Experimental Orthotopic Transplantation of Vascularized Skeletal Allografts

Abstract

Vascularized skeletal tissue allografts would greatly expand the domain of reconstructive surgery. Few studies to date have examined the functional aspects of these allografts or their long-term fate. An orthotopic transplant model of rat distal femur and surrounding muscular cuff was developed to assess graft function in fracture healing and weight bearing. Isografts (RT1l to RT1l, n = 40), weak-barrier allografts (RT1l to RT1lv, n = 40), and strong-barrier allografts (RT1l to RT1n, n = 40) were transplanted. As the histocompatibility barrier increased between the donor and recipient animals, the graft viability and performance deteriorated according to radiographic, histologic, and immunologic analyses. Administration of cyclosporine led to survival of strong-barrier allografts similar to that of isografts. A long-term study of these allografts (RT1l to RT1n) was then performed on various immunosuppressive regimens. After an initial 10-week course of cyclosporine to achieve bony union and remodeling, subsequent cessation (n = 20) or intermittent "pulsing" (n = 20) of the immunosuppressant was insufficient in maintaining graft survival. However, graft viability and function were preserved through 1 year on continuous daily cyclosporine (n = 32). There was no evidence of host renal or hepatic toxicity by serum chemistry or histologic sections. Thus long-term survival of functional skeletal allografts was achieved in this orthotopic model without significant host toxicity from immunosuppression.