Enhanced Submucosal Tissue Graft Constructs

Abstract

An improved tissue graft construct comprising submucosa of a warm-blooded vertebrate and a preselected group of eukaryotic cells are described. The improved tissue graft constructs can be used in accordance with the present invention to enhance the repair of damaged or diseased tissues in vivo.

1 . An improved tissue graft construct comprising
 vertebrate submucosa delaminated from both the external smooth muscle layers and the luminal portions of the tunica mucosa and   added primary epithelial cells.   
     
     
         2 . The improved tissue graft construct of  claim 1  wherein the vertebrate submucosa comprises tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa of vertebrate intestinal tissue. 
     
     
         3 . The improved tissue graft construct of  claim 1  wherein the primary epithelial cells are selected from the group consisting of primary gingiva epithelial cells and primary esophageal epithelial cells. 
     
     
         4 . The improved tissue graft construct of  claim 2 , wherein the submucosa is fluidized submucosa. 
     
     
         5 . The improved tissue graft construct of  claim 4 , wherein the fluidized submucosa comprises submucosa digested with an enzyme for a period of time sufficient to solubilize the submucosa. 
     
     
         6 . A composition for the repair of articular cartilage defects, said composition comprising
 tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa of vertebrate intestinal tissue and   added primary chondrocyte cells.   
     
     
         7 . The composition of  claim 6 , wherein the submucosal tissue is fluidized submucosal tissue. 
     
     
         8 . The composition of  claim 7 , wherein the fluidized submucosal tissue comprises submucosal tissue digested with an enzyme for a period of time sufficient to solubilize the tissue. 
     
     
         9 . A method for enhancing the capabilities of a vertebrate submucosa graft construct to repair articular cartilage defects, said method comprising the step of seeding the vertebrate submucosa graft construct with chondrocytes prior to implanting or injecting the vertebrate submucosa graft construct into a host. 
     
     
         10 . The method of  claim 9  further comprising the step of subjecting the seeded vertebrate submucosa graft construct to conditions conducive to the proliferation of the cells prior to implanting or injecting the vertebrate submucosa graft material into the host. 
     
     
         11 . The method of  claim 10  wherein the vertebrate submucosa comprises tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa of vertebrate intestinal tissue. 
     
     
         12 . A method for enhancing the capabilities of a vertebrate submucosa graft construct to repair periodontal defects, said method comprising the step of seeding the vertebrate submucosa graft construct with primary gingiva epithelial cells prior to implanting or injecting the vertebrate submucosa graft construct into a host. 
     
     
         13 . The method of  claim 12  further comprising the step of subjecting the seeded vertebrate submucosa graft construct to conditions conducive to the proliferation of the cells prior to implanting or injecting the vertebrate submucosa graft material into the host. 
     
     
         14 . The method of  claim 12  wherein the vertebrate submucosa comprises tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa of vertebrate intestinal tissue. 
     
     
         15 . An improved tissue graft construct comprising
 vertebrate submucosa delaminated from both the external smooth muscle layers and the luminal portions of the tunica mucosa and   added primary cells.   
     
     
         16 . The improved tissue graft construct of  claim 15  wherein the vertebrate submucosa comprises tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa of vertebrate intestinal tissue. 
     
     
         17 . The improved tissue graft construct of  claim 15  wherein the primary cells are selected from the group consisting of endothelial cells, keratinocytes, chondrocytes, epithelial cells and mesenchymal cells. 
     
     
         18 . The improved tissue graft construct of  claim 16  wherein the submucosa is fluidized submucosa. 
     
     
         19 . The improved tissue graft construct of  claim 18  wherein the fluidized submucosa comprises submucosa digested with an enzyme for a period of time sufficient to solubilize the submucosa. 
     
     
         20 . An improved tissue graft construct comprising
 tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa of vertebrate intestinal tissue, and   a population of cells selected from the group consisting of endothelial cells, keratinocytes and mesenchymal cells.   
     
     
         21 . The improved tissue graft construct of  claim 20  wherein the preselected cell type comprises cells that have been genetically modified. 
     
     
         22 . The improved tissue graft construct of  claim 20  wherein the submucosa tissue is fluidized submucosal tissue. 
     
     
         23 . The improved tissue graft construct of  claim 21  wherein the fluidized submucosal tissue comprises submucosal tissue digested with an enzyme for a period of time sufficient to solubilize the tissue. 
     
     
         24 . A method for enhancing the capabilities of a submucosa graft construct to repair epithelial defects, said method comprising the step of seeding the submucosa with primary epithelial cells prior to implanting or injecting the graft construct into a host. 
     
     
         25 . The method of  claim 24  further comprising the step of subjecting the seeded graft construct to conditions conducive to the proliferation of the cells prior to injecting the graft material into the host. 
     
     
         26 . The method of  claim 24  wherein the submucosa comprises tunica submucosa delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa of vertebrate intestinal tissue.