Dolph Houben

135 Viability and immune response to VCA 7 Introduction Vascularized composite allotransplantation (VCA) is used clinically for reconstruction of complex musculoskeletal tissue loss. The ability to replace ‘like with like’ offers a potential improvement over conventional methods in some complex reconstructive situations. All VCA procedures currently require life-long immune modulation to maintain viability to prevent acute and chronic rejection. This approach unfortunately may cause organ toxicity, induction of neoplasms and opportunistic infection among other adverse effects as well as considerable effort and expense to monitor and treating rejection over a lifetime. Bone-only VCA for reconstruction of large bone defects has similar potential and limitations, generally for less life-critical indications [1, 2] . The few reported instances of bone and joint allotransplantation have relied upon drug immunosuppression for tissue survival [3-5] . At present, this requires multi-drug immunosuppression [6, 7] . Efforts to induce donor-specific tolerance have not been proven possible [2, 8] . Alternatively, bone only VCA viability may be preserved by developing a neoangiogenic autogenous blood supply. This effectively switches the circulation that, once developed, will maintain viability without immunosuppression beyond a short initial period. This novel method has proven its potential in multiple studies in rat and rabbit VCA experiments [9-15] . We have demonstrated extensive angiogenesis from implanted AV bundles or facial flaps, improved bone blood flow, active bone remodeling and healing as well as bone material properties equivalent to free vascularized bone autografts. We have demonstrated that bone survival is not due to donor- specific tolerance nor immune deficiency. Transplant survival is facilitated by transplant chimerism, due to repopulation by recipient-derived osteocytes from the new autogenous circulation [16-18] . Recently, we have developed a large porcine tibial orthotopic transplant model to demonstrate similar angiogenesis, healing and limb function as pre-clinical verification [19, 20] . The well-studied pig immunology further permitted this current study of systemic and local immune responses to autogenous angiogenesis within VCA bone segments.