Organ transplantation has progressed from a life-saving surgical intervention to a multidisciplinary field integrating immunology, bioengineering, and data science. Despite major advances in donor management, perioperative care, and immunosuppression, long-term graft survival remains limited due to chronic rejection, infection, and organ scarcity. Recent breakthroughs in organ preservation, particularly in hypothermic and normothermic machine perfusion, have enabled real-time graft assessment, metabolic reconditioning, and localized therapeutic delivery. Emerging precision immunomodulation strategies, including regulatory T-cell therapy, gene-edited cellular platforms, tolerogenic dendritic cells, and biomarker-guided minimization, are reshaping alloimmune control toward durable tolerance. Innovations in xenotransplantation, multigene-edited donor animals, and tissue biofabrication offer potential solutions to structural organ shortages, although they are accompanied by regulatory and ethical challenges. Artificial intelligence further enhances donor–recipient matching, risk prediction, and personalized immunosuppressive management. This review synthesizes advances in preservation technologies, immune engineering, cellular tolerance induction, artificial intelligence-driven decision support, and xenotransplantation and provides a comprehensive overview of the evolving transplant landscape. By integrating mechanistic insights into translational progress, we outline future pathways for regenerative, immune-educational, and precision organ medicine.
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