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Last Updated: April 25, 2024

Claims for Patent: RE43258


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Summary for Patent: RE43258
Title:Glue for cartilage repair
Abstract: The invention is directed toward a sterile cartilage defect implant material comprising milled lyophilized allograft cartilage pieces ranging from 0.01 mm to 1.0 mm in size in a bioabsorbable carrier taken from a group consisting of sodium hyaluronate, hyaluronic acid and its derivatives, gelatin, collagen, chitosan, alginate, buffered PBS, Dextran or polymers with allogenic chondrocytes or bone marrow cells in an amount exceeding the natural occurrence of same in hyaline cartilage and adding a cell growth additive.
Inventor(s): Truncale; Katherine G. (Hillsborough, NJ), Sunwoo; Moon Hae (Old Tappan, NJ), Gertzman; Arthur A. (Flemington, NJ), Tomford; William W. (Belmont, MA)
Assignee: Musculoskeletal Transplant Foundation (Edison, NJ)
Application Number:12/966,674
Patent Claims:1. A sterile allograft cartilage defect implant material for use in human beings comprising milled allograft cartilage pieces sized less than 1 mm and lyophilized so that their water content ranges from about 0.1% to about 8.0% in a bioabsorbable carrier..].

.[.2. A sterile allograft cartilage defect implant material as claimed in claim 1 wherein said milled cartilage ranges from about 25% to about 50% by weight and said carrier ranges from about 75% to about 50% by weight..].

.[.3. A sterile allograft cartilage defect implant material as claimed in claim 1 wherein said milled cartilage ranges from about 15% to about 30% by weight with the carrier ranging from about 85% to about 70% by weight..].

.[.4. A sterile allograft cartilage defect implant material as claimed in claim 1 wherein said carrier is sodium hyaluronate and its derivatives..].

.[.5. A sterile allograft cartilage defect implant material as claimed in claim 1 wherein said implant material includes a protein glue..].

.[.6. A sterile allograft cartilage defect implant material as claimed in claim 1 wherein said implant material includes the addition of autologous chondrocytes to achieve a concentration exceeding the concentration of chondrocytes naturally occurring in the patient..].

.[.7. A sterile allograft cartilage defect implant material as claimed in claim 1 wherein said milled cartilage is hyaline cartilage..].

.[.8. A sterile allograft cartilage defect implant material as claimed in claim 1 wherein said milled cartilage is fibrosus cartilage..].

.[.9. A sterile allograft cartilage defect implant material as claimed in claim 1 wherein said milled cartilage is hyaline and fibrosus cartilage..].

.[.10. A sterile allograft cartilage defect implant material claimed in claim 1 including an additive to said implant material consisting of one or more of a group consisting of growth factors, human allogenic cells, human allogenic bone marrow cells, human autologous bone marrow cells, human allogenic stem cells, human autologous stem cells, human demineralized bone matrix, and insulin..].

.[.11. A sterile cartilage repair material as claimed in claim 10 wherein said growth factors are one or more of a group consisting of FGF-2, FGF-5, IGF-1, TGF-.beta., BMP-2, BMP-7, PDGF, VEGF..].

.[.12. A sterile allograft cartilage defect implant material as claimed in claim 1 wherein said carrier comprises one or more bioabsorbable carriers taken from a group consisting of sodium hyaluronate, hyaluronic acid and its derivatives, gelatin, collagen, chitosan, alginate, buffered PBS, Dextran or polymers..].

.[.13. A sterile cartilage defect implant material comprising milled allograft articular cartilage pieces ranging from 0.01 mm to 1.0 mm in size in a bioabsorbable carrier taken from a group consisting of sodium hyaluronate, gelatin, collagen, chitosan, alginate, buffered PBS, Dextran or polymers and allogenic chondrocytes in an amount exceeding the natural occurrence of same in articular cartilage..].

.[.14. A sterile cartilage defect implant material as claimed in claim 13 wherein said allograft articular cartilage is hyaline cartilage..].

.[.15. A sterile allograft cartilage defect implant material as claimed in claim 13 wherein said milled cartilage is fibrous cartilage..].

.[.16. A sterile allograft cartilage defect implant material as claimed in claim 13 wherein said milled cartilage is hyaline and fibrous cartilage..].

.[.17. A sterile cartilage repair material as claimed in claim 13 wherein said implant material includes an additive consisting of one or more of a group consisting of growth factors, human allogenic cells, human allogenic bone marrow cells, human autologous bone marrow cells, human allogenic stem cells, human autologous stem cells, demineralized bone matrix, and insulin..].

.[.18. A sterile cartilage repair material as claimed in claim 17 wherein said growth factors are one or more of a group consisting of FGF-2, FGF-5, IGF-1, TGF-.beta., BMP-2, BMP-7, PDGF, VEGF..].

.[.19. A sterile cartilage defect implant material as claimed in claim 13 wherein said milled cartilage ranges from about 25% to about 50% by weight and said carrier ranges from about 75% to about 50% by weight..].

.[.20. A sterile cartilage defect implant material as claimed in claim 13 wherein said milled cartilage ranges from about 15% to about 30% by weight with the carrier ranging from about 85% to about 70% by weight..].

.[.21. A sterile cartilage defect implant material comprising lyophilized milled allograft articular cartilage pieces ranging from 0.01 mm to 1.0 mm in size in a bioabsorbable carrier taken from a group consisting of sodium hyaluronate, hyaluronic acid and its derivatives, gelatin, collagen, chitosan, alginate, buffered PBS, Dextran or polymers and autologous bone marrow cells in an amount exceeding the natural occurrence of same in a patient being treated..].

.[.22. A sterile cartilage defect repair material as claimed in claim 21 including an additive in said implant material which consists of one or more of a group consisting of growth factors, human allogenic cells, autologous chondrocytes, demineralized bone matrix, and insulin..].

.[.23. A sterile cartilage repair material as claimed in claim 22 wherein said growth factors are one or more of a group consisting of FGF-2, FGF-5, IGF-1, TGF-.beta., BMP-2, BMP-7, PDGF, VEGF..].

.[.24. A sterile cartilage defect repair material as claimed in claim 21 wherein said bioabsorbable carrier consists of sodium hyaluronate, hyaluronic acid and its derivatives..].

.[.25. A sterile cartilage defect material as claimed in claim 21 wherein said lyophilized cartilage pieces have a water content ranging from about 0.1% to 8.0%..].

.[.26. A sterile cartilage defect implant material as claimed in claim 21 wherein said allograft articular cartilage is hyaline cartilage..].

.[.27. A sterile allograft cartilage defect implant material as claimed in claim 21 wherein said milled cartilage is fibrous cartilage..].

.[.28. A sterile allograft cartilage defect implant material as claimed in claim 21 wherein said milled cartilage is hyaline and fibrous cartilage..].

.[.29. A sterile cartilage defect implant material as claimed in claim 21 wherein said milled cartilage ranges from about 25% to about 50% by weight and said carrier ranges from about 75% to about 50% by weight..].

.[.30. A sterile cartilage defect implant material as claimed in claim 21 wherein said milled cartilage ranges from about 15% to about 30% by weight with the carrier ranging from about 85% to about 70% by weight..].

.[.31. A sterile cartilage defect implant material comprising lyophilized milled allograft articular cartilage pieces ranging from 0.01 mm to 1.0 mm in size in a bioabsorbable carrier taken from a group consisting of sodium hyaluronate, hyaluronic acid and its derivatives, gelatin, collagen, chitosan, alginate, buffered PBS, Dextran or polymers and autologous stem cells in an amount exceeding the natural occurrence of same in a patient being treated..].

.[.32. A method of placing a cartilage defect material in a cartilage defect, said cartilage defect material comprising milled allograft articular cartilage which has been lyophilized and mixed in a bioabsorbable carrier comprising the steps of: (a) cutting a patient's tissue at a site of a cartilage defect to remove a diseased area of cartilage; (b) adding autologous cells to said mixture of milled allograft cartilage in a bioabsorbable carrier; (c) placing a mixture of milled allograft cartilage with added autologous cells in a bioabsorbable carrier in the cartilage defect area where cartilage has been removed; and (d) placing a cover over the mixture of milled allograft cartilage in a bioabsorbable carrier to contain the mixture in cartilage defect site for a predetermined period of time..].

.[.33. The method of claim 32 wherein growth factors are added to said mixture..].

.[.34. The method of claim 32 wherein said autologous cells are chondrocytes..].

.[.35. The method of claim 32 wherein said autologous cells are bone marrow cells..].

.[.36. The method of claim 32 wherein said autologous cells are stem cells..].

.[.37. A sterile cartilage defect implant material comprising lyophilized milled allograft articular cartilage pieces ranging from 0.01 mm to 1.0 mm in size in a bioabsorbable carrier taken from a group consisting of sodium hyaluronate, hyaluronic acid and its derivatives and chitosan and autologous chondrocytes in an amount exceeding the natural occurrence of same in articular cartilage, wherein said milled cartilage ranges from about 25% to about 50% by weight and said bioabsorbable carrier ranges from about 75% to about 50% by weight..].

.[.38. A sterile cartilage defect implant material comprising lyophilized milled allograft articular cartilage pieces ranging from 0.01 mm to 1.0 mm in size in a bioabsorbable carrier taken from a group consisting of gelatin, collagen and alginate and autologous chondrocytes in an amount exceeding the natural occurrence of same in articular cartilage, wherein said milled cartilage ranges from about 25% to about 50% by weight and said bioabsorbable carrier ranges from about 75% to about 50% by weight..].

.[.39. A sterile cartilage defect implant material comprising lyophilized milled allograft articular cartilage pieces ranging from 0.01 mm to 1.0 mm in size in a bioabsorbable carrier taken from a group consisting of buffered PBS, Dextran or polymers and autologous chondrocytes in an amount exceeding the natural occurrence of same in articular cartilage, wherein said milled cartilage ranges from about 25% to about 50% by weight and said bioabsorbable carrier ranges from about 75% to about 50% by weight..].

.Iadd.40. A cartilage defect repair material for use in human beings, comprising a mixture having a bioabsorbable carrier and freeze-milled allograft cartilage pieces having a size not greater than 1 mm, said mixture being in the form of a gel..Iaddend.

.Iadd.41. A cartilage defect repair material for use in human beings, comprising a mixture having a bioabsorbable carrier and freeze-milled allograft cartilage pieces having a size not greater than 1 mm, said mixture being in the form of a paste, and said cartilage pieces being present in said mixture in an amount within the range of from about 25% to about 50% by weight..Iaddend.

.Iadd.42. A cartilage defect repair material for use in human beings, comprising a mixture having a bioabsorbable carrier and freeze-milled allograft cartilage pieces having a size not greater than 1 mm, said mixture being in the form of one of a paste and a gel, and said cartilage pieces being present in said mixture in an amount within the range of from about 15% to about 50% by weight..Iaddend.

.Iadd.43. A cartilage defect repair material as claimed in any one of claims 40, 41 and 42, wherein said cartilage pieces are formed from allograft cartilage having a reduced water content..Iaddend.

.Iadd.44. A cartilage defect repair material as claimed in any one of claims 40, 41 and 42, wherein said cartilage pieces are formed from allograft cartilage having a reduced water content within the range of about 0.1% to about 8.0% by weight..Iaddend.

.Iadd.45. A cartilage defect repair material as claimed in any one of claims 40, 41 and 42, wherein said cartilage pieces are formed from allograft cartilage that has been lyophilized so as to reduce its water content to an amount within the range of about 0.1% to about 8.0% by weight..Iaddend.

.Iadd.46. A cartilage defect repair material as claimed in any one of claims 40, 41 and 42, wherein said size is in the range of 0.01 mm to 1.0 mm..Iaddend.

.Iadd.47. A cartilage defect repair material as claimed in any one of claims 40, 41 and 42, wherein said allograft cartilage pieces are allograft articular cartilage pieces..Iaddend.

.Iadd.48. A cartilage defect repair material as claimed in any one of claims 40, 41 and 42, wherein said allograft cartilage pieces include hyaline cartilage..Iaddend.

.Iadd.49. A cartilage defect repair material as claimed in any one of claims 40, 41 and 42, wherein said allograft cartilage pieces lack cell viability..Iaddend.

.Iadd.50. A cartilage defect repair material as claimed in any one of claims 40, 41 and 42, wherein said cartilage defect repair material is free of added chondrocytes..Iaddend.

.Iadd.51. A cartilage defect repair material as claimed in any one of claims 40, 41 and 42, wherein said cartilage defect repair material is free of bone pieces..Iaddend.

.Iadd.52. A cartilage defect repair material as claimed in any one of claims 40, 41 and 42, wherein said mixture is formed for implantation directly in a defect site..Iaddend.

.Iadd.53. A cartilage defect repair material as claimed in any one of claims 40, 41 and 42, wherein said allograft cartilage pieces have an ability to promote the growth of new articular cartilage in a cartilage defect..Iaddend.

.Iadd.54. A cartilage defect repair material as claimed in claim 40, wherein said allograft cartilage pieces are present in said mixture in an amount in the range of from about 15% to about 30% by weight and said bioabsorbable carrier is present in said mixture in an amount in the range of from about 70% to about 85% by weight..Iaddend.

.Iadd.55. A cartilage defect repair material as claimed in claim 41, wherein said bioabsorbable carrier is present in said mixture at an amount in the range of from about 50% to about 75% by weight..Iaddend.

.Iadd.56. A cartilage defect repair material as claimed in claim 42, wherein said bioabsorbable carrier is present in said mixture in an amount within the range of from about 50% to about 85% by weight..Iaddend.

.Iadd.57. A cartilage defect repair material as claimed in any one of claims 40, 41 and 42, wherein said cartilage pieces are formed by freezing allograft cartilage with liquid nitrogen and milling the frozen cartilage..Iaddend.

.Iadd.58. A cartilage defect repair material as claimed in any one of claims 40, 41 and 42, wherein said allograft cartilage pieces are formed by milling frozen allograft articular cartilage..Iaddend.

.Iadd.59. A cartilage defect repair material as claimed in any one of claims 40, 41 and 42, wherein said cartilage pieces are formed by freeze-milling allograft cartilage subsequent to reducing the water content of the allograft cartilage..Iaddend.

.Iadd.60. A cartilage defect repair material as claimed in any one of claims 40, 41 and 42, wherein said allograft cartilage pieces are formed by a process including the steps of harvesting a donor tissue consisting essentially of articular cartilage, reducing the water content of said donor tissue, and freeze-milling said donor tissue..Iaddend.

.Iadd.61. A cartilage defect repair material for use in human beings, comprising freeze-milled allograft cartilage pieces having a size not greater than 1 mm, said cartilage pieces being included in a mixture, said mixture including a bioabsorbable carrier, and said allograft cartilage pieces including fibrocartilage..Iaddend.

.Iadd.62. A cartilage defect repair material for use in human beings, comprising freeze-milled allograft cartilage pieces having a size not greater than 1 mm, said cartilage pieces being included in a mixture, said mixture including a bioabsorbable carrier, and said allograft cartilage pieces including hyaline cartilage and fibrocartilage..Iaddend.

.Iadd.63. A cartilage defect repair material for use in human beings, comprising freeze-milled allograft cartilage pieces having a size not greater than 1 mm, said cartilage pieces being included in a mixture, and said mixture including a bioabsorbable carrier and a protein glue..Iaddend.

.Iadd.64. A cartilage defect repair material for use in human beings, comprising freeze-milled allograft cartilage pieces having a size not greater than 1 mm, said cartilage pieces being included in a mixture, and said mixture including a bioabsorbable carrier selected from the group consisting of sodium hyaluronate, hyaluronic acid, gelatin, collagen, chitosan, alginate, buffered PBS, Dextran, and polymers. .Iaddend.

.Iadd.65. A cartilage defect repair material for use in human beings, comprising freeze-milled allograft cartilage pieces having a size not greater than 1 mm, said cartilage pieces being included in a mixture, and said mixture including a bioabsorbable carrier selected from the group consisting of sodium hyaluronate and hyaluronic acid..Iaddend.

.Iadd.66. A cartilage defect repair material for use in human beings, comprising freeze-milled allograft cartilage pieces having a size not greater than 1 mm, said cartilage pieces being included in a mixture, and said mixture including a bioabsorbable carrier and an additive selected from the group consisting of a growth factor, human allogenic cells, human allogenic bone marrow cells, human autologous bone marrow cells, human allogenic stem cells, human autologous stem cells, human demineralized bone matrix, insulin, insulin-like growth factor-1, interleukin-1 receptor agonist, hepatocyte growth factor, platelet-derived growth factor, Indian hedgehog, and parathyroid hormone-related peptide..Iaddend.

.Iadd.67. A cartilage defect repair material as claimed in claim 66, wherein said growth factor is selected from the group consisting of FGF-2, FGF-5, IGF-1, TGF-.beta., BMP-2, BMP-7, PDGF, and VEGF..Iaddend.

.Iadd.68. A cartilage defect repair material for use in human beings, comprising freeze-milled allograft cartilage pieces having a size not greater than 1 mm, said cartilage pieces being included in a mixture, and said mixture including a bioabsorbable carrier and autologous chondrocytes at a concentration greater than the concentration of chondrocytes that are naturally present in hyaline cartilage of a human being having an age in the range of 20 years to 55 years..Iaddend.

.Iadd.69. A cartilage defect repair material for use in human beings, comprising freeze-milled allograft cartilage pieces having a size not greater than 1 mm, said cartilage pieces being included in a mixture, and said mixture including a bioabsorbable carrier and allogenic chondrocytes at a concentration greater than the concentration of chondrocytes that are naturally present in hyaline cartilage of a human being having an age in the range of 20 years to 55 years..Iaddend.

.Iadd.70. A cartilage defect repair material for use in human beings, comprising freeze-milled allograft cartilage pieces having a size not greater than 1 mm, said cartilage pieces being included in a mixture, and said mixture including a bioabsorbable carrier and autologous bone marrow cells at a concentration greater than the concentration of bone marrow cells that are naturally present in hyaline cartilage of a human being having an age in the range of 20 years to 55 years..Iaddend.

.Iadd.71. A cartilage defect repair material for use in human beings, comprising freeze-milled allograft cartilage pieces having a size not greater than 1 mm, said cartilage pieces being included in a mixture, and said mixture including a bioabsorbable carrier and autologous stem cells at a concentration greater than the concentration of stem cells that are naturally present in hyaline cartilage of a human being having an age in the range of 20 years to 55 years..Iaddend.

.Iadd.72. A method of repairing a cartilage defect in a human being, comprising the step of placing in a defect site freeze-milled allograft cartilage pieces having a size not greater than 1 mm..Iaddend.

.Iadd.73. A method as claimed in claim 72, wherein the cartilage pieces have a water content within the range of about 0.1% to about 8.0% by weight prior to their placement in the defect site..Iaddend.

.Iadd.74. A method as claimed in claim 72, wherein the cartilage pieces are formed from allograft cartilage having a reduced water content..Iaddend.

.Iadd.75. A method as claimed in claim 72, wherein the cartilage pieces are formed from allograft cartilage which has been dried so as to reduce its water content to an amount within the range of about 0.1% to about 8.0% by weight..Iaddend.

.Iadd.76. A method as claimed in claim 72, wherein the size of the cartilage pieces ranges from 0.01 mm to 1.0 mm..Iaddend.

.Iadd.77. A method as claimed in claim 72, wherein the cartilage pieces are formed by freezing allograft cartilage with liquid nitrogen and milling the frozen cartilage..Iaddend.

.Iadd.78. A method as claimed in claim 72, wherein the cartilage pieces are formed by freeze-milling allograft cartilage subsequent to reducing the water content of the allograft cartilage..Iaddend.

.Iadd.79. A method as claimed in claim 72, wherein the defect site includes a defect in articular cartilage..Iaddend.

.Iadd.80. A method as claimed in claim 72, wherein the freeze-milled allograft cartilage pieces consist essentially of articular cartilage..Iaddend.

.Iadd.81. A method as claimed in claim 72, wherein the freeze-milled allograft cartilage pieces lack cell viability..Iaddend.

.Iadd.82. A method as claimed in claim 72, comprising the further steps of harvesting a donor tissue consisting essentially of articular cartilage, reducing the water content of said donor tissue, and freeze-milling said donor tissue..Iaddend.

.Iadd.83. A method as claimed in claim 72, comprising the further step of forming the freeze-milled allograft cartilage pieces by a process including the step of milling frozen allograft articular cartilage..Iaddend.

.Iadd.84. A method as claimed in claim 72, wherein the allograft cartilage pieces are free of added chondrocytes..Iaddend.

.Iadd.85. A method as claimed in claim 79, wherein the cartilage pieces have an ability to promote the growth of new articular cartilage in the articular cartilage defect..Iaddend.

.Iadd.86. A method as claimed in claim 72, comprising the further steps of cutting a patient's tissue to remove a diseased area of cartilage from the defect site; and placing a cover over the allograft cartilage pieces so as to contain the allograft cartilage pieces in the defect site..Iaddend.

.Iadd.87. A method as claimed in claim 86, further comprising the step of adding cells to the defect site..Iaddend.

.Iadd.88. A method as claimed in claim 87, wherein the cells are selected from the group consisting of chondrocytes, bone marrow cells and stem cells..Iaddend.

.Iadd.89. A method as claimed in claim 72, wherein the cartilage pieces are included in a mixture, the mixture including a bioabsorbable carrier..Iaddend.

.Iadd.90. A method as claimed in claim 89, wherein said placing step includes the step of placing the mixture in the defect site, said method comprising the further steps of cutting a patient's tissue to remove a diseased area of cartilage from the defect site; and placing a cover over the mixture so as to contain the mixture in the defect site..Iaddend.

.Iadd.91. A method as claimed in claim 90, further comprising the step of adding cells to the defect site..Iaddend.

.Iadd.92. A method as claimed in claim 91, wherein the cells are selected from the group consisting of chondrocytes, bone marrow cells and stem cells..Iaddend.

.Iadd.93. A method as claimed in claim 90, comprising the further step of adding a growth factor to the mixture..Iaddend.

.Iadd.94. A method as claimed in claim 90, further comprising the step of fixing the mixture in the cartilage defect site with an organic glue..Iaddend.

.Iadd.95. A method as claimed in claim 90, further comprising the step of keeping the cover over the mixture for a predetermined period of time that is sufficient to promote cartilage growth at the defect site..Iaddend.

.Iadd.96. A method as claimed in claim 90, wherein the cover is selected from the group consisting of a periosteal flap and a perichondrial flap..Iaddend.

.Iadd.97. A method for making a cartilage defect repair material for use in human beings from allograft cartilage, said method comprising the steps of freeze-milling the allograft cartilage so as to form freeze-milled allograft cartilage pieces having a size not greater than 1 mm; and mixing the freeze-mill cartilage pieces with a bioabsorbable carrier to form a mixture in the form of a gel..Iaddend.

.Iadd.98. A method for making a cartilage defect repair material for use in human beings from allograft cartilage, said method comprising the steps of freeze-milling the allograft cartilage so as to form freeze-milled allograft cartilage pieces having a size not greater than 1 mm; and mixing the freeze-mill cartilage pieces with a bioabsorbable carrier to form a mixture in the form of a paste, the freeze-milled cartilage pieces being present in the mixture in an amount within the range of from about 25% to about 50% by weight..Iaddend.

.Iadd.99. A method for making a cartilage defect repair material for use in human beings from allograft cartilage, said method comprising the steps of freeze-milling the allograft cartilage so as to form freeze-milled allograft cartilage pieces having a size not greater than 1 mm; and mixing the freeze-mill cartilage pieces with a bioabsorbable carrier to form a mixture in the form of one of a paste and a gel, the freeze-milled cartilage pieces being present in the mixture in an amount within the range of from about 15% to about 50% by weight..Iaddend.

.Iadd.100. A method as claimed in any one of claims 97, 98 and 99, comprising the further step of reducing the water content of the allograft cartilage..Iaddend.

.Iadd.101. A method as claimed in claim 100, wherein said reducing step is performed so as to reduce the water content of the allograft cartilage to an amount within the range of about 0.1% to about 8.0% by weight..Iaddend.

.Iadd.102. A method as claimed in claim 100, wherein said reducing step is performed prior to said freeze-milling step..Iaddend.

.Iadd.103. A method as claimed in claim 100, wherein said reducing step includes the step of lyophilizing the allograft cartilage..Iaddend.

.Iadd.104. A method as claimed in any one of claims 97, 98 and 99, wherein said freeze-milling step includes the step of freezing the cartilage and the step of milling the frozen cartilage..Iaddend.

.Iadd.105. A method as claimed in any one of claims 97, 98 and 99, wherein said freeze-milling step is performed by milling the cartilage in a frozen state..Iaddend.

.Iadd.106. A method as claimed in any one of claims 97, 98 and 99, wherein the freeze-milled cartilage pieces have a water content within the range of about 0.1% to about 8.0% by weight..Iaddend.

.Iadd.107. A method as claimed in any one of claims 97, 98 and 99, wherein the size of the freeze-milled cartilage pieces ranges from 0.01 mm to 1.0 mm..Iaddend.

.Iadd.108. A method as claimed in any one of claims 97, 98 and 99, wherein the allograft cartilage includes allograft articular cartilage..Iaddend.

.Iadd.109. A method as claimed in any one of claims 97, 98 and 99, comprising the further step of harvesting the allograft cartilage from a donor tissue consisting essentially of articular cartilage..Iaddend.

.Iadd.110. A method as claimed in any one of claims 97, 41 and 42, wherein the mixture is formed for implantation directly in a defect site..Iaddend.

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