Enzyme-activated collagen and tissue matrices

Abstract

Devices and methods for treating defects in connective tissue are provided along with methods for making such devices. The devices can include enzyme-activated acellular tissue matrices that facilitate regrowth of the damaged tissue.

What is claimed is: 
     
         1 . A method for preparing a tissue matrix composition comprising:
 selecting a collagen-based tissue matrix; and   contacting the matrix with a composition containing at least one enzyme that can cleave matrikines from the matrix;   wherein the composition containing the enzyme further contains a deactivating agent for reversibly eliminating the activity of the enzyme.   
     
     
         2 . The method of  claim 1 , wherein the tissue matrix comprises an acellular tissue matrix. 
     
     
         3 . The method of  claim 2 , wherein the acellular tissue matrix comprises an acellular dermal matrix. 
     
     
         4 . The method of  claim 2 , wherein the acellular tissue matrix comprises an acellular porcine dermal matrix. 
     
     
         5 . The method of  claim 1 , wherein the composition containing at least one enzyme is a solution containing at least one enzyme. 
     
     
         6 . The method of  claim 1 , wherein the substrate for the enzyme is a tissue matrix protein. 
     
     
         7 . The method of  claim 1 , wherein the enzyme is matrix metalloproteinase (MMP). 
     
     
         8 . The method of  claim 7 , wherein the MMP is selected from MMP-1, MMP-3, or MMP-9. 
     
     
         9 . The method of  claim 1 , wherein the composition comprises an additional enzyme. 
     
     
         10 . The method of  claim 9 , wherein the additional enzyme comprises an MMP, an elastase, or a dispase. 
     
     
         11 . The method of  claim 1 , wherein the deactivating agent is a chelating agent. 
     
     
         12 . The method of  claim 11 , wherein the chelating agent comprises EDTA, EGTA, or orthophenanthroline. 
     
     
         13 . The method of  claim 1 , further comprising exposing the tissue matrix to a disinfectant. 
     
     
         14 . The method of  claim 13 , wherein the disinfectant is isopropyl alcohol. 
     
     
         15 . The method of  claim 1 , further comprising sterilizing the tissue matrix. 
     
     
         16 . The method of  claim 15 , wherein sterilizing the matrix comprises application of ethylene oxide, propylene oxide, gamma irradiation, or e-beam irradiation. 
     
     
         17 . The method of  claim 1 , further comprising lyophilizing the tissue matrix. 
     
     
         18 . The method of  claim 1 , further comprising storing the tissue matrix in a hydrated state. 
     
     
         19 . The method of  claim 1 , further comprising adding a bioactive substance to the tissue matrix. 
     
     
         20 . The method of  claim 19 , wherein the bioactive substance comprises an antibacterial agent, a cytokine, a growth factor, non-collagenous tissue, or cells.