Conformable tissue repair implant capable of injection delivery

• US 8,496,970 B2
• Filed: 02/27/2012
• Issued: 07/30/2013
• Est. Priority Date: 11/26/2003
• Status: Active Grant

• Current Assignee: Depuy Mitek LLC (Johnson & Johnson)
• Original Assignee: Depuy Mitek LLC (Johnson & Johnson)
• Inventors: Binette, Francois, Hammer, Joseph J., Mukhopadhyay, Krish, Rosenblatt, Joel
• Primary Examiner(s): Marx, Irene
• Assistant Examiner(s): SINGH, SATYENDRA K
• Application Number:
  US13/406,230
• Publication Number:
  US 20120156265A1
• Time in Patent Office: 519 Days
• Field of Search: None
• US Class Current: 424/549
• CPC Class Codes: A61L 27/3604 characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
• CPC Class Codes: A61L 27/3683 subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/3852 Cartilage, e.g. meniscus
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 39/06 Free radical scavengers or antioxidants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents

Abstract

A conformable tissue implant is provided for use in repairing or augmenting a tissue defect or injury site. The tissue implant contains a tissue carrier matrix comprising a plurality of biocompatible, bioresorbable granules and at least one tissue fragment in association with the granules. The tissue fragment contains one or more viable cells that can migrate from the tissue and populate the tissue carrier matrix. Also provided is a method for injectably delivering the tissue implant.

Claims

1. A tissue repair implant, comprising:

a tissue carrier matrix in the form of an injectable suspension, the tissue carrier matrix comprising a plurality of biocompatible, bioresorbable granules and at least one tissue fragment in association with the tissue carrier matrix, the at least one tissue fragment having an effective amount of viable cells that can migrate out of the tissue fragment and populate the tissue carrier matrix;

wherein the at least one tissue fragment has a particle size in the range of about 0.1 to about 2 mm³;

wherein each of the plurality of granules have an average outer diameter in a range of about 150 to about 300 μ

m; and

wherein the at least one tissue fragment is cohesive with the granules within said tissue carrier matrix.

2. The implant of claim 1, wherein the plurality of granules is configured to sieve the at least one tissue fragment from a solution.

3. The implant of claim 1, wherein the at least one tissue fragment has a particle size in the range of about 0.1 to about 2 mm³.

4. The implant of claim 1, wherein the granules comprise at least one of aliphatic polyesters, copoly(ether-esters), solid copolymers of fatty acid esters of glycerol and succinic acid, polyoxaesters, collagen, gelatin, albumin, hyaluronate, glycosaminoglycans, polyanhydrides, polysaccharides, polyphosphazines, subintestinal mucosa, and acellular tissues.

5. The implant of claim 1, wherein the at least one tissue fragment is obtained from a connective tissue type selected from the group consisting of cartilage, meniscus, tendon, ligament, dermis, bone, fat, synovial tissue, muscle tissue, and combinations thereof.

6. The implant of claim 1, wherein the tissue carrier matrix comprises at least one of a proteoglycan, heparan sulfate, heparin, chondroitin sulfate, dermatan sulfate, keratan sulfate, and hyaluronan.

7. The implant of claim 1, wherein the at least one tissue fragment comprises a tissue selected from the group consisting of autogeneic tissue, allogeneic tissue, xenogeneic tissue, and combinations thereof.

8. The implant of claim 1, wherein the granules comprise an aliphatic polyester selected from the group consisting of homopolymers or copolymers of lactides, glycolides, 8-caprolactone, p-dioxanone (1,4-dioxan-2-one), trimethylene carbonate (1,3-dioxan-2-one), and combinations thereof.

9. The implant of claim 1, wherein the tissue carrier matrix further comprises at least one biological component selected from the group consisting of antibiotics, antimicrobial agents, anti-inflammatory agents, growth factors, growth factor fragments, small-molecule wound healing stimulants, hormones, cytokines, proteins, peptides, antibodies, enzymes, isolated cells, glycosaminoglycans, immunosuppressants, nucleic acids, analgesics, platelets, an activator of platelets, viruses, virus particles, and combinations thereof.

10. The implant of claim 1, wherein the at least one biological component is an isolated cell selected from the group consisting of osteocytes, fibroblasts, stem cells, pluripotent cells, chondrocyte progenitors, chondrocytes, osteoclasts, osteoblasts, endothelial cells, macrophages, adipocytes, monocytes, plasma cells, mast cells, umbilical cord cells, leukocytes, stromal cells, mesenchymal stem cells, epithelial cells, myoblasts, tenocytes, ligament fibroblasts, and bone marrow cells.

11. The implant of claim 1, further including a binding agent in association with the tissue carrier matrix.

12. The implant of claim 1, wherein the binding agent is selected from the group consisting of shark cartilage, alginate, hyaluronic acid, collagen gel, fibrin glue, fibrin clot, poly(N-isopropylacrylamide), agarose, chitin, chitosan, cellulose, polysaccharides, poly(oxyalkylene), a copolymer of poly(ethylene oxide)-poly(propylene oxide), poly(vinyl alcohol), polyacrylate, platelet rich plasma (PRP) clot, platelet poor plasma (PPP) clot, Matrigel, blood clot, gelatin-resorcin-formalin adhesives, mussel-based adhesives, dihydroxyphenylalanine (DOPA) based adhesives, transglutaminase, poly(amino acid)-based adhesives, cellulose-based adhesives, polysaccharide-based adhesives, synthetic acrylate-based adhesives, liquid and semi-solid fatty acid esters of glycerol and succinic acid (MGSA), MGSA/polyethylene glycol (MGSA/PEG) copolymers, polyvinylpyrolidone (PVP), PVP copolymers, gelatin, albumin, monoglycerides, diglycerides, triglycerides laminin, elastin, proteoglycans, and combinations thereof.

13. The implant of claim 8, further including a curing agent that crosslinks the binding agent to enable the implant to set.

14. The implant of claim 1, wherein the curing agent is selected from the group consisting of thrombin, calcium, divinyl sulfone (DVS), polyethylene glycol divinyl sulfone (VS-PEG-VS), hydroxyethyl methacrylate divinyl sulfone (HEMA-DIS-HEMA), formaldehyde, glutaraldehyde, aldehydes, isocyanates, alkyl and aryl halides, imidoesters, N-substituted maleimides, acylating compounds, carbodiimide, hydroxychloride, N-hydroxysuccinimide, light, pH, temperature, metal ions, and combinations thereof.

15. The implant of claim 1, wherein the at least one biological component comprises platelets, and further includes an activator of platelets.

16. The implant of claim 1, wherein the activator of platelets is selected from the group consisting of thrombin, calcium, adenosine di-phosphate (ADP), collagen, epinephrine, arachidonic acid, prostaglandin, ristocetin, retinoids, ascorbate, antioxidants, and combinations thereof.

18. The tissue repair implant of claim 16, wherein the binding agent is a fibrin glue.

17. A tissue repair implant, comprising a tissue carrier matrix comprising:

a plurality of biocompatible, bioresorbable granules;

at least one tissue fragment having an effective amount of viable cells that can migrate out of the tissue fragment and populate the tissue carrier matrix; and

a binding agent,

wherein the at least one tissue fragment, granules, and binding agent form a cohesive matrix that is in the form of an injectable suspension; and

wherein each of the plurality of granules have an average outer diameter in a range of about 150 to about 300 μ

m.