Dolph Houben

175 Summary and general discussion 9 fibula as a method for the primary reconstruction of segmental bone defects in the lower extremity provides a single step reconstruction with good functional long-term outcomes. This technique has a primary union rate of 86.5%, with a high re-operation and complication rate (Chapter 3). This technique should especially be considered in tumor cases, since there is little evidence in literature for its use in traumatic or congenital defect cases. In conclusion, the use of autogenous vascularized bone grafts remains the gold standard for large segmental bone defects in the lower extremity with or without the use of a protective massive allograft shell. Primary union rates are significantly higher compared to non-vascularized massive allografts alone. Vascularized bone grafts are limited by the few expendable donor sites and donor site complications. Part II: In the second part of the thesis we focused on a new experimental reconstructive method: living bone allotransplantation, which is a form of vascularized composite allotransplantation (VCA). While VCAs are currently limited by the use of life-long immunosuppression, we developed a new experimental method to maintain bone VCA viability. This novel method of living bone allotransplantation combines the microvascular repair of the nutrient circulation with implantation of recipient-derived arteriovenous (AV) bundles with short-term immune modulation. We hypothesized that bone VCA viability can be maintained in a large animal model using surgical angiogenesis and short-term immunosuppression without tolerance induction or other permanent immune modulation. Instead, new bone formation in transplanted allogeneic bone is the result of transplant chimerism. In Chapter 4 , we demonstrated the ability to orthotopically transplant bone-only VCAs across a major histocompatibility barrier using sex-mismatched Yucatan miniature swine, implanting an AV-bundle within the medullary canal to induce recipient-derived angiogenesis (surgical angiogenesis). Two weeks of immunomodulation were used. We implanted a patent AV-bundle in group 1 and a ligated AV bundle in group 2 as a no-angiogenesis control. In both groups, a microsurgical repair of the nutrient vessel was performed in the recipient, combined with rigid internal fixation of the allotransplant. We successfully performed 12 vascularized bone allotransplantations. Over a 20-week period, pigs gained an average of 20 kg (40 kg final weight) and full-weight bearing was observed without exception by four days after operation. In this study, we found new periosteal bone formation and subsequent bone healing to result from blood flow through the microsurgically repaired allogenic vascular pedicle, confirmed by allogenic pedicle patency in the first 4-6 weeks after transplantation. The implantation of an autogenous AV bundle has no adverse effect on material properties but has a positive effect on bone remodeling of endosteal surfaces despite thrombosis of the allogenic pedicle.