Neurotization to Improve Graft Reinnervation and Recovery Following Severe Muscle Injuries

Extremity soft tissue trauma can result in permanent loss of skeletal muscle mass and denervation, posing a significant clinical challenge in the military. Clinical options are to either neglect the wound, expecting fibrosis to develop, or to perform surgery and fill the muscle void with a local autologous muscle graft. The development of non-contractile tissue (mainly fibrosis) in the muscle injury is typically observed in cases where neural innervation is irrecoverable and muscle function is severely impaired. Interruption of the intramuscular neural connections in these devastating injuries is a serious regenerative obstacle that is rarely considered. We demonstrate here that muscle force is recovered only slightly through the use of DMM and autograft, confirming what typically occurs functionally in VML injuries. When we investigated histological data we indeed showed that our findings support the hypothesis that severing those intramuscular neural connections potentially impairs muscle regeneration. In this project, we determined that DMM and autograft are sufficient to support some new muscle fiber growth and satellite cell activity. Furthermore, we demonstrated positive AChR-gamma and NCAM staining in DMM treated sites and autograft treated sites. In addition, DMM sites had more intense staining for AChRs compared to autograft. Collectively, these data suggest that these intramuscular neural connections are important in maintaining contractile properties of muscle fibers and could potentially regulate muscle regeneration. Future studies will demonstrate whether improving innervation within the existing muscle or in the graft area will improve muscle regeneration.