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.

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