Tissue engineering scaffolds promoting martix protein production

Abstract

The present invention provides methods for repair or replacement of tissue comprising applying or implanting, at a site in need of repair, a tissue engineering scaffold. The present invention also provides tissue engineering scaffolds capable of inducing extracellular matrix production by a cell attached to the tissue engineering scaffold comprising: a scaffold; a polymer tether covalently coupled to the scaffold; and a matrix-enhancing molecule that is covalently coupled to the polymer tether, wherein the matrix-enhancing molecule is present at a concentration sufficient to elicit production of extracellular matrix by the cell attached to the tissue engineering scaffold without increasing cellular proliferation of the attached cell, wherein the matrix-enhancing molecule is selected from the group consisting of ascorbic acid, angiotensin II, insulin-like growth factor, and combinations thereof.

1 . A method for repair or replacement of tissue comprising applying or implanting, at a site in need of repair, a tissue engineering scaffold, wherein the tissue engineering scaffold comprises: 
 a scaffold;    a polymer tether covalently coupled to the scaffold; and    a matrix-enhancing molecule that is covalently coupled to the polymer tether, wherein the matrix-enhancing molecule is present at a concentration sufficient to elicit production of extracellular matrix by a cell attached to the tissue engineering scaffold without increasing cellular proliferation of the attached cell, wherein the matrix-enhancing molecule is selected from the group consisting of ascorbic acid, angiotensin II, insulin-like growth factor, and combinations thereof.    
     
     
         2 . The method of  claim 1  wherein the tissue engineering scaffold further comprises a cell attached to the tissue engineering scaffold.  
     
     
         3 . The method of  claim 2  wherein the cell is attached to the tissue engineering scaffold by constraining the cell within the scaffold.  
     
     
         4 . The method of  claim 3  wherein the scaffold is a hydrogel.  
     
     
         5 . The method of  claim 2  wherein the cell is selected from the group consisting of smooth muscle cells, endothelial cells, fibroblasts, chondrocytes, and combinations thereof.  
     
     
         6 . The method of  claim 1  wherein the matrix-enhancing molecule is ascorbic acid.  
     
     
         7 . The method of  claim 1  wherein the matrix-enhancing molecule is angiotensin II.  
     
     
         8 . The method of  claim 1  wherein the matrix-enhancing molecule is insulin-like growth factor.  
     
     
         9 . The method of  claim 1  wherein the scaffold is formed from a biocompatible polymer selected from the group consisting of a synthetic polymer, a natural polymer, an inorganic material, and combinations thereof.  
     
     
         10 . The method of  claim 1  wherein the scaffold is formed from a biocompatible, biodegradable polymer.  
     
     
         11 . The method of  claim 1  wherein the scaffold is formed from a biocompatible polymer that is not biodegradable.  
     
     
         12 . The method of  claim 1  wherein the scaffold is formed from a biocompatible polymer that is a hydrogel.  
     
     
         13 . The method of  claim 1  wherein the scaffold is formed from a biocompatible polymer that is a polyethylene glycol-diacrylate polymer hydrogel.  
     
     
         14 . The method of  claim 1  wherein the scaffold is formed from a biocompatible polymer that is an alginate hydrogel.  
     
     
         15 . The method of  claim 1  wherein the scaffold is formed from a biocompatible polymer that is a malleable, ionic hydrogel.  
     
     
         16 . The method of  claim 1  wherein the polymer tether has a molecular weight of between about 200 and about 10,000.  
     
     
         17 . The method of  claim 1  wherein the tether has a molecular weight of between about 2,000 and about 6,000.  
     
     
         18 . The method of  claim 1  wherein the tissue is selected from the group consisting of vascular tissue, cartilage, tendons, ligaments, and combinations thereof.  
     
     
         19 . A tissue engineering scaffold capable of inducing extracellular matrix production by a cell attached to the tissue engineering scaffold comprising: 
 a scaffold;    a polymer tether covalently coupled to the scaffold; and    a matrix-enhancing molecule that is covalently coupled to the polymer tether, wherein the matrix-enhancing molecule is present at a concentration sufficient to elicit production of extracellular matrix by the cell attached to the tissue engineering scaffold without increasing cellular proliferation of the attached cell, wherein the matrix-enhancing molecule is selected from the group consisting of ascorbic acid, angiotensin II, insulin-like growth factor, and combinations thereof.    
     
     
         20 . The method of  claim 19  wherein the tissue engineering scaffold further comprises a cell attached to the tissue engineering scaffold.  
     
     
         21 . The method of  claim 20  wherein the cell is attached to the tissue engineering scaffold by constraining the cell within the scaffold.  
     
     
         22 . The method of  claim 21  wherein the scaffold is a hydrogel.  
     
     
         23 . The tissue engineering scaffold of  claim 20  wherein the cell is selected from the group consisting of smooth muscle cells, endothelial cells, fibroblasts, chondrocytes, and combinations thereof.  
     
     
         24 . The tissue engineering scaffold of  claim 19  wherein the matrix-enhancing molecule is ascorbic acid.  
     
     
         25 . The tissue engineering scaffold of  claim 19  wherein the matrix-enhancing molecule is angiotensin II.  
     
     
         26 . The tissue engineering scaffold of  claim 19  wherein the matrix-enhancing molecule is insulin-like growth factor.  
     
     
         27 . The tissue engineering scaffold of  claim 19  wherein the polymer tether has a molecular weight of between about 200 and about 10,000.  
     
     
         28 . The tissue engineering scaffold of  claim 19  wherein the tether has a molecular weight of between about 2,000 and about 6,000.  
     
     
         29 . The tissue engineering scaffold of  claim 19  wherein the scaffold is formed from a biocompatible polymer selected from the group consisting of a synthetic polymer, a natural polymer, an inorganic material, and combinations thereof.  
     
     
         30 . The tissue engineering scaffold of  claim 19  wherein the scaffold is formed from a biocompatible polymer that is not biodegradable.  
     
     
         31 . The tissue engineering scaffold of  claim 19  wherein the scaffold is formed from a biocompatible polymer that is a hydrogel.  
     
     
         32 . The tissue engineering scaffold of  claim 19  wherein the scaffold is formed from a biocompatible polymer that is a polyethylene glycol-diacrylate polymer hydrogel.  
     
     
         33 . The tissue engineering scaffold of  claim 19  wherein the scaffold is formed from a biocompatible polymer that is an alginate hydrogel.  
     
     
         34 . The tissue engineering scaffold of  claim 19  wherein the scaffold is formed from a biocompatible polymer that is a malleable, ionic hydrogel.