Glue for cartilage repair

• US RE42,208 E1
• Filed: 06/26/2008
• Issued: 03/08/2011
• Est. Priority Date: 04/29/2003
• Status: Active Grant

• Current Assignee: Musculoskeletal Transplant Foundation
• Original Assignee: Musculoskeletal Transplant Foundation
• Inventors: Tomford, William W., Sunwoo, Moon Hae, Truncale, Katherine Gomes, Gertzman, Arthur A.
• Primary Examiner(s): Ford; Allison M
• Application Number:
  US12/147,042
• Time in Patent Office: 985 Days
• Field of Search: None
• US Class Current: 424/93.7
• CPC Class Codes: A61B 17/00491 Surgical glue applicators surgical adhesives A61L24/00; two-component delivery syringes A61M5/19
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61F 2/30744 End caps, e.g. for closing an endoprosthetic cavity
• CPC Class Codes: A61F 2/30756 Cartilage endoprostheses A61F2/3603 takes precedence
• CPC Class Codes: A61F 2/3094 Designing or manufacturing processes
• CPC Class Codes: A61F 2/3859 Femoral components
• CPC Class Codes: A61F 2002/2817 Bone stimulation by chemical reactions or by osteogenic or biological products for enhancing ossification, e.g. by bone morphogenetic or morphogenic proteins [BMP] or by transforming growth factors [TGF]
• CPC Class Codes: A61F 2002/2867 Bone marrow
• CPC Class Codes: A61F 2002/30062 (bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
• CPC Class Codes: A61F 2002/30224 cylindrical
• CPC Class Codes: A61F 2002/30225 Flat cylinders, i.e. discs
• CPC Class Codes: A61F 2002/30759 Mosaicplasty, i.e. using a plurality of individual cartilage plugs for filling a substantial cartilage defect
• CPC Class Codes: A61F 2002/30764 Cartilage harvest sites
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2230/0069 cylindrical
• CPC Class Codes: A61F 2310/00365 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61F 2310/00383 Gelatin
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 35/32 Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
• CPC Class Codes: A61K 38/18 Growth factors; Growth regulators
• CPC Class Codes: A61K 38/28 : Insulins
• CPC Class Codes: A61L 2430/06 : for cartilage reconstruction, e.g. meniscus
• CPC Class Codes: A61L 27/20 : Polysaccharides
• CPC Class Codes: A61L 27/24 : Collagen
• CPC Class Codes: A61L 27/3612 : Cartilage, synovial fluid
• CPC Class Codes: A61L 27/3654 : Cartilage, e.g. meniscus
• 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 27/3817 : Cartilage-forming cells, e.g. pre-chondrocytes
• CPC Class Codes: A61L 27/3821 : Bone-forming cells, e.g. osteoblasts, osteocytes, osteoprogenitor cells
• CPC Class Codes: A61L 27/3834 : Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
• CPC Class Codes: A61L 27/3852 : Cartilage, e.g. meniscus
• CPC Class Codes: A61L 27/48 : with macromolecular fillers
• CPC Class Codes: A61L 27/56 : Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 27/58 : Materials at least partially resorbable by the body

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.

Claims

1. A sterile allograft cartilage defect implant repair material for use in human beings, comprising a mixture including lyophilized, freeze-milled allograft cartilage pieces sized less having a size not greater than 1 mm and a bioabsorbable carrier, said cartilage pieces being formed from allograft cartilage that has been lyophilized so that their as to reduce its water content ranges from to an amount within the range of from about 0.1% to about 8.0% in a bioabsorbable carrier by weight.

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 repair material as claimed in claim 1, wherein said bioabsorbable carrier is selected from the group consisting of sodium hyaluronate and its derivatives hyaluronic acid.

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

6. A sterile allograft cartilage defect implant repair material as claimed in claim 1, wherein said implant material mixture includes the addition of autologous chondrocytes to achieve a concentration exceeding the concentration of chondrocytes naturally occurring in the patient 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 from 20 years to 55 years.

7. A sterile allograft cartilage defect implant repair material as claimed in claim 1, wherein said milled allograft cartilage is pieces include hyaline cartilage.

8. A sterile allograft cartilage defect implant repair material as claimed in claim 1, wherein said milled allograft cartilage is fibrosus cartilage pieces include fibrocartilage.

9. A sterile allograft cartilage defect implant repair material as claimed in claim 1, wherein said milled allograft cartilage is pieces include hyaline and fibrosus cartilage fibrocartilage.

10. A sterile allograft cartilage defect implant repair material as claimed in claim 1, including wherein said mixture includes an additive to said implant material consisting of one or more of a selected from the group consisting of a growth factors factor, human allogenic cells, human allogenic bone marrow cells, human autologous bone marrow cells, human allogenic stem cells, human autologous stem cells, a human demineralized bone matrix, and insulin, insulin-like growth factor-1, an interleukin-1, receptor agonist, a hepatocyte growth factor, a platelet-derived growth factor, Indian hedgehog, and a parathryroid hormone-related peptide.

11. A sterile cartilage defect repair material as claimed in claim 10, wherein said growth factors are one or more of a factor is selected from the group consisting of FGF-2, FGF-5, IGF-1, TGF-β

, BMP-2, BMP-7, PDGF, and VEGF.

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

40. A cartilage defect repair material as claimed in claim 1, wherein said cartilage pieces are present in said mixture at an amount within the range of from about 25% to about 50% by weight, and said bioabsorbable carrier is present in said mixture at an amount within the range of from about 50% to about 75% by weight.

41. A cartilage defect repair material as claimed in claim 1, wherein said cartilage pieces are present in said mixture at an amount within the range of from about 15% to about 30% by weight, and said bioabsorbable carrier is present in said mixture at an amount within the range of from about 70% to about 85% by weight.

42. A cartilage defect repair material as claimed in claim 1, wherein said lyophilized. freeze-milled allograft cartilage pieces lack cell viability.

43. A cartilage defect repair material as claimed in claim 1, wherein said cartilage defect repair material is free of bone pieces.

44. A cartilage defect repair material as claimed in claim 1, wherein said lyophilized, freeze-milled allograft cartilage pieces are formed by a process including the steps of harvesting a donor tissue consisting essentially of articular cartilage, lyophilizing said donor tissue, and freeze-milling said donor tissue.

45. A cartilage defect repair material as claimed in claim 1, wherein said lyophilized, freeze-milled allograft cartilage pieces are formed by milling frozen allograft articular cartilage.

46. A cartilage defect repair material as claimed in claim 1, wherein said lyophilized, freeze-milled cartilage pieces are formed by freezing allograft cartilage with liquid nitrogen and milling the frozen cartilage.

47. A cartilage defect repair material as claimed in claim 1, wherein said cartilage defect repair material is free of added chondrocytes.

48. A cartilage defect repair material as claimed in claim 1, wherein said lyophilized, freeze-milled allograft cartilage pieces have an ability to promote the growth of new articular cartilage in the cartilage defect.

13. A sterile allograft cartilage defect implant repair material for use in human beings, comprising a mixture including lyophilized, freeze-milled allograft articular cartilage pieces ranging from 0.01 mm to 1.0 mm in size in , a bioabsorbable carrier taken selected from a the group consisting of sodium hyaluronate, hyaluronic acid, gelatin, collagen, chitosan, alginate, buffered PBS, Dextran, or and polymers, and allogenic chondrocytes in an amount exceeding the natural occurrence of same in articular cartilage 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 from 20 years and 55 years.

14. A sterile cartilage defect implant repair material as claimed in claim 13, wherein said allograft articular cartilage is pieces include hyaline cartilage.

15. A sterile allograft cartilage defect implant repair material as claimed in claim 13, wherein said milled allograft articular cartilage is fibrous cartilage pieces include fibrocartilage.

16. A sterile allograft cartilage defect implant repair material as claimed in claim 13, wherein said milled allograft articular cartilage is pieces include hyaline cartilage and fibrous cartilage fibrocartilage.

17. A sterile cartilage defect repair material as claimed in claim 13 wherein said implant material includes , further comprising an additive consisting of one or more of a selected from the group consisting of a growth factors factor, 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, insulin-like growth factor-1, interleukin-1 receptor agonist, hepatocyte growth factor, platelet-derived growth factor, Indian hedgehog, and parathyroid hormone-related peptide.

18. A sterile cartilage defect repair material as claimed in claim 17, wherein said growth factors are one or more of a factor is selected from the group consisting of FGF-2, FGF-5, IGF-1, TGF-β

, BMP-2, BMP-7, PDGF, and 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.

49. A cartilage defect repair material as claimed in claim 13, wherein said mixture includes a protein glue.

50. A cartilage defect repair material as claimed in claim 13, wherein said allograft articular cartilage pieces are formed from allograft articular cartilage that has been lyophilized so as to reduce its water content to the range of from about 0.1% to about 8.0% by weight.

51. A cartilage defect repair material as claimed in claim 13, wherein said cartilage pieces are present in said mixture at an amount within the range of from about 25% to about 50% by weight, and said bioabsorbable carrier is present in said mixture at an amount within the range of from about 50% to about 75% by weight.

52. A cartilage defect repair material as claimed in claim 13, wherein said cartilage pieces are present in said mixture at an amount within the range of from about 15% to about 30% by weight, and said bioabsorbable carrier is present in said mixture at an amount within the range of from about 70% to about 85% by weight.

21. A sterile allograft cartilage defect implant repair material for use in human beings, comprising lyophilized, freeze-milled allograft articular cartilage pieces ranging from 0.01 mm to 1.0 mm in size in , a bioabsorbable carrier taken selected from a the group consisting of sodium hyaluronate, hyaluronic acid and its derivatives , gelatin, collagen, chitosan, alginate, buffered PBS, Dextran or , and polymers, and autologous bone marrow cells in an amount exceeding the natural occurrence of same in a patient being treated 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 from 20 years to 55 years.

22. A sterile cartilage defect repair material as claimed in claim 21 including , further comprising an additive in said implant material which consists of one or more of a selected from the group consisting of a growth factors factor, human allogenic cells, autologous chondrocytes, demineralized bone matrix, and insulin, insulin-like growth factor-1, an interleukin-1 receptor agonist, a hepatocyte growth factor, a platelet-derived growth factor, Indian hedgehog, and a parathyroid hormone-related peptide.

23. A sterile cartilage defect repair material as claimed in claim 22, wherein said growth factors are one or more of a factor is selected from the group consisting of FGF-2, FGF-5, IGF-1, TGF-β

, BMP-2, BMP-7, PDGF, and VEGF.

24. A sterile allograft cartilage defect implant repair material as claimed in claim 21, wherein said bioabsorbable carrier consists is selected from the group consisting of sodium hyaluronate, and hyaluronic acid and its derivatives .

25. A sterile cartilage defect repair material as claimed in claim 21;

wherein said lyophilized allograft articular cartilage pieces have ranging from are formed from allograft articular cartilage that has been lyophilized so as to reduce its water content to the range of about 0.1% to about 8.0%.

26. A sterile allograft cartilage defect implant repair material as claimed in claim 21, wherein said allograft articular cartilage is pieces include hyaline cartilage.

27. A sterile allograft cartilage defect implant repair material as claimed in claim 21, wherein said milled allograft articular cartilage is fibrous cartilage pieces include fibrocartilage.

28. A sterile allograft cartilage defect implant repair material as claimed in claim 21, wherein said milled allograft articular cartilage is pieces include hyaline cartilage and fibrous cartilage fibrocartilage.

29. A sterile allograft cartilage defect implant repair material as claimed in claim 21, wherein said milled allograft articular cartilage ranges pieces are present in said material at an amount in the range of from about 25% to about 50% by weight and said bioabsorbable carrier ranges is present in said material at an amount in the range of from about 75% 50% to about 50% 75% by weight.

30. A sterile allograft cartilage defect implant repair material as claimed in claim 21, wherein said milled allograft articular cartilage ranges pieces are present in said material in an amount in the range of from about 15% to about 30% by weight with the and said bioabsorbable carrier ranging is present in said material in an amount in the range of from about 85% 70% to about 70% 85% by weight.

53. A cartilage defect repair material as claimed in claim 21, further comprising a protein glue.

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 repair material in a cartilage defect site in a human being, said the cartilage defect repair material comprising having a mixture including lyophilized freeze-milled allograft articular cartilage which has been lyophilized and mixed in pieces and a bioabsorbable carrier, said method comprising the steps of:

(a) cutting a patient'"'"'s tissue at a site of a cartilage defect to remove a diseased area of cartilage from the cartilage defect site;

(b) adding autologous cells to said the mixture of milled allograft cartilage in a bioabsorbable carrier ;

(c) placing a the mixture of milled allograft cartilage with the added autologous cells in a bioabsorbable carrier in into the cartilage defect area where cartilage has been removed site; and

(d) placing a cover over the mixture of milled allograft cartilage in a bioabsorbable carrier and the added cells so as to contain the mixture and the added cells in the cartilage defect site for a predetermined period of time .

33. The method of claim 32, wherein further comprising the step of adding growth factors are added to said the mixture.

34. The method of claim 32, wherein said autologous cells are include chondrocytes.

35. The method of claim 32, wherein said autologous cells are include bone marrow cells.

36. The method of claim 32, wherein said autologous cells are include stem cells.

54. The method of claim 32, further comprising the step of fixing the mixture in the cartilage defect site with an organic glue.

55. The method of claim 32, 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 cartilage defect site.

56. The method of claim 32, wherein said cover is a periosteal flap.

57. The method of claim 32, wherein said cover is a perichondrial flap.

58. The method of claim 32, wherein, in said step (b), the cells are selected from the group consisting of chondrocytes, bone marrow cells and stem cells, and the cells are added so as to achieve a concentration greater than the concentration of corresponding cells that are naturally present in hyaline cartilage of a human being having an age in the range of from 20 years and 55 years.

37. A sterile allograft cartilage defect implant repair material for use in a human being, comprising a mixture including lyophilized, freeze-milled allograft articular cartilage pieces ranging from 0.01 mm to 1.0 mm in size in , a bioabsorbable carrier taken selected from a the 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 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 from 20 years and 55 years, wherein said milled allograft articular cartilage ranges pieces are present in said mixture at an amount within the range of from about 25% to about 50% by weight and said bioabsorbable carrier ranges is present in said mixture at an amount within the range of from about 75% 50% to about 50% 75% by weight.

38. A sterile allograft cartilage defect implant repair material for use in a human being, comprising a mixture including lyophilized, freeze-milled allograft articular cartilage pieces ranging from 0.01 mm to 1.0 mm in size in , a bioabsorbable carrier taken selected from a the group consisting of gelatin, collagen, and alginate, and autologous chondrocytes in an amount exceeding the natural occurrence of same in articular cartilage 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 from 20 years and 55 years, wherein said milled allograft articular cartilage ranges pieces are present in said mixture at an amount within the range of from about 25% to about 50% by weight and said bioabsorbable carrier ranges is present in said mixture at an amount within the range of from about 75% 50% to about 50% 75% by weight.

39. A sterile allograft cartilage defect implant repair material for use in a human being, comprising a mixture including lyophilized, freeze-milled allograft articular cartilage pieces ranging from 0.01 mm to 1.0 mm in size in , a bioabsorbable carrier taken selected from a the group consisting of buffered PBS, Dextran or , and polymers, and autologous chondrocytes in an amount exceeding the natural occurrence of same in articular cartilage 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 from 20 years and 55 years, wherein said milled allograft articular cartilage ranges pieces are present in said mixture at an amount within the range of from about 25% to about 50% by weight and said bioabsorbable carrier ranges is present in said mixture at an amount within the range of from about 75% 50% to about 50% 75% by weight.

59. A cartilage defect repair material for use in human beings, comprising lyophilized, freeze-milled allograft cartilage pieces having a size not greater than 1 mm, wherein said cartilage pieces are included in a mixture that also includes a bioabsorbable carrier, said cartilage pieces being present in said mixture at an amount within the range of from about 25% to about 50% by weight, and said bioabsorbable carrier being present in said mixture at an amount within the range of from about 50% to about 75% by weight.

60. A cartilage defect repair material as claimed in claim 59, 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 from about 0.1% to about 8.0% by weight.

61. A cartilage defect repair material as claimed in claim 59, wherein said size ranges from 0.01 mm to 1.0 mm.

62. A cartilage defect repair material as claimed in claim 59, wherein said material is free of added chondrocytes.

63. A cartilage defect repair material as claimed in claim 59, wherein said cartilage pieces are formed by freezing allograft cartilage with liquid nitrogen and milling the frozen cartilage.

64. A cartilage defect repair material as claimed in claim 59, wherein said cartilage pieces are formed by freeze-milling allograft cartilage subsequent to lyophilization.

65. A cartilage defect repair material for use in human beings, comprising lyophilized, freeze-milled allograft cartilage pieces having a size not greater than 1 mm, wherein said cartilage pieces are included in a mixture that also includes a bioabsorbable carrier, said cartilage pieces being present in said mixture at an amount within the range of from about 15% to about 30% by weight, and said bioabsorbable carrier being present in said mixture at an amount within the range of from about 70% to about 85% by weight.

66. A cartilage defect repair material as claimed in claim 65, 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 from about 0.1% to about 8.0% by weight.

67. A cartilage defect repair material as claimed in claim 65, wherein said size ranges from 0.01 mm to 1.0 mm.

68. A cartilage defect repair material as claimed in claim 65, wherein said material is free of added chondrocytes.

69. A cartilage defect repair material as claimed in claim 65, wherein said cartilage pieces are formed by freezing allograft cartilage with liquid nitrogen and milling the frozen cartilage.

70. A cartilage defect repair material as claimed in claim 65, wherein said cartilage pieces are formed by freeze-milling allograft cartilage subsequent to lyophilization.

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

72. A method as claimed in claim 71, wherein the cartilage pieces have a water content ranging from about 0.1% to about 8.0% by weight prior to their placement in the defect site.

73. A method as claimed in claim 71, wherein the cartilage pieces are formed from allograft cartilage which has been lyophilized so as to reduce its water content to an amount within the range of from about 0.1% to about 8.0% by weight.

74. A method as claimed in claim 71, wherein the size ranges from 0.01 mm to 1.0 mm.

75. A method as claimed in claim 71, wherein the cartilage pieces are formed by freezing allograft cartilage with liquid nitrogen and milling the frozen cartilage.

76. A method as claimed in claim 71, wherein the cartilage pieces are formed by freeze-milling allograft cartilage subsequent to lyophilization of the allograft cartilage.

77. A method as claimed in claim 71, wherein the defect site includes a defect in articular cartilage.

78. A method as claimed in claim 77, wherein the cartilage pieces have an ability to promote the growth of new articular cartilage in the articular cartilage defect.

79. A method as claimed in claim 71, wherein the lyophilized, freeze-milled allograft cartilage pieces consist essentially of articular cartilage.

80. A method as claimed in claim 71, wherein the lyophilized, freeze-milled allograft cartilage pieces lack cell viability.

81. A method as claimed in claim 71, comprising the further steps of harvesting a donor tissue consisting essentially of articular cartilage, lyophilizing said donor tissue, and freeze-milling said donor tissue.

82. A method as claimed in claim 71, comprising the further step of forming the lyophilized, freeze-milled allograft cartilage pieces by a process including the step of milling frozen allograft articular cartilage.

83. A method as claimed in claim 71, wherein the lyophilized, freeze-milled allograft cartilage pieces are free of added chondrocytes.