Dolph Houben

89 Outcomes of vascularized bone allotransplantation 4 hypertrophy of the arterial wall [38] . The resulting vasculopathy causes transplant ischemia, as previously observed in clinical transplantation studies [38-40] . In this study, the neoangiogenic autologous vessels will not be similarly affected. This not only leads to drug-free VCA survival but results in gradual repopulation of the bone with autogenous osteocytes in areas of active new bone formation [15, 41-44] . We did not see any significant beneficial or adverse effects of AV-bundle patency on bone material properties. It may be that a 20-week evaluation point is insufficient to detect a significant effect on material properties [16, 45] . However, the implantation of a patent AV-bundle increased the bone formation rate measured 20 weeks after transplantation on endosteal surfaces. This indicates that the recipient-derived neoangenic circulation through the implanted AV-bundle does have a positive effect on bone remodeling. These findings are similar to our preliminary study [17] . The close proximity of the implanted AV-bundle to endosteal surfaces likely allows delivery of autogenous osteoprogenitor cells as well as osteogenic and angiogenic signaling molecules, improving bone remodeling and new bone formation. In a previous rat study of femoral allotransplantation using sex-mismatched donors and recipients, we demonstrated that the cells located in areas of new bone formation are autogenous rather than surviving allogenic cells [16] . Experimental results of orthotopic allotransplantation of bone in a large animal model have never been reported in these large numbers. The expense and technical difficulty of the allotransplantation procedure and subsequent evaluations are probable reasons. Bone healing with new periosteal bone formation from the allotransplant suggests short-term immunosuppression is sufficient to promote healing of large segmental defects reconstructed with living bone allotransplants. In addition, the implanted AV-bundle significantly improves the remodeling properties on endosteal surfaces of the allotransplant. Extensive remodeling of bone would be required to observe either a negative or a positive effect and may require a longer survival time to be adequately assessed [16, 45] . Ultimately, the goal of this research would be application of bone-only VCA to patient care. Clinical experience with bone and joint only VCAs is limited. The largest experience, from a German group, included three femoral diaphysis and five whole knee allotransplantations [46-52] . Another study transplanted a fibula from mother to child [53] . All but the latter report eventually failed due to infection, acute rejection, or chronic allotransplant vasculopathy [38, 47, 54] . None used autogenous angiogenesis nor current VCA drug regimens, however. The time may be ripe for carefully controlled experimental clinical trials of bone VCA reconstruction of segmental bone loss. Segmental defects in the extremities occur most commonly in limb-sparing tumor surgery, but also due to traumatic loss, infection or congenital anomaly. While long-term drug treatment would be contraindicated for some of these indications, short-term immunosuppression would likely allow bone VCA reconstruction using our method.