The Burn/Wound and Regenerative Medicine Laboratory has 3 main focuses:

1.  Heterotopic Ossification: Early diagnsosis and Prevention strategies

As many as 65% of our severely combat-injured service members will go on to develop heterotopic ossification (HO), a musculoskeletal disorder characterized by the formation of mature bone in soft tissues including muscle, tendon, ligaments and fascia. As a complication of trauma, HO presents the most important barrier to functional recovery and independence.Furthermore, over 60% of civilian major burn patients and over 50% of joint replacement surgery patients develop HO, with risks that only increase after subsequent operations.  The pervasive nature of HO extending across several tissue types suggests that treatment directed to a specific tissue may be ineffective, whereas therapy directed towards centrally acting pathways may be more effective.  Once bone forms around a joint, patients develop debilitating joint contractures and loss of mobility. Surgical excision of HO can be attempted to restore function, but patients with periarticular HO rarely regain complete range of motion, with contractures due to persistent or recurring HO.  Current medical strategies to prevent de novo or recurrent HO including glucocorticoids, bisphosphonates, and non-steroidal anti-inflammatory medications either have significant side effects and/or uncertain impact, possibly because they fail to target key pathways involved in HO formation.  In addition to effective therapies, methods of identifying potential HO patients prior to radiographic diagnosis are needed to target early intervention to a population that is likely to benefit.  Given the burden of HO disease in these populations, its high morbidity and suboptimal treatments, there is substantial need for early diagnosis and therapy to inhibit HO by targeting its causative processes.

2.  Bone Tissue Engineering
Alloplastic bone substitutes are prone to infection and inflammation, while autogenous bone grafts are limited in availability and create a donor-site defect. Thus, there is a significant need for readily available autogenous tissue which can aid in bone regeneration without resulting in a donor-site defect. The purpose of this study is to demonstrate the role of ALK2, a BMP type I receptor, as a novel target to 1) improve in vitro mesenchymal stem cell osteogenic differentiation and 2) enhance in vivo bone regeneration and calvarial healing.  

3.  Allograft Survival

Cadaveric allotransplantation offers a promising option for reconstruction in patients with extremity burns and mutilating trauma. However, rejection of transplanted tissues (, hand, or arm) presents a significant clinical barrier to allograft survival. Lymph nodes are a known site of alloantigen presentation, an important step in the development of rejection. The extremities are particularly amenable to interventions involving lymph nodes due to their consistent lymphatic drainage patterns. The goal of the proposed project is to target the sentinel lymph node basin as a method to delay or completely mitigate the immune rejection of an extremity allograft.  We will also characterize additional surgical and therapeutic measures which may further modulate this response.