This proposal extends research into the biology of vascularized and nonvascularized bone grafts in a canine model in continuation of a long-term study, and in light of recent findings. Autografts and allografts, vascularized and nonvascularized, will be exchanged across carefully defined histocompatibility barriers. Cyclosporin-A will be further evaluated as an immunosuppressant in this context. Vascularized allografts, carefully matched at the major histocompatibility site, will be studied for their mechanical, morphological and biochemical properties at 3 and 6 months post-transplantation. The role of the Class I and Class II histocompatibility antigens will be evaluated in terms of the fates of both vascularized and nonvascularized grafts and also in terms of the immune responses generated by each of these kinds of grafts. Finally, a study will be undertaken to determine optimal parameters for the storage of bone destined for vascularized grafting. A unique feature of this project is the unusually thorough evaluation which will describe intermediate and end-points of acceptance of the grafts by their hosts. Specifically, these include (a) metabolic dynamics of bone calcium and collagen in pre-labelled animals; (b) measurement of mechanical properties of the grafts; (c) morphological evaluation by means of conventional histology, quantitative histomorphometry, and radiography; (d) immunological evaluation by means of conventional antibody and cell-mediated immunity measurements, by matching and careful control of genetic characteristics (MHC) of donor and recipient, and by use of selective methods of immunosuppression. Correlation of the first three parameters with each other as functions of the immunological measurements should provide useful perspectives in relating each of these parameters to the host response to the graft. In view of the very slow total acceptance of bone grafts, studies such as these should be extended over a longer period of time to yield the ultimate data on the fate of the grafts. This present proposal comprehensively evaluating critical biological and physical parameters should provide guidance for the future in regard to the role vascularized bone transplantation may play in clinical practice.
