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Composite tissue allotransplantation (CTA) constitutes one of the last frontiers of microsurgery. Prior to its clinical application, the long-term efficacy of modern immunotherapy must be tested in a pre-clinical CTA model. Based on the concept of osteomyocutaneous forearm flap, we developed a CTA flap model in swine. After identifying the vascular territory of the flaps in six pigs (vascular casting), flaps were transplanted from mismatched donor to recipient pigs (n = 6). Rejection was assessed daily by visual inspection and histopathology of biopsy specimens. Recipient pigs were able to ambulate immediately following surgery. There were no flap failures owing to technical or surgical complications. Rejection occurred over a period of 7 days as manifested by edema, cellular infiltration, epidermalysis, and thrombosis. This pre-clinical flap model is excellent for evaluating the effectiveness of modern immunotherapy because it is anatomically and immunologically relevant and because the minimal morbidity caused to the animal permits long-term studies.

Although vascularized bone and joint allotransplantation is a promising new treatment option for reconstructing large bone defects, the need for immunosuppressive agents to prevent rejection in these procedures poses a major problem. This problem stems from the fact that several of these agents can cause harmful side effects, such as alterations in bone quality and healing. Therefore, the purpose of this study was to determine what effect the commonly used immunosuppressant regimen cyclosporine A-based combination therapy has on bone quality and healing. In 10 pigs, vascularized bone allografts with skin and muscle components (osteomyocutaneous free flaps) were transplanted from size-matched donor animals. Recipient animals received oral cyclosporine A/mycophenolate mofetil/prednisone therapy for 90 days. Bone quality was studied before and after transplantation by measuring the bone's acoustic velocity and density and calculating the bone's elastic coefficient. Bone healing was assessed using radiographic analysis. Four animals were lost as a result of graft rejection or immunosuppression-related complications before the 90-day endpoint of the study. Although bone specimens taken from the six animals that completed the 90-day protocol had histological signs of rejection, they all seemed to have normal bone healing. Posttransplant bone density values were significantly decreased (p < 0.05) (1544.7 +/- 47.5 kg/m3) as compared with pretransplant values (1722.7 +/- 44.1 kg/m3). Results of the acoustic velocity and elastic coefficients measurements showed a significant decrease (p < 0.05) in posttransplant values (from 3503.0 +/- 165.1 meters/sec to 2963.0 +/- 54.6 meters/sec and from 21.6 +/- 2.2 GPa to 13.6 +/- 0.5 GPa, respectively), indicating diminished bone quality. The findings indicate that cyclosporine A/mycophenolate mofetil/prednisone combination therapy is ineffective in preventing bone rejection, that it decreases bone quality, and that it is associated with systemic toxicity, suggesting that this immunosuppressive regimen at the doses used in this study is not ideal for vascularized bone allotransplantation procedures.