Enhancement of skeletal muscle stem cell engraftment by dual delivery of vegf and igf-1

Abstract

An improved device and method for extended repair and regeneration of muscle tissue. An exemplary device comprises (a) a scaffold comprising an ECM component; (b) a combination of growth factors such as VEGF and IGF; and (c) a population of myogenic cells. Implantation of the device leads to muscle regeneration and repair over an extended period of time.

1 . A hydrogel comprising a combination of vascular endothelial growth factor 165 (VEGF 165 ) and insulin-like growth factor-1 (IGF-1). 
     
     
         2 . The hydrogel of  claim 1 , further comprising a population of myogenic cells. 
     
     
         3 . (canceled) 
     
     
         4 . The hydrogel of  claim 1 , wherein said hydrogel comprises macropores. 
     
     
         5 . (canceled) 
     
     
         6 . The hydrogel of  claim 1 , wherein said hydrogel is lyophilized and compressed prior to administration to a subject. 
     
     
         7 . The hydrogel of  claim 6 , wherein said hydrogel comprises shape-memory. 
     
     
         8 .- 10 . (canceled) 
     
     
         11 . The hydrogel of  claim 1 , wherein said hydrogel comprises an open, interconnected porous structure. 
     
     
         12 . The hydrogel of  claim 1 , wherein said hydrogel comprises macropores of about 5-500 microns in diameter. 
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . A method of enhancing reinnervation of muscle tissue, comprising introducing into a muscle tissue of a human subject a device comprising the hydrogel of  claim 1 , wherein the VEGF 165  and IGF-1 are released from the device into the muscle tissue, and wherein introduction of the device into the muscle tissue provides a synergistic effect on muscle reinnervation in the human subject. 
     
     
         16 . The method of  claim 15 , wherein said muscle tissue comprises skeletal muscle tissue. 
     
     
         17 . The method of  claim 15 , wherein said muscle tissue comprises smooth muscle tissue. 
     
     
         18 . The method of  claim 15 , wherein said muscle tissue comprises cardiac tissue. 
     
     
         19 . The method of  claim 15 , wherein the device is introduced into a muscle tissue of the human subject using a needle or an angiocatheter. 
     
     
         20 . The method of  claim 15 , wherein the muscle reinnervation occurs at the neuromuscular junction. 
     
     
         21 . The method of  claim 15 , wherein the muscle tissue is ischemic. 
     
     
         22 . The hydrogel of  claim 1 , wherein the hydrogel comprises alginate. 
     
     
         23 . The hydrogel of  claim 22 , wherein the alginate comprises low molecular weight alginate and high molecular weight alginate. 
     
     
         24 . The method of  claim 15 , wherein the muscle tissue is a limb tissue. 
     
     
         25 . The method of  claim 15 , wherein the subject suffers from ischemia. 
     
     
         26 . The method of  claim 15 , wherein the subject suffers from a muscle injury. 
     
     
         27 . The method of  claim 15 , wherein the VEGF 165  is released from the device in a sustained manner over time, and wherein the IGF-1 is released from the device at a faster rate than the VEGF 165 . 
     
     
         28 . The method of  claim 15 , wherein the device is injectable. 
     
     
         29 . The method of  claim 15 , wherein the device is implantable.