Severe craniofacial injuries to US soldiers pose tremendously difficult reconstructive challenges. Twenty-six percent of wounded Soldiers in modern wartime conflicts have sustained maxillofacial injuries ranging from simple facial bone fractures to extensive bone and soft tissue loss. Craniofacial injuries are not only aesthetic challenges, but also present significant functional limitations such as difficulty with speech, oral competence, and facial expression. Reconstructive surgery plays a major role in re-integrating wounded Warriors back to their pre-injury state of function and is critical in their rehabilitation. However, while conventional methods for craniofacial reconstruction are largely successful in achieving wound healing by “filling holes,” they frequently fail in restoring facial function – it does not move; it does not feel like a normal face.

Vascularized composite allotransplantation (VCA) refers to the transplantation of non-organ tissues made up of skin, fat, muscle, bone, nerves, and/or blood vessels from a matched human donor to fulfill a reconstructive role in severely injured soldiers (i.e., craniomaxillofacial transplantation). Unlike conventional craniofacial reconstruction, vascularized composite allografts are comprised of the exact components and functional units that an injured Soldier is missing. Indeed, craniofacial VCA has become a clinical reality, with dozens of successful cases performed in the world. Unfortunately, this technique is markedly limited by the need for lifelong systemic immunosuppression, which carries the risk of organ failure, cancer, and even death. However, with the success of current facial VCA cases (30 worldwide to date), the scientific focus has shifted from the clinical feasibility to optimizing immunosuppression and functional/aesthetic outcomes. Therefore, the development of novel approaches to facilitate minimization of immunosuppression and improve functional/aesthetic outcomes would exponentially expand the clinical use of VCA for reconstruction of a wide range of traumatic and post-ablative injuries.

Based on our preliminary data and the most comprehensive face transplant case to date performed by the Co-Principal Investigator on this proposal, we believe that the inclusion of large pieces of bone from the donor craniofacial skeleton will both permit minimization of immunosuppression as well as markedly improve the way the transplanted face looks and functions. The objectives of this proposal are (1) to develop a directed planning process to design and fabricate personalized surgical devices to perform VCA procedures, (2) conduct a clinical trial of craniofacial VCA using this process and establish outcomes measures, and (3) utilize a novel noninvasive method for immune profiling to minimize immunosuppression and predict acute rejection. We strongly believe that the experiments described in this proposal combined with our unique expertise positions our team for success.

The products of this research will be highly applicable to all the majority of VCA subspecialties, but will also be applicable to areas outside of VCA. The use of personalized devices for craniofacial reconstruction was pioneered by our unit, and the evolution of these devices described in this proposal would be broadly applicable to any type of craniofacial reconstruction (i.e., traumatic, congenital, etc.). Furthermore, this technology is being developed by our unit in extremity and soft tissue reconstruction. The clinical trial of facial VCA will undoubtedly add to our clinical understanding of facial VCA, which will mitigate future risk to permit safer, more efficient procedures and optimize outcomes of future VCA procedures. Finally, the development of an inexpensive noninvasive skin assay for rejection with minimal risk can easily be adaptable to any cutaneous pathology (i.e., skin cancer, radiation injury, psoriasis, burns, trauma, auto-immune disease) for disease surveillance, diagnosis, prognosis, and personalized therapy. These all would have broad application in both the military and civilian markets.