Dolph Houben

77 Outcomes of vascularized bone allotransplantation 4 Introduction Reconstruction of loss of large segments of bone is a challenging clinical problem. Current reconstructive options include the use of cryopreserved allografts, bone transport, prosthetic replacement, membrane-induced osteogeneses, re-implantation of autoclaved tumor bone and vascularized bone autografts, all with a significant incidence of complications and failure. Of these, the most successful are cryopreserved allografts and vascularized autogenous bone flaps. Banked bone may be matched to the bony defect, providing immediate stability without donor site morbidity. As they remain largely avascular over time, delayed or non-union is frequent, as are infection and late stress fracture [1-7]. Vascularized autografts are limited primarily to the fibula and iliac crest for large skeletal defects. They better promote healing and resist infection, but often fail to provide sufficient strength and/or stability for function, with the risk of early fracture. Other methods are less commonly used, with higher rates of complications and/or significant morbidity. Transplantation of living allogenic bone has the potential to combine the same biological benefits as vascularized autografts with the mechanical advantages provided by size- and shape-matched cryopreserved banked bone segments [8-10] . Practical use of vascularized composite allotransplantation (VCA) is limited by the need for life-long immunosuppression due to concerns of drug toxicity, expense, and complications with its use. The ability to maintain bone VCA viability without need for prolonged drug therapy would permit potential clinical use of size and shape-matched living bone for most any skeletal defect. The combination of microvascular repair of the allotransplant vascular supply with autogenous vessel implantation and two weeks of initial immunosuppression is a novel method to maintain allotransplant viability without the need for life-long immunosuppression. Successful results in small animal models have been encouraging [11-13] . A large animal model with similar success could lead to clinical application for segmental bone loss [11, 12, 14-22] . In this study, we report bone healing, remodeling and mechanical properties of bone-only VCAs using our previously described swine tibial defect model for this purpose [17, 18] . Methods Experimental Design This study was approved by the Institutional Animal Care and Use Committee. All experiments were performed according to the established National Institutes of Health guidelines. Sinclair provided 21 Yucatan miniature swine (Sinclair Bioresources, LLC), matching 7 donors of two tibiae each to 14 recipient animals. All were matched by age (mean 5.8 months), size (15-35kg) and blood type (type A). All had swine leukocyte antigen (SLA) haplotyping prior to beginning the experiment, ensuring that no donor-recipient pairings were SLA-identical. This mismatch was sufficient to lead to rejection and VCA necrosis should the autogenous angiogenesis method fail. All 14 recipient animals had segmental tibial defects created and reconstructed with immediate VCA transplantation from the chosen recipient, described below. Animals were divided into two groups of 7 each, differing only in the patency of a second vascular supply. An autogenous cranial tibial arteriovenous bundle (AV- bundle) was passed into the medullary canal of the VCA segment. In Group 1 the AV-bundle was patent and in Group 2, ligated. The survival period was 20 weeks.