Neurotization to Improve Graft Reinnervation and Recovery Following Severe Muscle Injuries
Abstract
The objective of the proposed research is to use a surgical technique that regains muscle function in muscle grafts implanted in severe muscle defects. The rationale for this research is that implanted grafts do not contribute to force production or help muscle regain function because they are not innervated. Our hypothesis is that introducing nerve cells into the muscle graft at the time the graft is implanted will improve overall muscle function. Instead of waiting for peripheral nerve to grow or seeding grafts with nerve cells, we will directly neurotize the graft using an intact nerve. This is termed neurotization. Neurotization is a surgical strategy that implants a peripheral nerve stump into the muscle belly. This method harnesses the body’s natural ability to sprout new axons from a nerve stump and puts new nerve cells in close proximity to muscle fibers that need to be innervated and regain function. Yet, nerve implantations such as neurotization are rarely considered in severe muscle defects. Speculation as to why limited research has been performed following muscle injury has not been clarified, but one possible reason could be that most clinicians believe the graft will become fibrotic regardless of the surgical strategy chosen. Our muscle allograft has been shown to promote muscle regeneration with new, centrally located nuclei in the center of our allograft following 8 weeks implantation. We also demonstrated that muscle allografts reduced the degree of fibrosis that occurs compared to the clinical standard, autologous muscle grafts. These data suggest that muscle allografts behave differently than other products commonly used in severe muscle defects. Interestingly, while muscle allograft mediated muscle regeneration, the new muscle fibers appeared to be denervated. Thus, neurotization is a natural build to determine if neural surgical strategies will improve muscle force outcomes. Further, we are encouraged by data in neurotization studies that demonstrate muscle recovery in chronically denervated muscle. If successful, neurotization strategies can easily be implemented into the clinic. These neurorehabilitation techniques can be used in patients with injuries that involve crush, laceration, blast, and tumor resection with minimal risk. These types of patients can be citizens or Veterans who have had months of denervation after muscle injury, they can be combat members who were more recently affected in battle, or they can be citizens or Veterans involved in motor vehicle accidents or construction accidents. Using neurotization on these patients would save the United States and the military millions or billions of dollars every year considering we already spend $400 billion each year on surgery and rehabilitation for these types of patients. We plan to determine the success rate of neurotization studies using our muscle allografts and compare those to the clinical standard, autologous grafts over the course of 3 years. If successful, we will then move to larger animal studies and even Phase I clinical trials using neurotization alongside muscle flap and free muscle flap surgeries. Those secondary studies could make an impact as soon as 2-3 years following this 3-year animal study. Active and inactive military members will benefit from this research. Advancements in body armor have improved Soldier survival rates while exposing the extremities to levels of violence that would have previously been considered fatal. Trauma contributes to the global burden of disease and injury in upwards of $400 billion yearly in associated medical costs and loss of productivity in the United States have been reported. It was also reported that over 33% of all admissions to Polytraumatic Rehabilitation Centers were the result of blast injuries that severely damaged extremity muscles. Our proposal uses a material that is capable of regenerating new, functional muscle and allows us to develop studie
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810352
Entities
People
- Michael J McClure
Organizations
- United States Army
- Virginia Commonwealth University