Regenerative Rehabilitation Solutions to Improve Functional Limitations and Plasticity Following Volumetric Muscle Loss
Abstract
Battlefield casualty and trauma often results in major injury to the extremities; one example of this is volumetric muscle loss (VML) injuries. While advances in prolonged field care have saved many Warfighters lives, those with VML injuries are left with long-term functional complications. Unlike more simple muscle injuries, VML injuries are not capable of undergoing significant self-repair. Furthermore, simple muscle injuries have known, validated, and highly reproducible rehabilitation protocols that return those injured to full function, while there are no current evidence-based rehabilitation protocols to improve function following VML injuries. Our central hypothesis is that, to improve function (i.e., strength, power, endurance) following VML injury (1) optimal evidence-based rehabilitation needs to be developed; (2) treatment of physiologic limitations needs to occur in conjunction with rehabilitation; and (3) long-term impacts of both injury and treatment need to be understood across the neuromusculoskeletal system (e.g., bone and muscle) to support the long-term health of those injured. Our overall goals are to optimize regenerative rehabilitation solutions to skeletal muscle and bone pathology following limb trauma that will improve Warfighter performance and quality of life. Research Applicability: Our proposed work directly addresses the DMRDP JCP-8/CRMRP RESTORE Focus Areas of (1) optimization of Warfighter performance following limb trauma or loss and (2) solutions to accelerate recovery and restore Warfighter performance in training and operational environments. By studying and understanding the pathophysiology, we can correct the dysfunction and resistant plasticity to improve function. We have established clinically relevant VML models, rehabilitation paradigms, treatment approaches, and a research program focused on the pathology of the remaining tissue after VML. Our specific objective for this proposal is to combine rehabilitation strategies (e.g., physical activity) with technologies to correct underlying pathophysiology (e.g., fibrosis) in a regenerative rehabilitation paradigm to support functional improvements across both muscle and bone. The mechanical link between muscle and bone allows the two tissues to scale functional and structural capacities with increased or decreased use. Our work suggests that muscle weakness associated with VML injury causes considerable declines in bone function, even when co-morbid fracture is absent. Clinical and Patient Alignment and Timelines: This work will advance the efficacy of regenerative rehabilitation approaches and is expected to impact a range of military Service members from those acutely injured in current and forthcoming conflicts to those that have already transitioned to the VA health care system and are confronting the chronic devastating outcomes of injury on the muscle and bone. We expect that the research outcomes can be used to test these regenerative rehabilitation approaches in large animal models of VML injury, which we have significant expertise in. If successful, we plan to collaborate with our clinical colleagues to test these approaches in the clinic and ultimately inform clinical care guidelines. We expect this proposal will provide a foundation for evidence-based regenerative rehabilitation paradigms that will be transformative to the VML injured patient. This work addresses the most significant extremity injury among Warfighters evacuated from the battlefield. The long-term functional limitations of VML injury extensively impairs long-term health. While the burden of VML injury is directly on the Warfighters, it is likely that an extended burden is also felt by the Warfighters family and team of caregivers. With this, any increase in the functional capacity of those wounded is expected to also decrease the care burden of the Warfighters caregivers.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010885
Entities
People
- Sarah M Greising
Organizations
- United States Army
- University of Minnesota