Evaluation of Clinically Relevant Regenerative Medicine/Tissue Engineering Therapeutics for Traumatic Extremity Injuries

Laboratory

The Extremity Trauma & Amputation Center of Excellence (EACE) is a one of a kind organization within the Department of Defense consisting of teams of researchers embedded at the point of care within multiple Military Treatment Facilities (MTFs) across the nation. In line with the congressionally directed mission of the EACE, the research efforts undertaken focus on the mitigation, treatment and rehabilitation of traumatic extremity injuries and amputations with a specific focus on translating their findings into clinical practice to improve the care of Servicemembers and Veterans. The proposed preclinical work will be conducted by the EACE-Bethesda team at both Walter Reed National Military Medical Center (WRNMMC), the nation’s largest and most renowned military medical center, and the Uniformed Services University of the Health Sciences (USUHS), the Nation's Federal health sciences university which is committed to excellence in military medicine and public health during peace and war. These world class institutions offer a full suite of infrastructure and facilities which are ideally suited for a wide variety of research activities (i.e., bench to bedside). Importantly, the EACE-Bethesda multidisciplinary team is comprised of basic and translational scientists of varying educational background, and clinicians from across the medical spectrum, which when taken together, provides a privileged perspective of the injury conditions that challenge wounded Servicemembers. Furthermore, due to the aforementioned team, infrastructure, and facilities, subsequent clinical studies can be quickly initiated and conducted, if/when preclinical finding support further translation

Project Description

Traumatic extremity injuries are the hallmark of recent military conflict. The battle mortality rate for US forces has decreased from 30% in WWII to less than 10% in the OIF/OEF conflicts. However, the decreased mortality rate has been accompanied by an increase in the percentage and absolute number of seriously injured soldiers. These soldiers survive but are left with extraordinary, life affecting injuries; especially complex and severe extremity injuries. Indeed, extremity wounds make up the most common survivable injuries of modern military conflict and comprise two-thirds of initial hospital costs to the DoD. 

Volumetric muscle loss (VML), defined as the irrecoverable frank loss of skeletal muscle tissue with associated persistent functional deficits, presents pervasively and is a leading factor in the decision to amputate affected limbs. Given a lack of effective therapeutic treatment options, VML has historically gone without definitive surgical treatment, but rather, the only available standard of care for affected patients is physical therapy. More recently, the field of regenerative medicine has produced several promising technologies for the treatment of VML. Current regenerative paradigms for VML injury have yielded promising pre-clinical results, but require augmentation to achieve a clinically important difference. Looking forward to the requirements for true clinical success in re-establishing function to traumatized limbs with VML injuries, the need to establish comprehensive regenerative and rehabilitative therapies (i.e., Regenerative Rehabilitation) is imminent.

An overarching objective of our research program is to develop individualized, patient-specific (i.e., personalized medicine) Regenerative Rehabilitation based therapies capable of providing the highest level of functional performance and optimal QoL for SMs and veterans with traumatic extremity injuries. However, before this can be achieved, numerous aspects of those injuries, including VML injuries, require further investigation. Thus, pre-clinical Regenerative Rehabilitation themed studies which seek to elucidate these key questions, particularly those focused on VML injuries, are crucial to understanding the fundamental mechanisms related to the interplay between mechanobiology and tissue regeneration.

The primary goal of this study is to develop a synergistic Regenerative Rehabilitation treatment program which facilitates optimal functional outcomes following VML injury. The proposed work will test the hypothesis that optimization of timing of a gold standard rehabilitation therapy will improve the efficacy of a comprehensive regenerative medicine treatment strategy and thus facilitate improved skeletal muscle form and function compared to either the rehabilitation or regenerative interventions in isolation.

This research represents a significant advancement in the understanding of this underrepresented component of care for severe extremity trauma.  If successful, the technology developed through these efforts is primed to transition quickly into clinical practice and has the potential to transform the care and quality of life of Wounded Warriors.

This project will enable the student to:

1. Assist in design, development, execution, and implementation of basic / translational research projects.
2. Gain exposure to various aspects of pre-clinical research, including small animal surgery, necropsy, tissue processing & analysis.
3. Gain experience with contemporary cell & molecular biology analyses and associated data processing & reduction.

Required Skills:

1. Exposure to areas of regenerative medicine, tissue engineering, cellular / molecular immunology, cell biology, or related fields (coursework acceptable)
2. Experience in biomedical wet lab research  (previous lab experience preferable)
3. Experience in technical computing (coursework acceptable)