Tissue-Engineered Skeletal Muscle to Restore Muscle Function Following Soft Tissue Injury
Abstract
Rationale: Injuries to the musculoskeletal system, whether during training or combat, are the leading cause of disability hospitalization in the US Armed Forces; musculoskeletal injuries comprise over 50% of all Department of Defense disabilities and are over three 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 healthcare 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 for the 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 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 lost or 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 specific objectives of this project will be to fabricate larger SMU constructs using methodologies for tissue scale-up pioneered in our lab. We will start by scaling up to a size useful for smaller muscles in the human lower limb. We will fabricate these scaled-up SMUs using both sheep and human cells. We will fully characterize the structure and function, safety, and biocompatibility of SMUs fabricated from human cell sources. We will test the efficacy of the sheep SMUs in a large animal model by implanting the constructs in a model of VML in the hindlimb of a sheep. Applicability of Research: This proposal is in response to the Program Announcement for the Joint Program Committee 8/Clinical and Rehabilitative Medicine Research Program, Extremity Regeneration Technology/Therapeutic Development Award, Funding Opportunity Number: W81XWH-15-DMRDPCRMRP-ERTTDA for Department of Defense, Defense Health Program, Congressionally Directed Medical Research Programs, Defense Medical Research and Development Program. Specifically, we are responding to the request for innovative technologies that may better enable a definitive care solution restore muscle function for military personnel with soft tissue injuries sustained during combat or combat-related activities by proposing to develop a novel tissue engineering technology that will restore muscle volume and function following muscle injury. Our tissue engineered SMU is expected to improve restorative treatments and rehabilitativ
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610752
Entities
People
- Lisa Larkin
Organizations
- United States Army
- University of Michigan