Dolph Houben

134 CHAPTER 7 Abstract Background: Transplantation of living allogeneic bone segments may permit reconstruction of large defects, particularly if viability is maintained without immunosuppression. Development of a new autogenous osseous blood supply accomplishes this goal in rodent experimental models. This study evaluates potential systemic and local inflammatory responses to such angiogenesis in a large animal model. Methods: Vascularized allogeneic tibia segments were transplanted orthotopically into matched tibial defects in Yucatan minipigs. Microvascular anastomoses of bone nutrient artery and vein were supplemented by intramedullary placement of an autogenous arteriovenous (AV) bundle in Group 1. Group 2 served as a no-angiogenesis control. A 3-drug immunosuppression regimen was discontinued after 2 weeks. During the 20-week survival period, periodic leucocyte counts, and inflammatory cytokine levels were measured. Thereafter, osteocyte survival was quantified, and transplant rejection graded by histology and RT-qPCR of immunological markers. Results: Both groups developed an initial systemic response, resolved after 4-6 weeks. No differences were seen in blood cytokine levels. IL-2 expression was diminished in Group 1 tibiae. As expected, nutrient pedicles had thrombosed without sustained immunosuppression, occluded by intimal hyperplasia. In Group 1, angiogenesis from the autogenous AV-bundle resulted in significantly less osteonecrosis (p=0.04) and fibrosis (p=0.02) than Group 2 allotransplants. Conclusion : Systemic immune responses to large bone allotransplants were not increased by generation of an autogenous osseous blood supply within porcine tibial bone allotransplants. Implanted AV bundles diminished inflammation and fibrosis, and improved bone viability when compared to no-angiogenesis controls.