Dolph Houben

88 CHAPTER 4 Discussion A future alternative for skeletal reconstruction may be bone vascularized composite allotransplantation (VCA), as living bone allotransplants combine the advantages of cryopreserved allografts with the enhanced healing and remodeling potential of vascularized autogenous bone graft while minimizing the risk of a late stress fracture and resorption [8-10, 28, 29] . However, clinical literature and application of bone VCAs are limited since VCAs rely completely on lifelong immunosuppression with substantial side effects. Experimental bone VCAs have been performed mainly in small animal models testing a variety of strategies to maintain viability without lifelong immunosuppression [11, 12, 20] . The Yucatan miniature swine tibial defect model has been proven to be this valuable and reproducible pre-clinical model to study the application of bone VCAs [23, 30] . Porcine models are also known for their comparable size, anatomy, physiology, and immunology to man [31-34] . The purpose of this study was to evaluate a larger animal VCA model and evaluate the clinical outcome, ambulation and quantify the bone characteristics after tibial VCA. We used both axial compression and cyclic RPI evaluation of allotransplant material properties. Axial compression testing demonstrated allotransplanted bone to have a lower elastic modulus when compared to normal bone at 20 weeks. This is consistent with prior reports of bone VCA [30] [35] . Similar changes were seen with cyclic RPI calculations, consistent with the known changes in mechanical properties reported previously in response to transplantation or transfer [5, 9, 36, 37] . No adverse biomechanical effect of the implementation of an AV-bundle has been observed in both axial compression and cyclic RPI testing. We found nine (9/12) of our tibia defect reconstructions healed at both the proximal and distal junctions 20 weeks after transplantation. Only three cases of incomplete distal union occurred. In clinical settings, secondary bone grafting would have been appropriate to achieve final union in these cases. Early unrestricted ambulation may have contributed to the distal non-union, although none appeared to have signs of painful weight bearing. For example, we have observed pigs “jumping” upon their pen door during feeding only four days after transplantation. We used rigid internal fixation with dual locked LCP-plates knowing that the pigs would immediately begin unrestricted weight bearing. Inability to limit activity in our pig hind-limb models is a potential explanation for the incomplete distal union. In clinical practice, no weight bearing would typically be allowed until radiographic healing has occurred. We observed periosteal new bone arising from the vascularized allotransplant sufficient to form a bridging callous in both groups. This phenomenon is seen in vascularized autografts, but not in cryopreserved allogenic bone. The early development of periosteal callus in both groups is attributable to the patent microvascular anastomoses [24] . Despite the use of only 2 weeks’ immunosuppression, measurable blood flow was maintained for several weeks thereafter through the allogenic nutrient blood supply. The allogenic pedicle eventually lost its patency due to rejection and subsequent thrombosis, six weeks after transplantation. Rejection of the allogenic pedicle is the result of cessation of the immunosuppressive drugs followed by intimal