Dolph Houben

177 Summary and general discussion 9 Part III: In the third part of this thesis, we extrapolated our novel method of surgical neo-angiogenesis to a novel large animal model to study orthotopic vascularized whole knee joint allotransplantation. We hypothesized that surgical angiogenesis will preserve viability, permit healing and maintain articular function of whole knee joint allotransplantation with short-term immunosuppression. In Chapter 8 , we performed an anatomy and feasibility study on allotransplantation of a vascularized whole knee joint allotransplantation with autologous AV bundle implantation covered by a pedicled gracilis muscle flap in three outbred farm pigs. The complexity, expense and postoperative complications resulted in premature termination of the experiment. We conclude whole joint allotransplantation is an extremely complex surgical procedure, wherein our new model requires further development to establish a valid large animal model with reproducible results. Discussion Revascularization of conventional non-vascularized bone allografts, often cryopreserved (CBA), is a slow and incomplete process. Almost 40-50% of the interstitial lamellae remain avascular after two years [23-25] . In the past decades, autogenous vascularized bone grafts have been widely used. The advantage of this technique is better and faster incorporation of the graft [10, 26-30] . The free fibula flap has become the workhorse in clinical setting for the treatment of large segmental bone defects. However, the initial strength of the vascularized fibular graft may be insufficient in lower extremity reconstructions, due to small diameter of the bone. Although, hypertrophy often occurs at an average of 18 months after surgery, hypertrophic bone fractures have been reported [7, 31] . A vascularized fibula graft in the lower extremity should be protected against fatigue fracture in the first few years [32] . To solve these problems, Dr. Capanna introduced a new technique wherein the vascularized fibula graft is combined with a massive allograft to protect the fibula from mechanical loads (VBG + CBA) [12] . Alternatively, living bone and joint allotransplantation offers a novel method to reconstruct large segmental bone defects. Here we will discuss the different treatment modalities of using vascularized autogenous bone and vascularized composite allotransplantation of bone and joint. Mechanical stimulation or stress loading of bone is a major factor in the maintenance of normal balance between bone formation and resorption. This process can take place at different levels of the bone segment according to the individual characteristics and variation over time of the axial strain rate [7, 33, 34] . Increased mechanical load on long bones can produce a stimulus in which bone formation outpaces bone resorption [35] . Correspondingly, repeated mechanical load which exceeds the strength of the bone can cause stress fractures. Bone growth is evidenced in the areas where compression or traction load is increased, meanwhile decreasing load leads to resorption [34] . The ability of a vascularized or non-vascularized bone to resist and adapt to mechanical loading depends upon both its strength and viability [4, 36] .