Bone vascularized composite allotransplantation model in swine tibial defect: Evaluation of surgical angiogenesis and transplant viability.

Abstract

In prior small animal studies, we maintained vascularized bone allotransplant viability without long-term immunotherapy. Instead, an autogenous neoangiogenic circulation is created from implanted vessels, sufficient to maintain bone viability with only 2 weeks immunosupression. Blood flow is maintained despite rejection of the allogeneic vascular pedicle thereafter. We have previously described a large animal (swine) pre-clinical model, reconstructing tibial defects with vascularized tibial allotransplants. In this manuscript, autologous angiogenesis is evaluated in this model and correlated with bone viability. Allogeneic tibial segments were transplanted across a major swine leukocyte antigen mismatch. Microvascular repair of the bone VCA pedicle was combined with intraosseous implantation of an autogenous arteriovenous (AV) bundle. The bundle was ligated in group 1 (n = 4), and allowed to perfuse in group 2 (n = 4). Three-drug immunotherapy was given for 2 weeks. At 16 weeks micro-CT angiography quantified neoangiogenic vessel volume. Bone viability, rejection grade, and bone healing were analyzed. A substantial neoangiogenic circulation developed from the implanted AV-bundle in group 2, with vessel density superior to ligated AV-bundle controls (0.11 ± 0.05 vs. 0.01 ± 0.01, P = .029). Bone allotransplant viability was also significantly enhanced by neoangiogenesis (78.7 ± 4.4% vs. 27.7 ± 5.8%, P = .028) with higher bone healing scores (21.4 ± 2.9 vs. 12.5 ± 3.7, P = .029). Ligated control tibias demonstrated disorganized bone morphology and higher local inflammation (P = .143). Implantation of autogenous AV bundles into vascularized bone allotransplants resulted in the rapid formation of a neoangiogenic autogenous blood supply in a swine tibia model that maintained bone viability, improved bone healing, and minimized rejection.