Dolph Houben

16 CHAPTER 1 with IS [93-97] , and infusion of donor bone marrow-derived cells combined with antilymphocyte serum [98] are other proposed methods of inducing tolerance in allotransplantation for some period of time. All methods have serious drawbacks as the tolerant state is not maintained and graft-versus-host disease (GvHD) can occur which is potentially lethal [99-101] . Complete ablation of the recipient’s hematopoietic system by whole-body irradiation prior to allogeneic engraftment may minimize GvHD but is also potentially lethal [102] . The complications associated with tolerance induction are as onerous as those of immunosuppression. Therefore, current techniques to maintain allotransplant viability by tolerance induction or drug-therapy are impractical for clinical use. Other methods to maintain transplant viability without drug-therapy or tolerance induction need to be considered to make VCA a success as a possible alternative reconstructive method. Innovation Bone and/or joint VCAacceptancemay alsobe facilitatedby transplant chimerism, the replacement of the allogeneic bone with recipient-derived osteocytes [48, 103-105] . This is a novel method of maintaining bone and joint VCA viability without the need for either life-long immunosuppression (IS) or tolerance induction. The method replaces the allogeneic endosteal circulation with a recipient-derived neoangiogenic circulation. This is accomplished by the implantation of an autologous (recipient-derived) arteriovenous (AV) bundle into the intramedullary space, together with microvascular repair of the allogeneic nutrient vessels. Only short-term immunosuppressive drug therapy is required. During the short-term IS period, the implantation of autogenous AV bundle results in the rapid development of an autogenous neoangiogenic circulation. After cessation of the IS, the allogenic pedicle will eventually thrombose due to rejection. Angiogenesis or vasculogenesis is the biologic formation of new capillary vessel, mediated by growth factors, cell interactions, and proteolytic enzymes that modify molecules on cell surfaces and extracellular matrices [106] . Surgical angiogenesis is the transfer of vessels or well-vascularized autogenous tissue into an area of relative hypovascularity [107-110] . Surgical angiogenesis for the induction of a neoangiogenic circulation in autogenous bone was first described in a canine tibia model [109] . The implantation of AV bundles for the induction of new bone formation and revascularization have been shown in autograft [15, 108, 111, 112] , allograft [110, 113-117] , and xenograft bone [118, 119] . Clinical application of surgical angiogenesis has been described in avascular necrosis of the talus [109] , Kienbock’s disease [120, 121] , scaphoid non-union due to avascularity [122-124] , and prefabricated bone flaps [125] . Multiple small animal studies have been conducted on the use of surgical angiogenesis in maintaining bone and joint VCA viability. All demonstrate living bone allotransplants survive by surgical angiogenesis alone after cessation of the immunosuppression. The neo-angiogenic circulation, promotes new bone formation, maintains bone material properties and limb function[87, 110, 118, 126-134]. Multiple lineage studies evaluated areas of new bone formation and active remodeling. These studies demonstrated repopulation of the allotransplant by recipient-derived osteocytes over time which indicates transplant chimerism [134-136].