Neo-Angiogenesis, Transplant Viability, and Molecular Analyses of Vascularized Bone Allotransplantation Surgery in a Large Animal Model

Rudolph H. Houben, Roman Thaler, Dimitra Kotsougiani, Patricia F. Friedrich, Alexander Y. Shin, Andre J van Wijnen, Allen T. Bishop

Research output: Contribution to journalArticle

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Abstract

Vascularized composite allotransplantation of bone is a possible alternative treatment for large osseous defects but requires life-long immunosuppression. Surgical induction of autogenous neo-angiogenic 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 allotransplantation tests its applicability in a pre-clinical large animal model. Previously, we have demonstrated bone vascularized composite allotransplantation (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 neo-angiogenesis control). At twenty weeks, we quantified the neo-angiogenesis 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 allotransplants of swine tibia maintained viability and actively remodeled over 20 weeks when short-term immunosuppression is combined with simultaneous autogenous neo-angiogenesis.

Original languageEnglish (US)
JournalJournal of Orthopaedic Research
DOIs
StateAccepted/In press - Jan 1 2019

Keywords

  • bone
  • experimental
  • neo-angiogenesis
  • reconstruction
  • vascularized composite allotransplantation (VCA)

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

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