New Hope for the Treatment of Severe Skin Injury: Genetically Engineered Porcine Skin Xenotransplantation

Treatments of severe skin injuries have long been a clinical challenge. Early excision of necrotic tissue and skin grafting are essential, yet their effectiveness is hampered by several issues. Autologous and allogeneic skin shortages, the high cost of tissue-engineered skin, and its failure to fully mimic natural skin architecture limit treatment options. Porcine skin is the ideal donor for skin xenotransplantation. It closely resembles human skin in anatomical structure and physiological function, has abundant availability, and involves fewer ethical concerns. Gene-editing technologies allow for the genetic modification of pigs, minimizing xenogeneic immune rejection and zoonotic pathogen transmission risks, thus enhancing the scalability of porcine skin xenotransplantation. This article reviews advantages and limitations of porcine skin as a xenogeneic skin graft, along with the latest preclinical and clinical research on porcine skin xenotransplantation, with a particular emphasis on genetically modified pigs. It aims to highlight the significant potential of gene-edited porcine skin xenotransplantation in treating severe skin wounds. Insights from skin xenotransplantation can also serve as a valuable reference for the development of other organ xenotransplantation. Trial Registration: ClinicalTrials.gov identifier: NCT03695939 and NCT06223269.