Clinical Translation of Advanced Technologies for Muscle and Nerve Regeneration
Abstract
Rationale: Injuries to the musculoskeletal system, whether during training or combat, are the leading cause of disability hospitalization in the U.S. Armed Forces. Musculoskeletal injuries comprise over 50% of all Department of Defense disabilities and are over 3 times more prevalent than the next-leading cause of disability in the Armed Forces. In the civilian population, end-stage organ failure or tissue loss is one of the most devastating and costly problems in medicine. It is estimated that over 8 million surgical procedures are performed each year, incurring a health care cost of more than $400 billion annually. Organ and tissue replacement is limited by availability and immuno-rejection. One such musculoskeletal injury that exceeds the body’s ability to self-repair muscle and where novel technologies are needed is volumetric muscle loss or VML. VML is defined as the injury to a muscle that is so large that the body cannot repair the injury and results in a loss of function to the injured muscle. VML can be the result of muscle trauma, post-operative damage, or disease. To date, the treatments for VML are not very effective and, as with all organ replacement therapies, are hindered by limited tissue availability and donor site morbidity. An engineered functional skeletal muscle tissue that has functional neural interfaces and when implanted allows full recovery of native muscle forces could be used for repair or replacement of diseased or damaged muscle and will have immediate and long-term effects on patient care and restoration of function for those who have sustained combat-related VML injuries. To address the clinical need for large volumes of readily implantable skeletal muscle tissue, our laboratory has developed a tissue-engineered functional skeletal muscle unit (SMU) of appropriate size and function for clinical use in situations of small VML injuries, such as those found in the hand and face. When used for tissue repair in small animal models, the SMU develops a capillary system, grows new muscle cells, and produces the force required to support bodily functions. Our engineered muscle tissue could be used to restore the function of a complex tissue, e.g., muscle, following traumatic VML sustained in combat. Restoring damaged muscle will allow for restoration of facial expression, ambulation, or daily tasks required for long-term quality of life for our Warfighters and for the general public. Objective: The long-term goal of our laboratory is to engineer a tissue-engineered functional SMU that has functional neuromuscular, myotendinous, and enthesis interfaces and, when implanted, allows rapid and complete recovery of native muscle forces. Thus, the goal of the previously funded proposal (Award Number: W81XWH-16-1-0752) was to develop an engineered skeletal muscle that was large enough to replace large volumes of muscles damaged in traumatic injury or surgery and apply our tissue engineering technology as an “off-the-shelf” tissue replacement to Warfighters or civilians within hours of the initial injury, as well as to utilize the tissues in a regenerative medicine context months and years after the initial tissue loss. While the data from this awarded project were promising, we identified several aspects of the current technology that need further investigation to improve the product and the clinical outcomes of the SMU technology. This new proposal will investigate improvements to the current technology. Applicability of Research: This proposal is in response to the Program Announcement for the Armed Forces Institute of Regenerative Medicine (AFIRM) III, Funding Opportunity Number: W81XWH-19-DMRDP-RMFRA. The Clinical and Rehabilitative Medicine Research Program (CRMRP) focuses on the innovations required to reset our wounded Service members, both in terms of duty performance and quality of life. Specifically, the Fiscal Year 2019 Joint Program Committee 8/CRMRP Regenerative Medicine Foc
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010839
Entities
People
- George J. Christ
Organizations
- United States Army
- University of Virginia