
US6713085B2 (en) | 2001-04-27 | 2004-03-30 | Ed. Geistlich Soehne Ag Fuer Chemische Industrie | Method and membrane for mucosa regeneration |
US8951260B2 (en) | 2001-05-25 | 2015-02-10 | Conformis, Inc. | Surgical cutting guide |
AU2002310193B8 (en) | 2001-05-25 | 2007-05-17 | Conformis, Inc. | Methods and compositions for articular resurfacing |
US8439926B2 (en) | 2001-05-25 | 2013-05-14 | Conformis, Inc. | Patient selectable joint arthroplasty devices and surgical tools |
US6723102B2 (en) * | 2001-06-14 | 2004-04-20 | Alexandria Research Technologies, Llc | Apparatus and method for minimally invasive total joint replacement |
US6482209B1 (en) * | 2001-06-14 | 2002-11-19 | Gerard A. Engh | Apparatus and method for sculpting the surface of a joint |
AU2002322567B2 (en) | 2001-07-16 | 2007-09-06 | Depuy Products, Inc. | Devices form naturally occurring biologically derived |
WO2003007787A2 (en) | 2001-07-16 | 2003-01-30 | Depuy Products, Inc. | Cartilage repair and regeneration device and method |
WO2003007786A2 (en) | 2001-07-16 | 2003-01-30 | Depuy Products, Inc. | Porous delivery scaffold and method |
US8025896B2 (en) | 2001-07-16 | 2011-09-27 | Depuy Products, Inc. | Porous extracellular matrix scaffold and method |
US7361195B2 (en) | 2001-07-16 | 2008-04-22 | Depuy Products, Inc. | Cartilage repair apparatus and method |
EP1416879A4 (en) * | 2001-07-16 | 2007-04-25 | Depuy Products Inc | Unitary surgical device and method |
EP1416888A4 (en) | 2001-07-16 | 2007-04-25 | Depuy Products Inc | Meniscus regeneration device and method |
US7819918B2 (en) | 2001-07-16 | 2010-10-26 | Depuy Products, Inc. | Implantable tissue repair device |
US7914808B2 (en) | 2001-07-16 | 2011-03-29 | Depuy Products, Inc. | Hybrid biologic/synthetic porous extracellular matrix scaffolds |
CN1592635A (en) * | 2001-09-24 | 2005-03-09 | 维里根股份公司 | Autologous growth factor cocktail composition, method of production and use |
JP4330991B2 (en) * | 2001-10-01 | 2009-09-16 | スキャンディウス・バイオメディカル・インコーポレーテッド | Apparatus and method for repairing articular cartilage defects |
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 |
BR0307033A (en) * | 2002-01-22 | 2004-12-07 | Pfizer | 3- (imidazolyl) -2-aminopropanoic acids for use as tafi-a inhibitors for the treatment of thrombotic diseases |
US7537780B2 (en) * | 2002-03-22 | 2009-05-26 | Histogenics Corporation | Method for preparing and implanting a cartilage construct to treat cartilage lesions |
CA2483660A1 (en) * | 2002-05-01 | 2003-11-13 | Verigen Ag | Injectable chondrocyte implant |
SE0201479D0 (en) * | 2002-05-16 | 2002-05-16 | Pharmacia Groningen Bv | Kit and method in eye surgery |
US20040166169A1 (en) * | 2002-07-15 | 2004-08-26 | Prasanna Malaviya | Porous extracellular matrix scaffold and method |
US20040136968A1 (en) * | 2002-09-27 | 2004-07-15 | Verigen Ag | Autologous cells on a support matrix for tissue repair |
ATE497740T1 (en) * | 2002-10-07 | 2011-02-15 | Conformis Inc | MINIMALLY INVASIVE JOINT IMPLANT WITH A THREE-DIMENSIONAL GEOMETRY ADAPTED TO THE JOINT SURFACES |
US20040078090A1 (en) | 2002-10-18 | 2004-04-22 | Francois Binette | Biocompatible scaffolds with tissue fragments |
US7824701B2 (en) | 2002-10-18 | 2010-11-02 | Ethicon, Inc. | Biocompatible scaffold for ligament or tendon repair |
US7799084B2 (en) | 2002-10-23 | 2010-09-21 | Mako Surgical Corp. | Modular femoral component for a total knee joint replacement for minimally invasive implantation |
EP3075356B1 (en) | 2002-11-07 | 2023-07-05 | ConforMIS, Inc. | Method of selecting a meniscal implant |
US20060147332A1 (en) | 2004-12-30 | 2006-07-06 | Howmedica Osteonics Corp. | Laser-produced porous structure |
EP1418013B1 (en) | 2002-11-08 | 2005-01-19 | Howmedica Osteonics Corp. | Laser-produced porous surface |
US7901408B2 (en) | 2002-12-03 | 2011-03-08 | Arthrosurface, Inc. | System and method for retrograde procedure |
AU2003900620A0 (en) * | 2003-02-12 | 2003-02-27 | Australian Surgical Design And Manufacture Pty Limited | Arthroscopic chondrocyte implantation method and device |
US8388624B2 (en) | 2003-02-24 | 2013-03-05 | Arthrosurface Incorporated | Trochlear resurfacing system and method |
US8197837B2 (en) | 2003-03-07 | 2012-06-12 | Depuy Mitek, Inc. | Method of preparation of bioabsorbable porous reinforced tissue implants and implants thereof |
US7067123B2 (en) | 2003-04-29 | 2006-06-27 | Musculoskeletal Transplant Foundation | Glue for cartilage repair |
US20050064042A1 (en) * | 2003-04-29 | 2005-03-24 | Musculoskeletal Transplant Foundation | Cartilage implant plug with fibrin glue and method for implantation |
US7488348B2 (en) | 2003-05-16 | 2009-02-10 | Musculoskeletal Transplant Foundation | Cartilage allograft plug |
US7901457B2 (en) | 2003-05-16 | 2011-03-08 | Musculoskeletal Transplant Foundation | Cartilage allograft plug |
CA2528399A1 (en) * | 2003-06-12 | 2004-12-23 | Interface Biotech A/S | A method for cell implantation |
US8226715B2 (en) | 2003-06-30 | 2012-07-24 | Depuy Mitek, Inc. | Scaffold for connective tissue repair |
US10583220B2 (en) | 2003-08-11 | 2020-03-10 | DePuy Synthes Products, Inc. | Method and apparatus for resurfacing an articular surface |
US20050046915A1 (en) * | 2003-08-22 | 2005-03-03 | Fuji Photo Film Co., Ltd. | Hologram recording material composition, hologram recording material and hologram recording method |
DE10349722A1 (en) | 2003-10-23 | 2005-06-16 | Beschorner, Katharina, Dr. | Composition for arthritis / arthritis treatment, in particular of joints |
GB0325141D0 (en) * | 2003-10-28 | 2003-12-03 | Xiros Plc | Repair of damaged tissue on a bone site |
US7951163B2 (en) | 2003-11-20 | 2011-05-31 | Arthrosurface, Inc. | Retrograde excision system and apparatus |
WO2005051231A2 (en) | 2003-11-20 | 2005-06-09 | Arthrosurface, Inc. | Retrograde delivery of resurfacing devices |
CA2593182A1 (en) | 2003-11-20 | 2006-07-13 | Arthrosurface, Inc. | System and method for retrograde procedure |
US7316822B2 (en) | 2003-11-26 | 2008-01-08 | Ethicon, Inc. | Conformable tissue repair implant capable of injection delivery |
US7901461B2 (en) | 2003-12-05 | 2011-03-08 | Ethicon, Inc. | Viable tissue repair implants and methods of use |
ATE515245T1 (en) | 2003-12-11 | 2011-07-15 | Isto Technologies Inc | PARTICLE CARTILAGE SYSTEM |
US11395865B2 (en) | 2004-02-09 | 2022-07-26 | DePuy Synthes Products, Inc. | Scaffolds with viable tissue |
EP1576957A1 (en) * | 2004-03-18 | 2005-09-21 | Universiteit Twente | Tissue repair using pluripotent cells |
US8221780B2 (en) | 2004-04-20 | 2012-07-17 | Depuy Mitek, Inc. | Nonwoven tissue scaffold |
US8657881B2 (en) | 2004-04-20 | 2014-02-25 | Depuy Mitek, Llc | Meniscal repair scaffold |
US8137686B2 (en) | 2004-04-20 | 2012-03-20 | Depuy Mitek, Inc. | Nonwoven tissue scaffold |
US7569233B2 (en) * | 2004-05-04 | 2009-08-04 | Depuy Products, Inc. | Hybrid biologic-synthetic bioabsorbable scaffolds |
CA2470463C (en) * | 2004-06-09 | 2012-09-18 | Lornamead Brands, Inc. | Tooth whitening products and methods of making the same |
JP2008504107A (en) | 2004-06-28 | 2008-02-14 | アースロサーフィス・インコーポレーテッド | Joint surface replacement system |
CA2541827C (en) * | 2004-07-30 | 2013-05-14 | Histogenics Corporation | Method for in situ repair of injured, damaged, diseased or aged articular cartilage using neo-cartilage constructs and a method for preparation thereof |
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 |
US7513866B2 (en) | 2004-10-29 | 2009-04-07 | Depuy Products, Inc. | Intestine processing device and associated method |
US20060111778A1 (en) * | 2004-10-29 | 2006-05-25 | Michalow Alexander E | Methods of promoting healing of cartilage defects and method of causing stem cells to differentiate by the articular chondrocyte pathway |
US7828853B2 (en) | 2004-11-22 | 2010-11-09 | Arthrosurface, Inc. | Articular surface implant and delivery system |
US7354627B2 (en) * | 2004-12-22 | 2008-04-08 | Depuy Products, Inc. | Method for organizing the assembly of collagen fibers and compositions formed therefrom |
CN100384390C (en) * | 2005-01-13 | 2008-04-30 | 中国人民解放军第三军医大学第一附属医院 | Complex tissue of tissue-engineered bone and cartilage and external constructing method thereof |
US7815926B2 (en) | 2005-07-11 | 2010-10-19 | Musculoskeletal Transplant Foundation | Implant for articular cartilage repair |
WO2007025290A2 (en) | 2005-08-26 | 2007-03-01 | Isto Technologies, Inc. | Implants and methods for repair, replacement and treatment of joint disease |
EP1924146A4 (en) * | 2005-09-02 | 2012-05-02 | Interface Biotech As | A method for cell implantation |
EP1926459B1 (en) | 2005-09-19 | 2015-01-07 | Histogenics Corporation | Cell-support matrix having narrowly defined uniformly vertically and non-randomly organized porosity and pore density and a method for preparation thereof |
CN101384230A (en) | 2005-11-21 | 2009-03-11 | 福特真公司 | Devices and methods for treating facet joints, uncovertebral joints, costovertebral joints and other joints |
US8728387B2 (en) | 2005-12-06 | 2014-05-20 | Howmedica Osteonics Corp. | Laser-produced porous surface |
EP1803513B1 (en) * | 2005-12-30 | 2017-03-29 | Howmedica Osteonics Corp. | Method of manufacturing implants using laser |
US8623026B2 (en) | 2006-02-06 | 2014-01-07 | Conformis, Inc. | Patient selectable joint arthroplasty devices and surgical tools incorporating anatomical relief |
CN101420911B (en) | 2006-02-06 | 2012-07-18 | 康复米斯公司 | Patient selectable arthroplasty device and surjical tool |
US20070288021A1 (en) * | 2006-06-07 | 2007-12-13 | Howmedica Osteonics Corp. | Flexible joint implant |
US8147861B2 (en) * | 2006-08-15 | 2012-04-03 | Howmedica Osteonics Corp. | Antimicrobial implant |
DE07825069T1 (en) * | 2006-09-07 | 2010-04-08 | Ed Geistlich Söhne Ag Für Chemische Industrie | METHOD FOR THE TREATMENT OF BONE CANCER |
KR20080037883A (en) * | 2006-10-27 | 2008-05-02 | 세원셀론텍(주) | Using method and medical kit |
EP2136717B1 (en) | 2006-12-11 | 2013-10-16 | Arthrosurface Incorporated | Retrograde resection apparatus |
US7871440B2 (en) | 2006-12-11 | 2011-01-18 | Depuy Products, Inc. | Unitary surgical device and method |
US8163549B2 (en) | 2006-12-20 | 2012-04-24 | Zimmer Orthobiologics, Inc. | Method of obtaining viable small tissue particles and use for tissue repair |
US7758643B2 (en) * | 2007-02-26 | 2010-07-20 | Biomet Sports Medicine, Llc | Stable cartilage defect repair plug |
US8435551B2 (en) | 2007-03-06 | 2013-05-07 | Musculoskeletal Transplant Foundation | Cancellous construct with support ring for repair of osteochondral defects |
WO2008128075A1 (en) | 2007-04-12 | 2008-10-23 | Isto Technologies, Inc. | Compositions and methods for tissue repair |
US8685107B2 (en) | 2007-07-03 | 2014-04-01 | Histogenics Corporation | Double-structured tissue implant and a method for preparation and use thereof |
US20090054984A1 (en) | 2007-08-20 | 2009-02-26 | Histogenics Corporation | Method For Use Of A Double-Structured Tissue Implant For Treatment Of Tissue Defects |
US9125743B2 (en) * | 2007-07-16 | 2015-09-08 | Lifenet Health | Devitalization and recellularization of cartilage |
US20090024224A1 (en) | 2007-07-16 | 2009-01-22 | Chen Silvia S | Implantation of cartilage |
WO2009014718A1 (en) | 2007-07-24 | 2009-01-29 | Porex Corporation | Porous laser sintered articles |
WO2009026392A1 (en) | 2007-08-20 | 2009-02-26 | Histogenics Corporation | A method for improvement of differentiation of mesenchymal stem cells using a double-structured tissue implant |
CA2701884A1 (en) * | 2007-10-15 | 2009-04-23 | Wake Forest University Health Sciences | Methods and compositions for printing biologically compatible nanotube composites of autologous tissue |
EP2291205A2 (en) * | 2008-02-29 | 2011-03-09 | Coloplast A/S | Compositions and methods for augmentation and regeneration of living tissue in a subject |
CA2713118A1 (en) * | 2008-02-29 | 2009-09-03 | Interface Biotech A/S | Biosynthetic cartilaginous matrix and methods for their production |
WO2009111481A1 (en) | 2008-03-03 | 2009-09-11 | Arthrosurface Incorporated | Bone resurfacing system and method |
EP2265220A1 (en) | 2008-03-05 | 2010-12-29 | Musculoskeletal Transplant Foundation | Cancellous constructs, cartilage particles and combinations of cancellous constructs and cartilage particles |
WO2009111626A2 (en) | 2008-03-05 | 2009-09-11 | Conformis, Inc. | Implants for altering wear patterns of articular surfaces |
JP2011519713A (en) | 2008-05-12 | 2011-07-14 | コンフォーミス・インコーポレイテッド | Devices and methods for treatment of facet joints and other joints |
GB0812631D0 (en) * | 2008-07-10 | 2008-08-20 | Imp Innovations Ltd | Modular knee implants |
US8808297B2 (en) | 2009-02-24 | 2014-08-19 | Microport Orthopedics Holdings Inc. | Orthopedic surgical guide |
US9017334B2 (en) | 2009-02-24 | 2015-04-28 | Microport Orthopedics Holdings Inc. | Patient specific surgical guide locator and mount |
US8808303B2 (en) | 2009-02-24 | 2014-08-19 | Microport Orthopedics Holdings Inc. | Orthopedic surgical guide |
JP2012523897A (en) | 2009-04-16 | 2012-10-11 | コンフォーミス・インコーポレイテッド | Patient-specific joint replacement device for ligament repair |
US9662126B2 (en) | 2009-04-17 | 2017-05-30 | Arthrosurface Incorporated | Glenoid resurfacing system and method |
WO2010121246A1 (en) | 2009-04-17 | 2010-10-21 | Arthrosurface Incorporated | Glenoid resurfacing system and method |
WO2016154393A1 (en) | 2009-04-17 | 2016-09-29 | Arthrosurface Incorporated | Glenoid repair system and methods of use thereof |
AU2011222404A1 (en) | 2010-03-05 | 2012-09-27 | Arthrosurface Incorporated | Tibial resurfacing system and method |
US8895291B2 (en) | 2010-10-08 | 2014-11-25 | Terumo Bct, Inc. | Methods and systems of growing and harvesting cells in a hollow fiber bioreactor system with control conditions |
EP2754419B1 (en) | 2011-02-15 | 2024-02-07 | ConforMIS, Inc. | Patient-adapted and improved orthopedic implants |
US9066716B2 (en) | 2011-03-30 | 2015-06-30 | Arthrosurface Incorporated | Suture coil and suture sheath for tissue repair |
WO2013081071A1 (en) * | 2011-12-02 | 2013-06-06 | テルモ株式会社 | Device for cell transplantation |
EP2804565B1 (en) | 2011-12-22 | 2018-03-07 | Arthrosurface Incorporated | System for bone fixation |
US9364896B2 (en) | 2012-02-07 | 2016-06-14 | Medical Modeling Inc. | Fabrication of hybrid solid-porous medical implantable devices with electron beam melting technology |
US9180010B2 (en) | 2012-04-06 | 2015-11-10 | Howmedica Osteonics Corp. | Surface modified unit cell lattice structures for optimized secure freeform fabrication |
US9135374B2 (en) | 2012-04-06 | 2015-09-15 | Howmedica Osteonics Corp. | Surface modified unit cell lattice structures for optimized secure freeform fabrication |
US9486226B2 (en) | 2012-04-18 | 2016-11-08 | Conformis, Inc. | Tibial guides, tools, and techniques for resecting the tibial plateau |
US9186053B2 (en) * | 2012-05-03 | 2015-11-17 | Covidien Lp | Methods of using light to repair hernia defects |
US9675471B2 (en) | 2012-06-11 | 2017-06-13 | Conformis, Inc. | Devices, techniques and methods for assessing joint spacing, balancing soft tissues and obtaining desired kinematics for joint implant components |
US9468448B2 (en) | 2012-07-03 | 2016-10-18 | Arthrosurface Incorporated | System and method for joint resurfacing and repair |
US10016527B2 (en) | 2012-10-23 | 2018-07-10 | Orthovita, Inc. | Materials and methods for repair of cartilage defects |
US20140178343A1 (en) | 2012-12-21 | 2014-06-26 | Jian Q. Yao | Supports and methods for promoting integration of cartilage tissue explants |
US9492200B2 (en) | 2013-04-16 | 2016-11-15 | Arthrosurface Incorporated | Suture system and method |
PL2853384T3 (en) * | 2013-09-27 | 2017-06-30 | Skulle Implants Oy | A method for coating and a coated surface |
EP3068867B1 (en) | 2013-11-16 | 2018-04-18 | Terumo BCT, Inc. | Expanding cells in a bioreactor |
US10624748B2 (en) | 2014-03-07 | 2020-04-21 | Arthrosurface Incorporated | System and method for repairing articular surfaces |
US20150250472A1 (en) | 2014-03-07 | 2015-09-10 | Arthrosurface Incorporated | Delivery System for Articular Surface Implant |
US11607319B2 (en) | 2014-03-07 | 2023-03-21 | Arthrosurface Incorporated | System and method for repairing articular surfaces |
JP6783143B2 (en) | 2014-03-25 | 2020-11-11 | テルモ ビーシーティー、インコーポレーテッド | Passive replenishment of medium |
US20160090569A1 (en) | 2014-09-26 | 2016-03-31 | Terumo Bct, Inc. | Scheduled Feed |
US10077420B2 (en) | 2014-12-02 | 2018-09-18 | Histogenics Corporation | Cell and tissue culture container |
CA2985398C (en) * | 2015-05-08 | 2021-08-03 | Reoss Gmbh | Device for covering and/or reconstructing a bone defect site; method for producing a cap of a covering device for a bone defect site |
US20160331539A1 (en) * | 2015-05-12 | 2016-11-17 | Elwha Llc | Modifiable implants |
WO2017004592A1 (en) | 2015-07-02 | 2017-01-05 | Terumo Bct, Inc. | Cell growth with mechanical stimuli |
US11104874B2 (en) | 2016-06-07 | 2021-08-31 | Terumo Bct, Inc. | Coating a bioreactor |
US11685883B2 (en) | 2016-06-07 | 2023-06-27 | Terumo Bct, Inc. | Methods and systems for coating a cell growth surface |
US11624046B2 (en) | 2017-03-31 | 2023-04-11 | Terumo Bct, Inc. | Cell expansion |
EP3656841A1 (en) | 2017-03-31 | 2020-05-27 | Terumo BCT, Inc. | Cell expansion |
AU2018203479A1 (en) | 2017-05-18 | 2018-12-06 | Howmedica Osteonics Corp. | High fatigue strength porous structure |
WO2019028344A1 (en) | 2017-08-04 | 2019-02-07 | Arthrosurface Incorporated | Multicomponent articular surface implant |
GB2567173A (en) * | 2017-10-04 | 2019-04-10 | Univ Oxford Innovation Ltd | Cartilage plug |
DE102018113580A1 (en) * | 2018-06-07 | 2019-12-12 | Christoph Karl | METHOD AND DEVICE FOR PRODUCING AN IMPLANT |
GB2609338B (en) | 2019-03-12 | 2023-06-14 | Arthrosurface Inc | Humeral and glenoid articular surface implant systems and methods |
US11523834B1 (en) | 2022-06-20 | 2022-12-13 | University Of Utah Research Foundation | Cartilage and bone harvest and delivery system and methods |
US11660194B1 (en) | 2022-06-20 | 2023-05-30 | University Of Utah Research Foundation | Cartilage and bone harvest and delivery system and methods |
Family Cites Families (94)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CH632922A5 (en) | 1978-10-06 | 1982-11-15 | Sulzer Ag | Anchorage pin for bone implants |
ATE4440T1 (en) | 1980-02-21 | 1983-08-15 | J. & P. Coats, Limited | DEVICE FOR TREATMENT OF DAMAGED SURFACES OF HUMAN JOINTS. |
US4649918A (en) * | 1980-09-03 | 1987-03-17 | Custom Medical Devices, Inc. | Bone core removing tool |
US4553272A (en) | 1981-02-26 | 1985-11-19 | University Of Pittsburgh | Regeneration of living tissues by growth of isolated cells in porous implant and product thereof |
US4393874A (en) | 1982-04-26 | 1983-07-19 | Telectronics Pty. Ltd. | Bradycardia event counting and reporting pacer |
IL68218A (en) * | 1983-03-23 | 1985-12-31 | Univ Ramot | Compositions for cartilage repair comprising embryonal chondrocytes |
US4559936A (en) * | 1983-09-29 | 1985-12-24 | Hill Edward B | Bone plugging apparatus |
WO1985001651A1 (en) * | 1983-10-20 | 1985-04-25 | Vettivetpillai Ketharanathan | Biomaterial |
US4620327A (en) | 1984-07-05 | 1986-11-04 | Caplan Arnold I | Process of adapting soluble bone protein for use in stimulating osteoinduction |
US4789663A (en) * | 1984-07-06 | 1988-12-06 | Collagen Corporation | Methods of bone repair using collagen |
US4877020A (en) * | 1984-11-30 | 1989-10-31 | Vich Jose M O | Apparatus for bone graft |
US4642117A (en) | 1985-03-22 | 1987-02-10 | Collagen Corporation | Mechanically sheared collagen implant material and method |
US5902741A (en) | 1986-04-18 | 1999-05-11 | Advanced Tissue Sciences, Inc. | Three-dimensional cartilage cultures |
US5041138A (en) | 1986-11-20 | 1991-08-20 | Massachusetts Institute Of Technology | Neomorphogenesis of cartilage in vivo from cell culture |
US5736372A (en) | 1986-11-20 | 1998-04-07 | Massachusetts Institute Of Technology | Biodegradable synthetic polymeric fibrous matrix containing chondrocyte for in vivo production of a cartilaginous structure |
NL8700113A (en) * | 1987-01-19 | 1988-08-16 | Groningen Science Park | INK, SUITABLE FOR TREATMENT BY RECONSTRUCTIVE SURGERY, WITH TISSUE-SPECIFIC POROSITY, AND METHOD FOR MANUFACTURING THE ENTAGMENT. |
GB8705985D0 (en) | 1987-03-13 | 1987-04-15 | Geistlich Soehne Ag | Dressings |
US4846835A (en) * | 1987-06-15 | 1989-07-11 | Grande Daniel A | Technique for healing lesions in cartilage |
US5306311A (en) * | 1987-07-20 | 1994-04-26 | Regen Corporation | Prosthetic articular cartilage |
US5158574A (en) | 1987-07-20 | 1992-10-27 | Regen Corporation | Prosthetic meniscus |
US5258043A (en) | 1987-07-20 | 1993-11-02 | Regen Corporation | Method for making a prosthetic intervertebral disc |
US5116374A (en) | 1989-03-02 | 1992-05-26 | Regen Corporation | Prosthetic meniscus |
CA1329089C (en) | 1987-09-02 | 1994-05-03 | Russell Warren | Surgical fastener |
NZ226170A (en) | 1987-09-18 | 1990-07-26 | Ethicon Inc | Stable freeze-dried pharmaceutical composition containing epidermal growth factor |
WO1989004646A1 (en) | 1987-11-13 | 1989-06-01 | Jefferies Steven R | Bone repair material and delayed drug delivery |
JP2645098B2 (en) * | 1988-09-06 | 1997-08-25 | テルモ株式会社 | Antibacterial agent-containing artificial skin and method for producing the same |
JP2820415B2 (en) * | 1988-03-14 | 1998-11-05 | ティーエイチエム・バイオメディカル・インコーポレイテッド | Biodegradable and osteogenic graft bone graft substitute composition |
US5201745A (en) * | 1988-03-15 | 1993-04-13 | Imedex | Visceral surgery patch |
US4975526A (en) | 1989-02-23 | 1990-12-04 | Creative Biomolecules, Inc. | Bone collagen matrix for zenogenic implants |
US4904259A (en) * | 1988-04-29 | 1990-02-27 | Samuel Itay | Compositions and methods for repair of cartilage and bone |
US5053050A (en) * | 1988-04-29 | 1991-10-01 | Samuel Itay | Compositions for repair of cartilage and bone |
US5108436A (en) | 1988-09-29 | 1992-04-28 | Collagen Corporation | Implant fixation |
IE61346B1 (en) | 1988-11-02 | 1994-11-02 | Genentech Inc | A permeable material to fit around the teeth or gums of a mammal |
US5162430A (en) | 1988-11-21 | 1992-11-10 | Collagen Corporation | Collagen-polymer conjugates |
US5510418A (en) | 1988-11-21 | 1996-04-23 | Collagen Corporation | Glycosaminoglycan-synthetic polymer conjugates |
US5092883A (en) * | 1988-12-28 | 1992-03-03 | Eppley Barry L | Method for promoting soft connective tissue growth and repair in mammals |
WO1990009783A1 (en) | 1989-02-22 | 1990-09-07 | Massachusetts Institute Of Technology | Delivery system for controlled release of bioactive factors |
AU5654990A (en) | 1989-04-28 | 1990-11-29 | Brigham And Women's Hospital | Novel materials and methods for guided tissue regeneration |
US5015255A (en) * | 1989-05-10 | 1991-05-14 | Spine-Tech, Inc. | Spinal stabilization method |
US5129906A (en) | 1989-09-08 | 1992-07-14 | Linvatec Corporation | Bioabsorbable tack for joining bodily tissue and in vivo method and apparatus for deploying same |
US5067964A (en) * | 1989-12-13 | 1991-11-26 | Stryker Corporation | Articular surface repair |
US5019108A (en) * | 1990-02-02 | 1991-05-28 | Bertin Kim C | Modular implant |
US6413511B1 (en) * | 1990-12-20 | 2002-07-02 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | Cartilage alterations by administering to joints chondrocytes comprising a heterologous polynucleotide |
US5206023A (en) * | 1991-01-31 | 1993-04-27 | Robert F. Shaw | Method and compositions for the treatment and repair of defects or lesions in cartilage |
US5853746A (en) * | 1991-01-31 | 1998-12-29 | Robert Francis Shaw | Methods and compositions for the treatment and repair of defects or lesions in cartilage or bone using functional barrier |
US5206028A (en) | 1991-02-11 | 1993-04-27 | Li Shu Tung | Dense collagen membrane matrices for medical uses |
SE9101853D0 (en) * | 1991-06-17 | 1991-06-17 | Jonas Wadstroem | IMPROVED TISSUE ASHESIVE |
FR2679778B1 (en) | 1991-08-02 | 1995-07-07 | Coletica | USE OF CROLAGEN CROSSLINKED BY A CROSSLINKING AGENT FOR THE MANUFACTURE OF A SLOW RESORPTIVE, BIOCOMPATIBLE, SUTURABLE MEMBRANE, AS WELL AS SUCH A MEMBRANE. |
US5259835A (en) * | 1991-08-29 | 1993-11-09 | Tri-Point Medical L.P. | Wound closure means and method using flowable adhesive |
US5270300A (en) * | 1991-09-06 | 1993-12-14 | Robert Francis Shaw | Methods and compositions for the treatment and repair of defects or lesions in cartilage or bone |
IL100721A (en) * | 1992-01-21 | 1996-12-05 | Milo Simcha | Punch for opening passages between two compartments |
DE69307299T2 (en) * | 1992-02-14 | 1997-04-30 | Univ Texas | MULTI-PHASE, BIODEGRADABLE IMPLANT / CARRIER AND METHOD FOR THE PRODUCTION THEREOF |
US5326357A (en) | 1992-03-18 | 1994-07-05 | Mount Sinai Hospital Corporation | Reconstituted cartridge tissue |
AU4543193A (en) * | 1992-06-22 | 1994-01-24 | Henry E. Young | Scar inhibitory factor and use thereof |
WO1994009118A1 (en) | 1992-10-13 | 1994-04-28 | The General Hospital Corporation | Immortalized human chondrocytes |
US5455597A (en) * | 1992-12-29 | 1995-10-03 | Canon Kabushiki Kaisha | Image-forming apparatus, and designation of electron beam diameter at image-forming member in image-forming apparatus |
DE4300039C1 (en) | 1993-01-04 | 1994-06-09 | Imz Fertigung Vertrieb | Fixture nail for attachment of cover membrane to bone surrounding defect point filled with bone structural material - has nail head of large dia. and shaft of smaller dia. which has cylindrical retention part and conical point part |
US5514378A (en) * | 1993-02-01 | 1996-05-07 | Massachusetts Institute Of Technology | Biocompatible polymer membranes and methods of preparation of three dimensional membrane structures |
DE4431598C2 (en) | 1993-03-03 | 1997-03-20 | Michael Sittinger | Process for producing an implant from cell cultures |
DE4306661C2 (en) | 1993-03-03 | 1995-04-20 | Michael Dipl Biol Sittinger | Process for producing an implant from cell cultures |
US5709854A (en) * | 1993-04-30 | 1998-01-20 | Massachusetts Institute Of Technology | Tissue formation by injecting a cell-polymeric solution that gels in vivo |
DE4317448A1 (en) * | 1993-05-19 | 1994-11-24 | Gross Ulrich | Joint replacement |
CA2130295A1 (en) | 1993-08-26 | 1995-02-27 | Richard A. Berg | Ionically crosslinked glycosaminoglycan gels for soft tissue augmentation and drug delivery |
US5423858A (en) | 1993-09-30 | 1995-06-13 | United States Surgical Corporation | Septoplasty fasteners and device for applying same |
GB9400163D0 (en) | 1994-01-06 | 1994-03-02 | Geistlich Soehne Ag | Membrane |
US5354283A (en) | 1994-01-07 | 1994-10-11 | Little Rapids Corporation | Trocar retention apparatus |
CA2142209A1 (en) | 1994-03-29 | 1995-09-30 | George H. Chu | Collagen implants having improved tensile properties |
WO1995030742A1 (en) * | 1994-05-05 | 1995-11-16 | Genzyme Corporation | Methods and compositions for the repair of articular cartilage defects in mammals |
US5858781A (en) * | 1994-05-13 | 1999-01-12 | Matyas; John R. | Method of tissue transfer and retrieval |
EP0692227A1 (en) | 1994-07-11 | 1996-01-17 | SULZER Medizinaltechnik AG | Sheet implant |
ZA956249B (en) | 1994-07-28 | 1996-05-10 | Ivan Vesely | Bioprosthetic implants and method of making and using same |
US5769899A (en) | 1994-08-12 | 1998-06-23 | Matrix Biotechnologies, Inc. | Cartilage repair unit |
DE4425456A1 (en) * | 1994-09-07 | 1996-03-21 | Matthias Dr Med Honl | Bone saw for concentric cylindrical or part spherical cuts |
US5569252A (en) | 1994-09-27 | 1996-10-29 | Justin; Daniel F. | Device for repairing a meniscal tear in a knee and method |
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 |
US5713374A (en) * | 1995-02-10 | 1998-02-03 | The Hospital For Joint Diseases Orthopaedic Institute | Fixation method for the attachment of wound repair materials to cartilage defects |
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 |
US6132463A (en) * | 1995-05-19 | 2000-10-17 | Etex Corporation | Cell seeding of ceramic compositions |
WO1997004665A1 (en) | 1995-07-31 | 1997-02-13 | Alta Spinner Australia Pty. Limited | Surface moisture removal from food products |
US5659252A (en) * | 1995-08-25 | 1997-08-19 | Sony Corporation | Apparatus and method for detecting arcing in a CRT |
DE19540487A1 (en) | 1995-10-20 | 1997-04-24 | Olaf Schultz | Cell interaction system for induction of artificial 3-dimensional tissue |
WO1997015655A2 (en) | 1995-10-20 | 1997-05-01 | Michael Sittinger | New artificial tissue, method for the production and the use thereof |
DE19601477C2 (en) | 1996-01-17 | 1999-12-16 | Axel Kirsch | Fastening nail |
US5842477A (en) | 1996-02-21 | 1998-12-01 | Advanced Tissue Sciences, Inc. | Method for repairing cartilage |
DE19654884C2 (en) | 1996-03-04 | 1999-07-29 | Kirsch Axel | Molded body |
ES2210526T3 (en) | 1996-06-04 | 2004-07-01 | Centerpulse Biologics Inc. | CARTILAGO PRODUCTION PROCEDURE. |
US5989269A (en) * | 1996-08-30 | 1999-11-23 | Vts Holdings L.L.C. | Method, instruments and kit for autologous transplantation |
EP0842670A1 (en) | 1996-11-13 | 1998-05-20 | Katsunari Nishihara | Biomedical materials |
US6187053B1 (en) | 1996-11-16 | 2001-02-13 | Will Minuth | Process for producing a natural implant |
DE19648876C2 (en) | 1996-11-16 | 1999-10-07 | Will Minuth | Method of making a natural implant |
AU6654598A (en) | 1997-02-13 | 1998-09-08 | Benedict, James A. | Implantable collagen-containing putty material |
DE19957388A1 (en) | 1999-11-24 | 2001-06-13 | Michael Sittinger | Chondroinductive and implantable substrates for cartilage healing and protection |
DE10006822A1 (en) | 2000-02-08 | 2001-08-23 | Michael Sittinger | Artificial bone chips, processes for their production and their use |
-
1997
- 1997-05-15 US US08/857,090 patent/US5989269A/en not_active Expired - Lifetime
- 1997-08-29 PT PT97939677T patent/PT1006950E/en unknown
- 1997-08-29 TR TR1999/00437T patent/TR199900437T2/en unknown
- 1997-08-29 CZ CZ0058799A patent/CZ297248B6/en not_active IP Right Cessation
- 1997-08-29 ES ES03023272T patent/ES2325206T3/en not_active Expired - Lifetime
- 1997-08-29 AU AU41710/97A patent/AU731162B2/en not_active Expired
- 1997-08-29 HU HU0002980A patent/HUP0002980A3/en unknown
- 1997-08-29 WO PCT/US1997/015258 patent/WO1998008469A2/en active IP Right Grant
- 1997-08-29 ES ES01126359T patent/ES2211722T3/en not_active Expired - Lifetime
- 1997-08-29 EP EP01126359A patent/EP1181908B1/en not_active Revoked
- 1997-08-29 KR KR1020027011281A patent/KR20030097603A/en not_active Application Discontinuation
- 1997-08-29 CA CA002264138A patent/CA2264138C/en not_active Expired - Lifetime
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