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 Yong-Shik Shin, Allen Thorp Bishop

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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 (US)
Pages (from-to)160-166
Number of pages7
JournalMicrosurgery
Volume39
Issue number2
DOIs
StatePublished - Feb 1 2019

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Vascularized Composite Allotransplantation
Swine
Transplants
Bone and Bones
Tibia
Immunotherapy

ASJC Scopus subject areas

  • Surgery

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Bone vascularized composite allotransplantation model in swine tibial defect : Evaluation of surgical angiogenesis and transplant viability. / Kotsougiani, Dimitra; Hundepool, Caroline A.; Bulstra, Liselotte F.; Friedrich, Patricia F.; Shin, Alexander Yong-Shik; Bishop, Allen Thorp.

In: Microsurgery, Vol. 39, No. 2, 01.02.2019, p. 160-166.

Research output: Contribution to journalArticle

Kotsougiani, Dimitra ; Hundepool, Caroline A. ; Bulstra, Liselotte F. ; Friedrich, Patricia F. ; Shin, Alexander Yong-Shik ; Bishop, Allen Thorp. / Bone vascularized composite allotransplantation model in swine tibial defect : Evaluation of surgical angiogenesis and transplant viability. In: Microsurgery. 2019 ; Vol. 39, No. 2. pp. 160-166.
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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.",
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T1 - Bone vascularized composite allotransplantation model in swine tibial defect

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AU - Kotsougiani, Dimitra

AU - Hundepool, Caroline A.

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AU - Friedrich, Patricia F.

AU - Shin, Alexander Yong-Shik

AU - Bishop, Allen Thorp

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AB - 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.

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