Ischemia-reperfusion injury in vascularized composite allotransplantation

Vascularized composite allotransplantation may now be considered a viable treatment option in patients with complex craniofacial and limb defects. However, the field is still in its infancy, and challenges continue to exist. These challenges, most notably the adverse effects of lifelong immunosuppression, must be weighed against the benefits of the procedure. Improvements in this risk-benefit ratio can be achieved by achieving tolerance and preventing rejection. Five decades after Dr. Joseph E. Murray introduced the field of transplantation to the world, we now have a better understanding of the immunologic factors that may contribute to rejection and inhibit tolerance. In this article, we review emerging evidence that suggests that "danger signals" associated with ischemia-reperfusion injury contribute to innate immune activation, promoting rejection, and inhibiting tolerance. Based on this understanding, we also describe several strategies that may ameliorate the damaging effects of ischemia-reperfusion and the clinical implications of ischemia-reperfusion on the vascularized composite tissue allotransplantation outcome.