Dolph Houben

97 Neoangiogenensis, transplant viability and molecular analysis of bone VCA 5 Introduction Current treatment options for large bone defects are associated with significant problems and complications. Vascularized bone autografts provide a good treatment option since they contain an intrinsic blood flow and remain viable over time. When compared to another common reconstructive method using cryopreserved allograft bone, their viability enables better healing, less risk of stress fracture, and a unique ability to remodel or even hypertrophy in response to loading. Vascularized bone autografts such as iliac crest and fibula are available for large defects although size and shape match with most segmental defects is poor. Stability and healing is improved when combined with a cryopreserved matched allograft segment [6] , but either method requires flap harvest and resultant donor site morbidity [7-9] . Transplantation of living allogenic bone, a form of vascularized composite allotransplantation (VCA) would potentially combine the benefits of living bone and the ability to closely match the specific defect morphology without donor site complications. It has seldom been performed clinically, in part because allotransplant viability requires lifelong drug immunosuppression (IS). Its risks include organ toxicity, opportunistic infection and risk of neoplasm, ethically problematic to replace a non-life-critical structure. Previous studies have demonstrated that bone VCAs may be maintained in small animal models without the need of long-term IS by switching the circulation of the transplant from allogenic to autogenous vessels, enabled by implantation of an arteriovenous bundle (AV-bundle) elevated from adjacent soft tissue and placed within the allotransplant. The allogenic nutrient vessels are repaired microsurgically at the same time, but only short-term immunosuppression is used [1, 2, 4, 10-12] . The immunosuppressive period allows the nutrient pedicle to maintain transplant blood flow and cell viability. During this short period, angiogenesis from the AV-bundle develops to provide long-term bone perfusion. Because the anatomy and physiology of small animals differ from patients, we cannot necessarily extrapolate these data to humans. Our porcine tibial defect model more closely approximates clinical use, due to similarities with human physiology as well as transplanted bone size and shape [4, 13] . This study reports transplant viability, formation of neoangiogenic circulation, bone remodeling and biologic activity after transplantation in a series of bone VCAs using this methodology avoiding the need of long-term IS.