Non-Gelling Soluble Extracellular Matrix with Biological Activity

Abstract

Provided are methods for preparing non-gelling, solubilized extracellular matrix (ECM) materials useful as cell growth substrates. Also provided are compositions prepared according to the methods as well as uses for the compositions. In one embodiment a device, such as a prosthesis, is provided which comprises an inorganic matrix into which the non-gelling, solubilized ECM composition is dispersed to facilitate in-growth of cells into the ECM and thus adaptation and/or attachment of the device to a patient. In another embodiment, the composition is delivered intraarticularly, intrathecally, intraoccularly, intracranially, and into pleural space.

1 - 45 . (canceled) 
     
     
         46 . A composition comprising a solution comprising decellularized, solubilized, terminally sterilized, intact extracellular matrix (ECM) that has not been dialyzed or cross-linked, and an acid protease, the solution having a pH in the range of 7.2 to 7.8, wherein the solution does not form a hydrogel when the temperature of the solution is raised to 37° C. 
     
     
         47 . The composition of  claim 46 , wherein the acid protease is pepsin or trypsin. 
     
     
         48 . The composition of  claim 46 , wherein the ECM is derived from a tissue selected from urinary bladder, spleen, liver, heart, pancreas, ovary, small intestine, large intestine, colon, central nervous system tissue, adipose tissue, bone, esophagus, or dermis. 
     
     
         49 . The composition of  claim 46 , wherein the ECM is derived from small intestinal submucosa (SIS) or urinary bladder matrix (UBM). 
     
     
         50 . The composition of  claim 46 , wherein the pH is in the range of 7.2 to 7.4. 
     
     
         51 . The composition of  claim 46 , wherein the composition is an injectable solution at 37° C. 
     
     
         52 . The composition of  claim 46 , wherein the composition is lyophilized. 
     
     
         53 . The composition of  claim 46 , wherein the composition is contained within, absorbed into, or adsorbed onto a laminar sheath of non-comminuted and non-digested ECM. 
     
     
         54 . The composition of  claim 46 , wherein the composition further comprises a cell. 
     
     
         55 . The composition of  claim 46 , wherein the composition further comprises a chemoattractant, a cytokine, or an antibiotic. 
     
     
         56 . The composition of  claim 46 , wherein the ECM is mammalian ECM. 
     
     
         57 . The composition of  claim 56 , wherein the mammalian ECM is selected from human, monkey, pig, cow, or sheep ECM. 
     
     
         58 . A composition comprising:
 an acidic solution comprising an acid protease and decellularized, solubilized, terminally sterilized, intact extracellular matrix (ECM) that has not been dialyzed or cross-linked, wherein the acidic solution, once neutralized, does not form a hydrogel when the temperature is raised to 37° C.   
     
     
         59 . The composition of  claim 58 , wherein the composition, when neutralized, has a pH of 7.2 to 7.8. 
     
     
         60 . The composition of  claim 58 , wherein the composition, when neutralized, has a pH of 7.2 to 7.4. 
     
     
         61 . The composition of  claim 60 , wherein the acid protease is pepsin or trypsin. 
     
     
         62 . The composition of  claim 58 , wherein the ECM is derived from a tissue selected from urinary bladder, spleen, liver, heart, pancreas, ovary, small intestine, large intestine, colon, central nervous system tissue, adipose tissue, bone, esophagus, or dermis. 
     
     
         63 . The composition of  claim 58 , wherein the ECM is derived from small intestinal submucosa (SIS) or urinary bladder matrix (UBM). 
     
     
         64 . The composition of  claim 58 , wherein the ECM is mammalian ECM. 
     
     
         65 . The composition of  claim 64 , wherein the mammalian ECM is selected from human, monkey, pig, cow, or sheep ECM.