Tunable Composite Biomaterials for Enhanced Neuromuscular Regeneration of Volumetric Muscle Loss Injuries
Abstract
While the battle mortality rate for U.S. forces has dropped from 30% in World War II to less than 10% in Afghanistan and Iraq, there has been a parallel increase in the number of seriously injured soldiers who survive with extraordinary injuries, especially complex and severe extremity and head/neck injuries (e.g., polytrauma). To date, there are more than 52,400 wounded in action. As in previous wars, the majority of battlefield injuries involve the extremities. Fifty-three percent of these injuries involve penetrating soft-tissue trauma involving the skin and skeletal muscle, which remains one of the greatest challenges to limb reconstruction. In fact, it could be argued that these statistics dramatically underestimate the magnitude of soft tissue injury, as they are based on primary wounds only. The average wounded Warrior suffers from 2.3 extremity wounds, of which 1.2 involve penetrating soft tissue trauma. When the impact of these wounds on healthcare costs is considered, extremity trauma consumes 65% of the healthcare dollars spent and represents 64% of the disability separations from the military. Examination of military separations due to orthopedic injuries reveals that loss of muscle function due to peripheral nerve injury or direct muscle trauma is second only to amputation as a cause of discharge. In this regard, there are currently no satisfactory therapeutic solutions for full functional restoration of wounded Warriors with significant neuromuscular injuries. As noted above, the complexity of these traumatic neuromuscular injuries and the total number of wounded Warriors affected in recent conflicts warrant development of improved regenerative therapies for more rapid and complete functional recovery. Timely blood vessel formation is well recognized as a major limiting factor for muscle tissue regeneration and repair. The premise of this application is that development of the novel implantable regenerative therapy proposed herein (cells and/or customized biomaterials) will result in improved blood vessel formation beyond that currently achievable, permitting more rapid and complete tissue building. This in turn, will improve neuromuscular regeneration, as well as functional recovery from ever larger volumetric muscle loss (VML) injuries, thus increasing the number of wounded Warriors that could benefit from regenerative therapy. To this end, we propose combining the expertise of accomplished investigators at four prestigious institutions (Walter Reed National Military Medical Center, the Uniformed Services University of the Health Sciences, the University of Virginia, and the University of California, Berkeley) to provide a comprehensive and clinically relevant research strategy. We will use a well-established small animal (rat) model to identify the “best performing” implantable regenerative technology, and then further test the applicability of the best performing technology in a pig VML injury model (the size and nature of the pig VML injury is more relevant to the injuries seen in wounded Warriors). Overall, our combined resources and expertise will provide a unique opportunity for a paradigm shift in the treatment of wounded Warriors with traumatic injuries to the head/neck and extremities. In the end, we hope that our strategy will significantly increase both the quality of life and the rate of return to duty/activity for our wounded Warriors.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810649
Entities
People
- George J. Christ
Organizations
- United States Army
- University of Virginia