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

Dimitra Kotsougiani, Caroline A. Hundepool, Liselotte F. Bulstra, Patricia F. Friedrich, Alexander Y. Shin, Allen T. Bishop*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Scopus)
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Abstract

Introduction: 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. Materials and methods: 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. Results: 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). Conclusion: 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.

Original languageEnglish
Pages (from-to)160-166
Number of pages7
JournalMicrosurgery
Volume39
Issue number2
Early online date5 Mar 2018
DOIs
Publication statusPublished - Feb 2019
Externally publishedYes

Bibliographical note

Funding Information:
This work is supported by a generous gift from Tarek E. Obaid. The German research foundation (Deutsche Forschungsgemeinschaft) (DFG grant: Ko 4903/1-1) provided salary support for Dr. Kotsou-giani. The authors report no conflict of interest. The authors thank Mrs. Teresa Decklever from the Mayo Clinic Small Animal Imaging Core and Mr. Jim Herrick, Mr. Robert and Mrs. Donna Lewis from the Bone Histomorphometry Laboratory, Mayo Clinic Rochester for their contributions for this work. We thank Hilal Maradit Kremers from the Department of Health Sciences Research of Mayo Clinic Rochester for the statistical help.

Publisher Copyright:
© 2018 Wiley Periodicals, Inc.

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