Audrey Epstein Reny, Shailesh Agarwal, Ali Salim
Associate Surgeon, Division of Plastic and Reconstructive Surgery, Brigham and Women’s Hospital
Ulrich von Andrian, PhD
Department of Immunology, Harvard Medical School
Indranil Sinha, MD
Department of Surgery, Brigham and Women’s Hospital
Using Biologic Agents to Regenerate Muscles After Traumatic Injury
Traumatic heterotopic ossification (HO)—the pathologic formation of bone in soft tissue—is a significant clinical barrier to patient recovery after musculoskeletal injury due to pain, reduced joint mobility, and open wounds. Patients who have had blunt trauma from motor vehicle accidents, blast injuries, and even those who have had routine orthopaedic procedures are at risk for HO. Using a clinically-representative mouse model, I have shown that a novel recombinant protein, BMPR1A-Fc, significantly reduces traumatic HO. However, two significant challenges to therapeutic use of this biologic agent are: (1) complex and expensive manufacturing processes; and (2) the need for repeated injections over a long duration of time present an impediment to patient adherence.
With funds from the Stepping Strong Innovator Award, Agarwal’s team will develop in vivo adipose tissue bioreactors which synthesize and release BMPR1A-Fc into the injury site. These bioreactors will be composed of a patient’s own adipose (fat) tissue harvested using traditional liposuction techniques. This adipose tissue will then be programmed using novel gene-editing techniques to convert the patient’s adipose tissue into a bioreactor, which expresses our agent of interest, BMPR1A-Fc. This programmed bioreactor can then be injected into the patient as an autologous in vivo bioreactor. The proposed series of studies will initially be performed in our highly representative mouse model of traumatic HO. In the future, however, we envision a platform technology which harnesses a patient’s own cellular machinery to produce and deliver biologic drugs to improve healing after musculoskeletal injury.
Shailesh Agarwal, MD, received his undergraduate degree from the University of Michigan and received his medical degree from the University of Chicago Pritzker School of Medicine. He then completed his residency training in plastic surgery and an NIH-funded post-doctoral research fellowship studying heterotopic ossification and the inflammatory response to trauma at the University of Michigan. He subsequently completed a fellowship in microsurgical reconstruction at the University of Chicago. Agarwal’s clinical interests include reconstruction of the breast, lymphatic system, chest wall, trunk/lower extremity, and head/neck, as well as gender surgery. His laboratory research is centered on genetic and epigenetic re-programming to modify cell function for tissue regeneration.