EXPERIMENTAL ORTHOTOPIC TRANSPLANTATION OF VASCULARIZED SKELETAL ALLOGRAFTS - FUNCTIONAL ASSESSMENT AND LONG-TERM SURVIVAL

Vascularized skeletal tissue allografts would greatly expand the domai n of reconstructive surgery. Few studies to date have examined the fun ctional aspects of these allografts or their long-term fate. An orthot opic transplant model of rat distal femur and surrounding muscular cuf f was developed to assess graft function in fracture healing and weigh t bearing. Isografts (RT1(l) to RT1(l), n = 40), weak-barrier allograf ts (RT1(l) to RT1(lv), n = 40), and strong-barrier allografts (RT1(l) to RT1(n), n = 40) were transplanted. As the histocompatibility barrie r increased between the donor and recipient animals, the graft viabili ty and performance deteriorated according to radiographic, histologic, and immunologic analyses. Administration of cyclosporine led to survi val of strong-barrier allografts similar to that of isografts. A long- term study of these allografts (RT1(l) to RT1(n)) was then performed o n various immunosuppressive regimens. After an initial 10-week course of cyclosporine to achieve bony union and remodeling, subsequent cessa tion (n = 20) or intermittent ''pulsing'' (n = 20) of the immunosuppre ssant was insufficient in maintaining graft survival. However, graft v iability and function were preserved through 1 year on continuous dail y cyclosporine (n = 32). There was no evidence of host renal or hepati c toxicity by serum chemistry or histologic sections. Thus long-term s urvival of functional skeletal allografts was achieved in this orthoto pic model without significant host toxicity from immunosuppression.