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

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

Fingerprint

Vascularized Composite Allotransplantation
Tibia
Immunosuppression
Swine
Animal Models
Bone Remodeling
Transplants
Bone and Bones
Endothelial Growth Factors
Miniature Swine
Gene Expression
Osteocytes
Feasibility Studies
Immune System
Cell Count
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

Neo-Angiogenesis, Transplant Viability, and Molecular Analyses of Vascularized Bone Allotransplantation Surgery in a Large Animal Model. / Houben, Rudolph H.; Thaler, Roman; Kotsougiani, Dimitra; Friedrich, Patricia F.; Shin, Alexander Y.; van Wijnen, Andre J.; Bishop, Allen T.

In: Journal of Orthopaedic Research, 01.01.2019.

Research output: Contribution to journalArticle

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