Severe injuries of the face and limbs remain a major challenge in today's reconstructive surgery. Vascularized composite allotransplantation (VCA) has emerged as a promising approach to restore these defects. Yet, there are major obstacles preventing VCA from broad clinical application. Two key restrictions are (1) the graft's limited possible ischemia time, keeping the potential donor radius extremely small, and (2) the graft's immunogenicity, making extensive lifelong monitoring and immunosuppressive treatment mandatory. Machine perfusion systems have demonstrated clinical success addressing these issues in solid organ transplantation by extending possible ischemia times and decreasing immunogenicity. Despite many recent promising preclinical trials, machine perfusion has not yet been utilized in clinical VCA. This review presents latest perfusion strategies in clinical solid organ transplantation and experimental VCA in light of the specific requirements by the vascularized composite allograft's unique tissue composition. It discusses optimal settings for temperature, oxygenation, and flow types, as well as perfusion solutions and the most promising additives. Moreover, it highlights the implications for the utility of VCA as therapeutic measure in plastic surgery, if machine perfusion can be successfully introduced in a clinical setting.

Background Chronic rejection remains the Achilles heel in vascularized composite allotransplantation. Animal models to specifically study chronic rejection in vascularized composite allotransplantation do not exist so far. However, there are established rat models to study chronic rejection in solid organ transplantation such as allogeneic transplantation between the rat strains Lewis and Fischer344. Thus, we initiated this study to investigate the applicability of hindlimb transplantation between these strains to imitate chronic rejection in vascularized composite allotransplantation and identify potential markers. Methods Allogeneic hindlimb transplantation were performed between Lewis (recipient) and Fischer344 (donor) rats with either constant immunosuppression or a high dose immunosuppressive bolus only in case of acute skin rejections. Histology, immunohistochemistry, microarray and qPCR analysis were used to detect changes in skin and muscle at postoperative day 100. Results We were able to demonstrate significant intimal proliferation, infiltration of CD68 and CD4 positive cells, up-regulation of inflammatory cytokines and initiation of muscular fibrosis in the chronic rejection group. Microarray analysis and subsequent qPCR identified CXC ligands 9-11 as potential markers of chronic rejection.