Dolph Houben

96 CHAPTER 5 Abstract Vascularized composite allotransplantation of bone is a possible alternative treatment for large osseous defects but requires life-long immunosuppression. Surgical induction of autogenous neoangiogenic circulation maintains transplant viability without this requirement, providing encouraging results in small animal models [1-3] . A preliminary feasibility study in a swine tibia model demonstrated similar findings [4, 5] . This study in swine tibial allotransplantion tests its applicability in a pre-clinical large animal model. Previously, we have demonstrated bone VCA survival was not the result of induction of tolerance nor an incompetent immune system [1] . Fourteen tibia vascularized bone allotransplants were microsurgically transplanted orthotopically to reconstruct size-matched tibial defects in Yucatan miniature swine. Two weeks of immunosuppression was used to maintain allotransplant pedicle patency during angiogenesis from a simultaneously implanted autogenous arteriovenous bundle. The implanted arteriovenous bundle was patent in group 1 and ligated in group 2 (a no-angiogenesis control). At twenty weeks, we quantified the neoangiogenesis and correlated it with transplant viability, bone remodeling and gene expression. All patent arteriovenous bundles maintained patency throughout the survival period. Micro-angiographic, osteocyte cell count and bone remodeling parameters were significantly higher than controls due to the formation of a neo-angiogenic autogenous circulation. Analysis of gene expression found maintained osteoblastic and osteoclastic activity as well as a significant increase in expression of endothelial growth factor-like 6 ( EGFL-6) in the patent arteriovenous bundle group. Vascularized composite allotransplantation of swine tibia maintained viability and actively remodeled over 20 weeks when short-term immunosuppression is combined with simultaneous autogenous neoangiogenesis. These results are consistent with those seen in prior animal studies confirming maintenance of bone homeostasis and viability without the need of long-term immunosuppression.