Graft materials containing bioactive substances, and methods for their manufacture

Abstract

Described are packaged, sterile medical graft products containing controlled levels of a growth factor such as Fibroblast Growth Factor-2 (FGF-2). Also described are methods of manufacturing medical graft products wherein processing, including sterilization, is controlled and monitored to provide medical graft products having modulated, known levels of a extracellular matrix factor, such as a growth factor, e.g. FGF-2. Preferred graft materials are extracellular matrix materials isolated from human or animal donors, particularly submucosa-containing extracellular matrix materials. Further described are ECM compositions that are or are useful for preparing gels, and related methods for preparation and use.

1 - 10 . (canceled) 
     
     
         11 . A medical product, comprising a packaged, sterile extracellular matrix material isolated from animal tissue and comprising components native to said tissue including collagen, growth factors, proteoglycans, and glycosaminoglycans, and having extractable, bioactive Fibroblast Growth Factor-2 (FGF-2) at a level of at least about 50 ng/g dry weight. 
     
     
         12 . The medical product of  claim 11 , wherein the extracellular matrix material comprises submucosa. 
     
     
         13 . The medical product of  claim 12 , wherein the submucosa is small intestinal submucosa. 
     
     
         14 . The medical product of  claim 12 , wherein the submucosa is porcine. 
     
     
         15 . The medical product of  claim 11 , wherein the FGF-2 is present at a level of at least about 60 ng/g dry weight. 
     
     
         16 . The medical product of  claim 11 , wherein the FGF-2 is present at a level of at least about 70 ng/g dry weight. 
     
     
         17 . The medical product of  claim 11 , wherein the FGF-2 is present at a level of at least about 80 ng/g dry weight. 
     
     
         18 . The medical product of  claim 11 , wherein the FGF-2 is present at a level of at least about 100 ng/g dry weight. 
     
     
         19 . The medical product of  claim 11 , wherein the extracellular matrix material has been sterilized with radiation. 
     
     
         20 . The medical product of  claim 19 , wherein the material has been sterilized with e-beam radiation. 
     
     
         21 - 105 . (canceled) 
     
     
         106 . A small intestinal submucosa medical product, comprising:
 a sterile graft construct enclosed in a medical package;   said graft construct including at least one sheet of an extracellular matrix material comprising small intestinal submucosa from a warm-blooded vertebrate animal;   said extracellular matrix material comprising bioactive Fibroblast Growth Factor-2 (FGF-2) from a source tissue for the extracellular matrix material;   said extracellular matrix material comprising bioactive Transforming Growth Factor-beta (TGF-beta) from a source tissue for the extracellular matrix material;   said extracellular matrix material comprising bioactive Vascular Endothelial Growth Factor (VEGF) from a source tissue for the extracellular matrix material; and   said extracellular matrix material comprising glycosamnoglycans, glycoproteins and proteoglycans from a source tissue for the extracellular matrix material;   
     
     
         107 . The medical product of  claim 106 , wherein the extracellular matrix material is from a porcine animal. 
     
     
         108 . The medical product of  claim 106 , wherein the graft construct has been sterilized while enclosed in the medical package by exposure to ethylene oxide gas, e-beam radiation or gas plasma. 
     
     
         109 . The medical product of  claim 108 , wherein the graft construct comprises a multilaminate construct including multiple sheets of an extracellular matrix material comprising small intestinal submucosa from a warm-blooded vertebrate animal. 
     
     
         110 . The medical product of  claim 109 , wherein the graft construct has a three-dimensional form. 
     
     
         111 . The medical product of  claim 110 , wherein the three-dimensional form is a generally tubular form. 
     
     
         112 . A small intestinal submucosa medical product, comprising:
 a sterile graft construct enclosed in a medical package;   said graft construct including at least one sheet of an extracellular matrix material comprising small intestinal submucosa from a warm-blooded vertebrate animal;   said extracellular matrix material comprising bioactive Fibroblast Growth Factor-2 (FGF-2) from a source tissue for the extracellular matrix material;   wherein the graft construct has been sterilized while enclosed in the medical package by exposure to ethylene oxide gas, with said exposure effective to sterilize the graft construct while reducing the level of extractable, bioactive FGF-2 in the extracellular matrix material to less than 40% of a starting level of extractable, bioactive FGF-2 present in the extracellular matrix material at the start of said exposure.   
     
     
         113 . The medical product of  claim 112 , wherein the graft construct comprises a multilaminate construct including multiple sheets of an extracellular matrix material comprising small intestinal submucosa from a warm-blooded vertebrate animal. 
     
     
         114 . The medical product of  claim 112 , wherein the graft construct has a three-dimensional form. 
     
     
         115 . The medical product of  claim 115 , wherein the three-dimensional form is a generally tubular form.