Claims for Patent: 9,387,094

Summary for Patent: 9,387,094

Title:	Osteoimplant and method of making same
Abstract:	An osteoimplant is provided which comprises a coherent aggregate of elongate bone particles, the osteoimplant possessing predetermined dimensions and shape. The osteoimplant is highly absorbent and sponge-like in nature. Also provided herein are a method of fabricating the osteoimplant and a method of repairing and/or treating bone defects utilizing the osteoimplant.
Inventor(s):	Manrique; Albert (Manalapan, NJ), Edwards; Jean T. (Hillsborough, NJ), Scarborough; Nelson L. (Andover, MA), Boden; Scott D. (Atlanta, GA), Traianedes; Kathy (North Brunswick, NJ), Shimp; Lawrence A. (Morganville, NJ), Russell; James L. (Little Silver, NJ)
Assignee:	Warsaw Orthopedic, Inc. (Warsaw, IN)
Application Number:	10/137,862
Patent Claims:	1. An osteoimplant which comprises elongate bone particles selected from the group consisting of fully mineralized elongate bone particles, fully demineralized elongate bone particles, substantially fully mineralized elongate bone particles, partially demineralized elongate bone particles, superficially demineralized elongate bone particles, and mixtures thereof wherein mutually contacting elongate bone particles are entangled with each other; wherein the entangled bone particles form a coherent aggregate matrix, wherein the coherent aggregate matrix possesses an open pore, flexible, sponge-like structure configured to absorb fluids while generally retaining predetermined dimensions; and wherein the osteoimplant comprises a core composed of the fully demineralized elongate bone particles which have not been compacted and an outer surface composed of the superficially demineralized elongate bone particles which have not been compacted surrounding the core. 2. The osteoimplant of claim 1, wherein the osteoimplant comprises a continuous three-dimensional structure possessing visible pores. 3. The osteoimplant of claim 1, wherein the osteoimplant comprises about 10-20 grams of the elongated bone particles and the elongated bone particles occupy a volume of about 100-120 cm.sup.3. 4. The osteoimplant of claim 1, wherein the osteoimplant is configured to retain its shape once wetted. 5. The osteoimplant of claim 1, wherein the elongate bone particles represent at least about 50 weight percent of the aggregate. 6. The osteoimplant of claim 1, wherein the elongate bone particles represent at least about 60 weight percent of the aggregate. 7. The osteoimplant of claim 1, wherein the elongate bone particles represent at least about 90 weight percent of the aggregate. 8. The osteoimplant of claim 1, wherein the aggregate further comprises non-elongate bone particles. 9. The osteoimplant of claim 1, wherein the elongate bone particles are obtained from cortical, cancellous, corticocancellous allogenic, xenogenic or transgenic bone tissue. 10. The osteoimplant of claim 1, wherein a median length of the elongate bone particles is from about 2 mm to about 200 mm, a median width of the elongate bone particles is from about 0.05 mm to about 50 mm and a ratio of median length to median width is from about 10:1 to about 2000:1. 11. The osteoimplant of claim 1, wherein a median length of the elongate bone particles is from about 1 mm to about 100 mm, a median width of the elongate particles is from about 0.1 mm to about 20 mm and a ratio of median length to median width is from about 20:1 to about 600:1. 12. The osteoimplant of claim 1, wherein the osteoimplant is swellable upon contact with body and/or irrigation fluids. 13. The osteoimplant of claim 1, wherein the osteoimplant has bulk density of not greater than about 0.3 g/cm.sup.3. 14. An osteoimplant which comprises elongate bone particles selected from the group consisting of substantially fully mineralized elongate bone particles, partially demineralized elongate bone particles, superficially demineralized elongate bone particles, and mixtures thereof, wherein mutually contacting elongate bone particles are entangled with each other; wherein the entangled bone particles form a coherent aggregate matrix, wherein the coherent aggregate matrix possesses an open pore, flexible, sponge-like structure configured to absorb fluids while generally retaining predetermined dimensions; and wherein the osteoimplant comprises a core composed of the superficially demineralized elongate bone particles which have not been compacted and an outer surface composed of the partially demineralized elongate bone particles which have not been compacted surrounding the core, wherein the non-compacted superficially demineralized elongate bone particles that make up the core of the osteoimplant contain a higher percentage of their original mineral content than do the non-compacted partially demineralized elongate bone particles that make up the outer surface of the osteoimplant. 15. An osteoimplant which comprises a carrier, a wetting agent and a coherent aggregate matrix of elongate bone particles having a median length of from about 0.05 mm to about 200 mm and a ratio of median length to median width of from about 10:1 to about 2000:1, the osteoimplant having the elongate bone particles distributed throughout, the elongate bone particles selected from the group consisting of substantially fully mineralized elongate bone particles, partially demineralized elongate bone particles, superficially demineralized elongate bone particles, fully demineralized elongate bone particles, and mixtures thereof, wherein mutually contacting elongate bone particles are entangled with each other; wherein the aggregate matrix possess an open pore, flexible, sponge-like structure and is configured to absorb fluids while generally retaining a predetermined dimension; wherein the wetting agent comprises a liquid polyhydroxy compound; and wherein the osteoimplant comprises a core composed of the superficially demineralized elongate bone particles which have not been compacted and an outer surface composed of the fully demineralized elongate bone particles which have not been compacted surrounding the core. 16. The osteoimplant of claim 15 wherein the elongate bone particles are admixed with one or more components selected from the group consisting of binders/fillers, plasticizers, biostatic/biocidal agents, bioactive substances, surface active agents prior to, during and/or after forming the aggregate into the osteoimplant. 17. The osteoimplant of claim 16 wherein the elongate bone particles are admixed with a binder/filler, and wherein the binder/filler is selected from the group consisting of cyanoacrylates, epoxy-based compounds, dental resin sealants, dental resin cements, calcium phosphate and calcium sulfate self-setting cements, glass ionosin cements, calcium phosphate and calcium sulfate self-setting cements, glass ionomer cements, polymethyl methacrylate, gelatin-resorcinol-formaldehyde glues, protein and collagen-based glues, acrylic resins, cellulosics, bioabsorbable polymers selected from the group consisting of polyglycolide, polylactide, glycolide-lactide copolymers, polycaprolactone, polyanhydrides, polycarbonates, polyorthoesters, polyamino acids, polyarylates, polycyanoacrylates, polyhydroxybutyrate, polyhydroxyvalyrate, polyphosphazenes, polyvinylpyrrolidone, polyarylates, tyrosine-based polycarbonets and polyarylates, carbohydrate polymers, polyiminocarbonates, polypropylene fumarates, polyanhydride esters, polytetrafluroethylene hexacryl, Hyaluronic acid, fibrin, fibrin-collagen, polyethylene glycol glues, mucopolysaccharides and mussell adhesive proteins, fatty acids and fatty acid derivatives. 18. The osteoimplant of claim 16 wherein the elongate bone particles are admixed with a binder/filler, and wherein the binder/filler is selected from the group consisting of bone powder, demineralized bone powder, porous calcium phosphate ceramics, hydroxyapatite, tricalcium phosphate, Bioglass.RTM. and other calcium phosphate materials, calcium sulfate or calcium carbonate particles. 19. The osteoimplant of claim 16 wherein the elongate bone particles are admixed with a biostatic/biocidal agent, and wherein the biostatic/biocidal agent is selected from the group consisting of antibiotics, povidone, sugars and mucopolysaccharides. 20. The osteoimplant of claim 16 wherein the elongate bone particles are admixed with a surface-active agent, and wherein the surface-active agent is selected from the group consisting of biocompatible nonionic, cationic, anionic and amphoteric surfactant. 21. The osteoimplant of claim 16 wherein the elongate bone particles are admixed with a bioactive substance, and wherein the bioactive substance is selected from the group consisting of trophic factors, analgesics, anti-cancer agents, vaccines, adjuvants, antibodies, neuroleptics, genes and genetic elements for transfection, cells or cellular components, collagen, insoluble collagen derivatives, and soluble solids and/or liquids dissolved therein, antiviricides, particularly those effective against HIV and hepatitis; antimicrobials and/or antibiotics selected from the group consisting of erythromycin, bacitracin, neomycin, penicillin, polymicin B, tetracyclines, biomycin, chloromycetin, and streptomycins, cephalosporins, ampicillin, azactam, tobramycin, clindamycin and gentamicin; biocidal/biostatic sugars selected from the group consisting of dextran, and glucose; amino acids, peptides, vitamins, inorganic elements, co-factors for protein synthesis; hormones; endocrine tissue or tissue fragments, synthesizers; enzymes selected from the group consisting of collagenase, peptidases, oxidases, polymer cell scaffolds with parenchymal cells, angiogenic drugs and polymeric carriers containing such drugs; collagen lattices; antigenic agents; cytoskeletal agents; cartilage fragments, modified living cells selected from the group consisting of chondrocytes, bone marrow cells, mesenchymal stem cells, natural extracts, genetically engineered living cells or otherwise modified living cells, DNA delivered by plasmid or viral vectors, genes or genetic elements, tissue transplants, demineralized bone powder, autogenous tissues, blood, serum, soft tissue, bone marrow, bioadhesives; non-collagenous proteins, osteopontin, osteonectin, bone sialo protein, laminin, fibrinogen, vitronectin, thrombospondin, proteoglycans, decorin, beta glycan, biglycan, aggrecan, versican, tenascin, matrix gla protein, hyaluronan, amino acids, amino acid residues, peptides, bone morphogenic proteins (BMPs); osteoinductive factor (OIF); fibronectin (FN); endothelial cell growth factor (ECGF); cementum attachment extracts (CAE); ketanserin; human growth hormone (HGH); animal growth hormones; epidermal growth factor (EGF); interleukin-1 (IL-1); human alpha thrombin; transforming growth factor (TGF-beta); insulin-like growth factor (IGF-1) (IGF-2); platelet derived growth factors (PDGF); fibroblast growth factors (FGF, aFGF, bFGF, etc.); periodontal ligament chemotactic factor (PDLGF); somatotropin; bone digestors; antitumor agents; immuno-suppressants; fatty acids (including polar and non-polar fatty acids); permeation enhancers, fatty acid esters, laureate, myristate and stearate monoesters of polyethylene glycol, enamine derivatives, alpha-keto-aldehydes, and nucleic acids; inorganic elements, inorganic compounds, cofactors for protein synthesis, hormones, soluble and insoluble components of the immune system; soluble and insoluble receptors including truncated forms; soluble, insoluble and cell surface bound ligands including truncated forms; chemokines, bioactive compounds that are endocytosed; endocrine tissue or tissue fragments, growth factor binding proteins, insulin-like growth factor binding protein (IGFBP-2) (IGFBP-4) (IGFBP-5) (IGFBP-6); angiogenic agents, bone promoters, cytokines, interleukins, genetic material, genes encoding bone promoting actions, cells containing genes encoding bone promoting action; growth hormones selected from the group consisting of somatotrophin; bone digestors; antitumor agents; cellular attractants and attachment agents; immunosuppressants; bone resorption inhibitors and stimulators; angiogenic and mitogenic factors; bioactive factors that inhibit and stimulate secondary messenger molecules; cell adhesion molecules, cell-matrix and cell-cell adhesion molecules; secondary messengers, monoclonal antibodies specific to cell surface determinants on mesenchymal stem cells, clotting factors; externally expanded autograft or xenograft cells, nucleic acids and any combination thereof. 22. The osteoimplant of claim 15 wherein the liquid polyhydroxy compound is glycerol. 23. The osteoimplant of claim 15 wherein the elongate bone particles are in a lyophilized state. 24. The osteoimplant of claim 15 wherein the elongate bone particles are cross-linked. 25. The osteoimplant of claim 15, wherein the osteoimplant is swellable upon contact with body and/or irrigation fluids. 26. The osteoimplant of claim 15, the osteoimplant having a shape selected from the group consisting of a sheet, plate, disk, cone, pin, screw, tube, tooth, tooth root, plug, bone or portion of bone, wedge or portion of wedge, cylinder or threaded cylinder. 27. The osteoimplant of claim 15, the osteoimplant including at least one recess therein. 28. The osteoimplant of claim 15 wherein the osteoimplant is provided in at least one cavity of an implant for bone repair. 29. The osteoimplant of claim 28 wherein the implant for bone repair is an intervertebral implant. 30. The osteoimplant of claim 28 which the implant for bone repair is a fusion cage. 31. The osteoimplant of claim 11 wherein the elongate bone particles possess a ratio of median length to median width of from about 20:1 to about 600:1. 32. The osteoimplant of claim 15 wherein the osteoimplant is configured for use in posterolateral procedures. 33. The osteoimplant of claim 15, wherein the superficially demineralized elongate bone particles include one or more regions of surface-exposed collagen. 34. The osteoimplant of claim 15, wherein the fully demineralized elongate bone particles contain less than about 8% of their original mineral content. 35. The osteoimplant of claim 15, wherein the mutually contacting elongate bone particles are mechanically entangled. 36. The osteoimplant of claim 15, wherein the mutually contacting elongate bone particles are naturally entangled. 37. The osteoimplant of claim 15, wherein the elongate bone particles have a median length of about 0.05 mm and a ratio of median length to median width of about 10:1. 38. The osteoimplant of claim 15, wherein the coherent aggregate matrix has a bulk density of not greater than about 0.3 g/cm.sup.3. 39. The osteoimplant of claim 15, wherein the coherent aggregate matrix has a bulk density of approximately 0.114 g/cm.sup.3. 40. The osteoimplant of claim 15, wherein the coherent aggregate matrix optionally includes bone particles selected from the group consisting of substantially fully demineralized elongate bone particles, substantially fully demineralized non-elongate bone particles, substantially fully mineralized non-elongate bone particles, partially demineralized non-elongate bone particles, superficially demineralized nonelongate bone particles and mixtures thereof. 41. The osteoimplant of claim 15, wherein the osteoimplant comprises a compression strength of from about 5 to about 200 MPa. 42. The osteoimplant of claim 15, wherein the osteoimplant comprises a compression strength of from about 25 to about 75 MPa. 43. The osteoimplant of claim 15, wherein the osteoimplant includes a concave depression configured to receive graft material. 44. The osteoimplant of claim 43, wherein the depression is a trough. 45. The osteoimplant of claim 44, further comprising sidewalls surrounding the trough. 46. The osteoimplant of claim 43, wherein the depression is performed. 47. The osteoimplant of claim 43, further comprising sidewalls surrounding the concave depression.

Details for Patent 9,387,094

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Smith & Nephew, Inc.	SANTYL	collagenase	Ointment	101995	06/04/1965		2020-07-19