Co-crosslinked hyaluronic acid-silk fibroin hydrogels for improving tissue graft viability and for soft tissue augmentation

Abstract

Hydrogels comprising a macromolecular matrix and water may be used to augment soft tissue of a human being, promote or support cell or tissue viability or proliferation, create space in tissue, and for other purposes. A macromolecular matrix may comprise a hyaluronic acid component crosslinked to a silk fibroin component.

What is claimed is: 
     
         1 . A method of grafting fat in a soft tissue of a human subject, the method comprising:
 (i) injecting a hydrogel component into the soft tissue of the subject, wherein the hydrogel component comprises water and a crosslinked macromolecular matrix, the crosslinked macromolecular matrix comprising a hyaluronic acid component and a silk fibroin component, wherein the hyaluronic acid component is crosslinked to the silk fibroin component by a multiamine cross linker; and   (ii) administering a fat component to the soft tissue of the subject, wherein the fat component contains a lipoaspirate; thereby increasing the volume of fat in the soft tissue of the human subject.   
     
     
         2 . The method of  claim 1 , wherein the injection of the hydrogel component and the administration of the fat component to the soft tissue is performed sequentially. 
     
     
         3 . The method of  claim 2 , wherein the injection of the hydrogel component to the soft tissue precedes the administration of the fat component to the soft tissue. 
     
     
         4 . The method of  claim 2 , wherein the fat component is injected into the soft tissue. 
     
     
         5 . The method of  claim 1 , wherein the multiamine cross linker comprises a diamine cross linker. 
     
     
         6 . The method of  claim 5 , wherein the multiamine cross linker is selected from the group consisting of a hexamethylene diamine (HMDA), lysine, lysine methyl ester, and lysine ethyl ester. 
     
     
         7 . The method of  claim 6 , wherein the multiamine cross linker is lysine methyl ester. 
     
     
         8 . The method of  claim 1 , wherein the silk fibroin is a  B. mori  silk fibroin. 
     
     
         9 . The method of  claim 1 , wherein the crosslinked macromolecular matrix has a weight ratio of the hyaluronic acid to the silk fibroin in the range of about 25:1 to about 1:1. 
     
     
         10 . The method of  claim 1 , wherein the hyaluronic acid component is present in the hydrogel component in a concentration of about 20 mg/mL to about 40 mg/mL, and wherein the silk fibroin component is present in the hydrogel component in a concentration of about 0.1 mg/mL to about 20 mg/mL. 
     
     
         11 . The method of  claim 10 , wherein the hyaluronic acid component is present in the hydrogel component in a concentration of about 9 mg/mL to about 32 mg/mL, and wherein the silk fibroin component is present in the hydrogel component in a concentration of about 1 mg/mL to about 8 mg/mL. 
     
     
         12 . The method of  claim 10 , wherein the hyaluronic acid component is present in the hydrogel component in a concentration of about 16 mg/mL to about 20 mg/mL, and wherein the silk fibroin component is present in the hydrogel component in a concentration of about 2 mg/mL to about 5 mg/mL. 
     
     
         13 . The method of  claim 1 , wherein the hyaluronic acid component has a molecular weight of about 1,000,000 daltons to about 5,000,000 daltons. 
     
     
         14 . The method of  claim 1 , wherein the hyaluronic acid component has a molecular weight of about 1,000,000 daltons to about 3,000,000 daltons. 
     
     
         15 . The method of  claim 1 , wherein fat graft volume retention is increased as compared to administering the fat component alone.