Experimental Swine Models for Vascularized Composite Allotransplantation and Immunosuppression: A Systematic Review and Case Report of a Novel Heterotopic Hemifacial Swine Model

Lifelong immunosuppression is necessary to prevent rejection in vascularized composite allotransplantation (VCA). Animal models play a pivotal role in developing innovative immunosuppressive strategies. This systematic review and case report focuses on the most impactful swine VCA models while offering insights gained from the Yale Swine Allotransplantation Vascularized Experiment (Y-SAVE). 22 studies on swine VCA models were included. Key swine breeds included SLA-matched and mismatched MGH miniature swine, Yucatan miniature swine, and outbred domestic swine. Transplantation models varied, with 10 (45%) using osteomyocutaneous flaps and only 2 (9%) involving hemifacial flaps. While 16 (73%) studies utilized heterotopic models, 5 (23%) relied on orthotopic models. Novel strategies such as preconditioning and localized drug delivery emerged, alongside immunosuppression regimens combining tacrolimus with experimental therapies. We further introduced a modified heterotopic hemiface VCA model, demonstrating its feasibility for studying immune dynamics in facial transplants while preserving oral function and enabling serial skin and mucosal biopsies. Overall, our review highlights a notable gap in models that specifically investigate facial VCAs. Given the unique immunological environment of facial allografts, models such as the heterotopic hemiface transplant may offer critical insights into immune mechanisms and may provide a platform for refining targeted immunosuppressive strategies.