Dolph Houben

18 CHAPTER 1 organ toxicity, wound healing problems, metabolic diseases, and high costs. Therefore, life-long immunosuppressive therapy is contraindicated in oncological patients and presents an ethical dilemma wherein it is questionable to use life-ling IS for non-life critical transplantations. In the past years, a novel method has been developed maintaining allotransplant viability without the need for life-long immunosuppression or induction of tolerance. Surgical angiogenesis combined with short-term IS may maintain VCA viability and has shown potential in small animal models. This novel method is therefore the key focus of our research. We will investigate methods of maintaining bone and joint VCA viability with short-term IS and surgical angiogenesis in a pre- clinical porcine model. Through this investigation, we will refine our understanding of bone healing, remodeling, mechanical bone properties, pedicle patency, AV bundle patency, local and systemical immune response, and osteocyte lining (transplant chimerism). Further, we will demonstrate the feasibility of the method to transplant allogeneic vascularized composite whole joints in a porcine model. An evaluation of clinical literature of VGBs and combined VBG with CBA reconstruction is also provided (Chapter 2 and 3). Aims and outline of the thesis The overall goal of this thesis is to microsurgically transplant living allogenic bone and joints and maintain viability without the need for life-long immunosuppression (IS) or tolerance induction in a pre-clinical model. In this thesis we further evaluate a novel method of maintaining VCA viability by switching the circulation of the allotransplant from allogeneic to autogeneic in a large animal model. This may be accomplished by combined microsurgical allotransplantation and simultaneous development of a new autogeneic blood supply in the allotransplant. Surgical implanted autogenous arteriovenous (AV) bundles will promote autologous neo-angiogenesis during the short-term immunosuppressive period. As this recipient-derived circulation is non- immunogenic, allotransplant viability will be maintained while the allogeneic circulation will thrombose due to rejection. Hypothesis 1: In clinical practice, segmental bone defects are best reconstructed with a vascularized autograft combined with or without a massive cortical allograft. Aim1: To study the history, indications, contra-indication, surgical technique and clinical outcomes of the vascularized fibula flap at the Mayo Clinic (Chapter 2). We will perform a literature search within Mayo Clinic published articles on the vascularized fibula flap for the reconstruction of segmental defects. Aim 2: To evaluate the clinical outcomes of a combined allograft and vascularized fibula flap reconstruction (Chapter 3). We will perform a systematic review on the use of combined massive allograft with intramedullary vascularized fibula flap for the reconstruction of large bone defects in the lower extremity.