TY - JOUR
T1 - Bone vascularized composite allotransplantation model in swine tibial defect
T2 - Evaluation of surgical angiogenesis and transplant viability
AU - Kotsougiani, Dimitra
AU - Hundepool, Caroline A.
AU - Bulstra, Liselotte F.
AU - Friedrich, Patricia F.
AU - Shin, Alexander Y.
AU - Bishop, Allen T.
N1 - Publisher Copyright:
© 2018 Wiley Periodicals, Inc.
PY - 2019/2
Y1 - 2019/2
N2 - 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.
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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U2 - 10.1002/micr.30310
DO - 10.1002/micr.30310
M3 - Article
C2 - 29504151
AN - SCOPUS:85061382481
SN - 0738-1085
VL - 39
SP - 160
EP - 166
JO - Microsurgery
JF - Microsurgery
IS - 2
ER -