Experimental vascularized bone allografting

Presented here is a compendium of studies investigating the fate of vascularized bone allografts. The first set of experiments employ the posterior rib graft in two canine models. The rib-to-mandible model was used to evaluate the rejection phenomena of vascularized bone allografts in an outbred dog model. This ascertained the time course of rejection and histological characteristics of the grafts. Immunosuppression of the graft recipients was attempted with azathioprine and cyclosporine. The results demonstrated that azathioprine was not an effective immunosuppressant, whereas cyclosporine resulted in survival of cortical osteons. The use of the vascularized rib allograft, with and without azathioprine, to bridge the defect in the dog femur was met with failure. Further studies employed a genetically defined rat model to determine the effect of different histocompatibilities on the survival of vascularized knee allografts. Grafts were transplanted from Lewis rats to syngeneic Lewis rats as isografts and to Fischer-344 rats (F-344) and Brown-Norway rats (BN) as allografts. Grafts across a major histocompatibility barrier to BN were rejected by 7 days, whereas grafts across a weak histocompatibility barrier to F-344 were rejected more slowly. The use of cyclosporine in this model abrogated the rejection response when administered to both groups continuously. However, a short course of cyclosporine was effective in preventing rejection in the F-344 animals. Efforts to induce tolerance by blood transfusions, from the donor strain or from a third-party donor, were not effective in preventing rejection.