title: Host-derived neoangiogenesis with short-term immunosuppression allows incorporation and remodeling of vascularized diaphyseal allogeneic rabbit femur transplants.
abstract: The purpose of this study was to demonstrate that living bone allotransplants can incorporate, remodel, and maintain mechanical properties without long-term immunosuppression in a fashion comparable to living autotransplants. For this, viability is maintained by repair of nutrient vessels and neovascularization from implanted host-derived vasculature. Microsurgically revascularized femoral diaphysis allotransplants were transferred from young male New-Zealand-White (NZW) into 4 groups of male Dutch-Belted (DB) rabbits. Short-term immunosuppression by tacrolimus (IS, groups 4 and 5) and host-derived neovascularization (NV) from implanted fascial flaps was used to maintain viability (groups 3 and 5) as independent variables. Group 2 received neither IS nor NV. Vascularized pedicled autotransplants were orthotopically transplanted in group 1. After 16 weeks, transplants were evaluated using radiologic, histologic, biomechanical, and histomorphometric parameters. Vascularized bone allotransplants treated with both short-term IS and host-derived NV (group 5) healed in a fashion similar to pedicled autotransplants (group 1). Their radiographic scores were higher than other groups. Groups with patent fascial flaps (3 and 5) showed significantly greater neoangiogenesis than ligated controls (2 and 4). Tacrolimus administration did not affect neoangiogenesis. Elastic modulus and ultimate stress were significantly greater in autogenous bone than in allotransplanted femora. Biomechanical properties were not significantly different among allotransplants. Bone turnover was decreased with IS, but increased with NV by the implanted fascial flaps. Living allogeneic femoral allotransplants treated with short-term IS and host-derived neoangiogenesis can lead to stable transplant incorporation in this rabbit model. The combination of both factors optimizes bone healing. Transplant mineralization is improved with neoangiogenesis but diminished with IS.
authors.affiliation: Microvascular Research Laboratory, Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: Goetz A
authors.initials: GA
authors.lastname: Giessler
authors.forename: Mark
authors.initials: M
authors.lastname: Zobitz
authors.forename: Patricia F
authors.initials: PF
authors.lastname: Friedrich
authors.forename: Allen T
authors.initials: AT
authors.lastname: Bishop
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001847:Bone Diseases / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000601:surgery; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology*; D016025:Bone Transplantation / Q000379:methods*; D018483:Diaphyses / Q000098:blood supply / Q000502:physiology / Q000637:transplantation; D005269:Femur / Q000098:blood supply / Q000502:physiology / Q000637:transplantation*; D017102:Fracture Healing / Q000187:drug effects / Q000502:physiology; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D013524:Surgical Flaps / Q000098:blood supply; D016559:Tacrolimus / Q000494:pharmacology*; D014057:Tomography, X-Ray Computed; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus