DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Regenerative Rehabilitation: Towards the Optimization of Rehabilitation Strategies to Improve the Efficacy of Regenerative Therapies for Treatment of VML Injury

Principal Investigator: DEARTH, CHRISTOPHER L
Institution Receiving Award: HENRY M. JACKSON FOUNDATION
Program: DMRDP
Proposal Number: BA180115
Award Number: W81XWH-19-2-0039
Funding Mechanism: Medical Research Award
Partnering Awards:
Award Amount: $296,316.87
Period of Performance: 9/1/2019 - 8/31/2022


PUBLIC ABSTRACT

Volumetric muscle loss (VML) is a type of combat injury that results in massive loss of skeletal muscle. VML among Service members (SMs) evacuated from the battlefield in recent conflicts remains a significant medical problem for the Military Health System (MHS) and Department of Veterans Affairs (VA). While VML injuries do not typically present the most critical (i.e., life or death) medical concern in SMs with multiple traumas early after injury, as time progresses the harmful impact of VML becomes increasingly clear. Specifically, that VML significantly impairs limb movement, reduces quality of life, and promotes disability. Moreover, the functional impairments associated with VML can accelerate other degenerative medical conditions, such as osteoarthritis and low back pain. Therefore, it is of extreme interest to develop treatments for this type of injury that can regrow the essential components of the injured muscles in the body such that strength and dexterity are sufficiently restored to enable return to duty of the Wounded Warrior and ultimately a greater quality of life during and after their service.

There is no widely accepted, currently available technology that orthopedic surgeons can use in the acute reconstruction of VML injuries that will facilitate full restoration of the lost tissue form and function. In some cases, such as VML in the context of open fracture, a muscle or fasciocutaneous flap may be used repair the VML injury. The intent of the flap in this scenario, however, is to improve fracture healing and not muscle regeneration or functional recovery. Beyond the acute/surgical setting, the treatment pathway for VML injury is to provide general physical therapy. While rehabilitation can mediate healing of milder muscle injuries; unfortunately, available clinical data indicate that little functional recovery is observed when a (non-optimized) physical therapy treatment paradigm alone is used to treat VML. What is more, SMs with VML presented progressively worsening disability status despite performing ongoing physical therapy.

Regenerative medicine therapies designed to promote muscle tissue regeneration are under development for the repair of VML injury and are showing encouraging preclinical findings. The field as a whole has demonstrated relative feasibility in implanting a “regenerative” implant and observing a moderate improvement in muscle strength. However, careful observation of the existing data indicate that the level of muscle tissue regeneration is not yet optimized to realize true clinical benefit in extremity VML injuries.

These observations encourage continued innovation to allow these promising therapies, rehabilitative and regenerative, to have beneficial clinical impact, perhaps through synergist effects.

The proposed Regenerative Rehabilitation based study seeks to optimize a physical therapy protocol (i.e., frequency, duration, and time delay to start rehabilitative treatment after the injury) such that the ability of a regenerative therapy to create more functional skeletal muscle tissue is increased. We hypothesize that rehabilitative exercises will promote improvements in the regrowth of the injured muscle such that overall strength, dexterity, and mobility are improved by providing beneficial cues to the cells within the muscle in the form of forces and stretches.

As such, this research represents a significant advancement in the understanding of this underrepresented component of care for severe extremity trauma. If successful, the knowledge developed through these efforts is primed to transition quickly into clinical practice and may prove to be pivotal to achievement of clinically meaningful regenerative and functional outcomes for Wounded Warriors.