Comprehensive Approach to Regeneration of Injured Skeletal Muscles via Sustained Delivery of Growth Factors and Progenitor Cells
Abstract: Complete regeneration of skeletal muscles following trauma or disease often presents a significant challenge. Here, we show that sustained and localized delivery of regenerative growth factors (VEGF/IGF) or progenitor myoblasts via alginate hydrogels ameliorates loss of skeletal muscle vascularization, restores muscle fibers morphology and sustains innervation after injury by promoting both maintenance and re-growth of damaged axons. Further, we explore novel signaling mechanisms of VEGF-mediated regenerative actions using both in vitro and in vivo modeling systems, and describe novel signaling paradigms in regenerating adult skeletal muscle tissue governing interactions between neural and vascular networks. Specifically, these studies produce evidence of novel mechanisms of VEGF actions, further broaden the understanding of angiogenesis and axonal regeneration in skeletal muscles, and suggest therapeutic approaches to improve axonal and ischemic tissue repair in target organs.