Dolph Houben

179 Summary and general discussion 9 and stability, while maintaining the biological properties of VBGs. The distinct difference between the two methods is that VCAs do not requiring a donor site. Allotransplantation of complete knee joints is a novel approach to knee replacement surgery. Vascularized composite allotransplantation of bone and joint has been performed clinically [39, 40] . In these case series, multi-organ donors were used after explantation of vital organs. After harvest, the knee joint VCA was adjusted to fit the defect of the recipient on a back table. After transplantation and anastomosis of the vascular pedicle, internal fixation was performed by retrograde placed intramedullary nails. After initial success, all knee joint VCA attempts failed. In four patients, the VCA was rejected and had to be partially removed. Subsequently, a total knee arthroplasty was performed which led to an infection and eventually amputation [40] . Long- term immunosuppression and loss of transplant viability due to rejection should be alternatively managed to make allotransplantation of whole knee joints a success. Whole knee joint allotransplantation using our novel method of maintaining VCA viability by surgical neo-angiogenesis without the use of life-long immunosuppression has been evaluated in a rabbit model. Surgical neo-angiogenesis resulted in improved viability, bone remodeling, and bone properties. Flexion contractures, due to in part to the hyperflexed resting stance of the rabbit knee, caused functional impairment [41, 42] . The desirability to perform this type of VCA research in a large animal would facilitate thorough investigation of whole knee joint VCA feasibility, including bone healing, joint properties, tissue perfusion, as well as systemic and local immune responses. Although the porcine tibia defect model has proven to be of great value for bone-only VCA research, the novel large animal model for knee joint VCA research needs to be further developed. The surgical ability to successfully perform whole knee joints has been confirmed by both experimental and clinical studies [43, 44] . Post-operative management however should be adjusted and further studied. In the ideal world the application of living bone and joint allotransplantation would be further evaluated in an experimental follow-up study. For bone-only allotransplantation, I would like to see value and issues with allotransplantation versus current treatment. I would probably do a long-term survival experiment comparing conventional reconstruction with cryopreserved bone versus bone allotransplantation in pig model using our novel method of maintaining transplant viability. Second, I would like to see value and issues with surgical angiogenesis versus usual VCA methods, compare bone allotransplants with long-term IS versus our novel method, also with long-term survival in pig model. For whole joint allotransplantation I would like to do an experimental follow-up study in which we transplant an entire knee joint and optimize the post- operative care by using drains and provide support by using an abdominal sling. When we have a working and validated joint allotransplantation model, we can compare non-viable allograft whole joint with vascularized allotransplantation whole joint in a pig model. Although this type of research would greatly facilitate further development and pre-clinical data to safely translate the results to clinical setting. There are several major limitations to this type of research, the expense related to immunosuppressive drugs and long-term survival time of large animals are a major concern. Additionally, pigs are intelligent animals who are hard to compel to take their drugs for an extended period of time.