Porated cartilage products

Abstract

This invention provides porated cartilage products, methods of producing porated cartilage products, and methods of treating subjects by administering cartilage products. Optionally, the cartilage products are sized, porated, and digested to provide a flexible cartilage product. Optionally, the cartilage products comprise viable chondrocytes, bioactive factors such as chondrogenic factors, and a collagen type II matrix. Optionally, the cartilage products are non-immunogenic.

What is claimed is: 
     
         1 . A cartilage product comprising partially-digested cartilage, wherein the partially digested cartilage comprises a plurality of pores. 
     
     
         2 . A cartilage product comprising:
 a. a collagen matrix, wherein a substantial amount of the collagen in the collagen matrix is fragmented relative to unmodified articular cartilage;   b. a plurality of pores in the collagen matrix; and   c. viable native cells in the collagen matrix.   
     
     
         3 . The cartilage product of  claim 1 , wherein the cartilage comprises viable native cells. 
     
     
         4 . A cartilage product comprising:
 a. a collagen matrix, wherein a substantial amount of the collagen in the collagen matrix is glycine-terminated collagen fragments; and   b. a plurality of pores in the collagen matrix.   
     
     
         5 . A cartilage product comprising cartilage having about 10 to about 100 pores per cm 2 , wherein:
 a. the diameter of the pores is about 0.2 mm to about 2 mm; and   b. the cartilage has greater flexibility than unmodified articular cartilage.   
     
     
         6 . The cartilage product of  claim 1 , wherein cartilage is partially-digested. 
     
     
         7 . The cartilage product of  claim 5 , wherein cartilage is partially-digested. 
     
     
         8 . The cartilage product of  claim 6 , wherein said partially digested collagen is enzyme digested collagen. 
     
     
         9 . The cartilage product of  claim 8 , wherein said enzyme is a proteinase, optionally wherein said proteinase is collagenase or collagenase II. 
     
     
         10 . The cartilage product of  claim 1 , wherein the diameter of the pores is selected from: about 0.2 mm to about 2 mm, about 0.5 mm to about 1.5 mm, about 0.8 mm to about 1.2 mm, or about 1 mm. 
     
     
         11 . The cartilage product of  claim 1 , wherein the cartilage has a pore density of about 20 to about 60 pores per cm 2 . 
     
     
         12 . The cartilage product of  claim 2 , wherein the viable cells are chondrocytes. 
     
     
         13 . The cartilage product of  claim 12 , wherein the cartilage product comprises a substantial amount of viable chondrocytes. 
     
     
         14 . The cartilage product of  claim 1 , wherein the cartilage comprises hyaline cartilage, optionally, wherein the hyaline cartilage is selected from: articular cartilage, condoyle cartilage, femur condoyle cartilage, and tibial plateau cartilage. 
     
     
         15 . The cartilage product of  claim 1 , wherein the cartilage product is devoid of a subchondral bone layer, optionally wherein the cartilage product is devoid of a calcified cartilage layer. 
     
     
         16 . The cartilage product of  claim 1 , wherein the cartilage has a thickness of less than about 3 mm. 
     
     
         17 . The cartilage product of  claim 16 , wherein the wherein the cartilage has a thickness of about 0.5 mm to about 2 mm or about 1 mm to about 1.5 mm. 
     
     
         18 . The cartilage product of  claim 16 , wherein the pores extend through the majority of said thickness, optionally wherein the pores extend through the entire thickness of the cartilage. 
     
     
         19 . The cartilage product of  claim 1 , wherein the cartilage product is cryopreserved. 
     
     
         20 . The cartilage product of  claim 1 , wherein the cartilage product has been subjected to a freeze/thaw cycle. 
     
     
         21 . The cartilage product of  claim 1 , wherein the cartilage product comprises chondrogenic factors, optionally, wherein the chondrogenic factors comprise one or more of: TGF-β1, TGF-β2, TGF-β3, BMP-2, BMP-7 bFGF, IGF-1. 
     
     
         22 . The cartilage product of  claim 21 , wherein the cartilage product comprises one or more of:
 a. TGF-β1 in an amount of at least about 11 pg/cm 2 , optionally, about 11 to about 628 pg/cm 2 ;   b. TGF-β3 in an amount of at least about 4 pg/cm 2 , optionally, about 4 to about 112 pg/cm 2 ;   c. BMP-7 in an amount of at least about 3 pg/cm 2 , optionally, about 3 to about 23 pg/cm 2 ;   d. bFGF in an amount of at least about 169 pg/cm 2 , optionally, about 169 to about 365 pg/cm 2 ; and   e. IGF-1 in an amount of at least about 111 pg/cm 2 , optionally, about 111 to about 779 pg/cm 2 .   
     
     
         23 . The cartilage product of  claim 21 , wherein, when cultured in growth media, the cartilage product releases one or more of:
 a. TGF-β1 in an amount of at least about 2617 pg/cm 2 , optionally, about 2617 to about 17818 pg/cm 2 ;   b. TGF-β2 in an amount of at least about 133 pg/cm 2 , optionally, about 133 to about 623 pg/cm 2 ;   c. IGF-1 in an amount of at least about 14 pg/cm 2 , optionally, about 14 to about 2842 pg/cm 2 .