Preservation Strategies for Vascularized Composite Allotransplantation: An Updated Systematic Review of a Rapidly...

Composite allotransplantation has become a viable reconstructive option for selected patients, but preservation remains a major barrier to broader clinical application. Static cold storage is the current gold standard, yet ischemia reperfusion injury and limited preservation times restrict its effectiveness. Recent advances in machine perfusion and subzero nonfreezing storage (or supercooling) have prompted renewed interest in optimizing graft viability.

Following PRISMA guidelines, we systematically searched PubMed, EMBASE, and Cochrane, covering studies published from June 2022 to August 2025 for studies on ex vivo preservation of vascularized composite allotransplantations. Eligible articles included original studies in English evaluating postharvest, pretransplant preservation strategies. Data extracted were study design, preservation methods, perfusates, and primary outcomes. Risk of bias was assessed using SYRCLE for animal studies and Joanna Briggs Institute for human/cadaver studies.

Seventeen studies met the inclusion criteria: 1 on static cold storage, 13 on machine perfusion, and 3 on supercooling. Static cold storage research has declined, with the only recent study investigating subnormothermic machine perfusion as a recovery adjunct. Machine perfusion studies focused on the optimization of perfusion parameters, perfusate composition, and circuit design. Red blood cell-based perfusates remained common, but alternative oxygen carriers such as polymerized hemoglobin-based oxygen carrier-201 and dextran oxygen microcarriers showed promise despite edema-related challenges. Supercooling studies demonstrated the feasibility of multiday preservation in rodent and porcine models. Overall, risk of bias was high or unclear across animal studies, mainly due to selection and performance bias, whereas the single human ex vivo study showed low risk of bias.

The field of vascularized composite allograft preservation is expanding rapidly, with a combination of static and dynamic techniques emerging as a promising option to extend graft viability beyond the current limits. However, translation to clinical setting remains limited by small preclinical studies, methodological heterogeneity, and the paucity of functional endpoints. Standardized protocols, robust large-animal models, and eventual human feasibility trials are needed to establish clinically applicable preservation strategies.