Where Do We Stand for Nerve Regeneration and Functional Recovery After Vascularized Composite Allotransplantation?

ABSTRACT Introduction Vascularized composite allotransplantation (VCA) offers a reconstructive solution for patients with severe limb and facial defects by transplanting multiple tissue types—including skin, muscle, bone, and nerves—as a single unit. This review examines current challenges in nerve regeneration and functional recovery following VCA, and assesses emerging strategies aimed at overcoming these hurdles. Methods A comprehensive literature review was conducted, focusing on clinical outcomes from upper limb and facial transplantation programs worldwide. Studies evaluating rehabilitation protocols, transplantation levels, follow‐up durations, and experimental strategies (cellular therapies, biomaterials, and neurotrophic factor delivery) were analyzed to determine their impact on nerve regeneration and functional recovery. Results Clinical evidence indicates that while protective sensation can return within months after VCA, motor function recovery often extends over several years. Variability in outcomes has been noted, largely due to differences in rehabilitation practices, assessment metrics, and follow‐up duration. Experimental approaches, including stem cell‐based therapies—especially those using adipose‐derived stem cells—demonstrate potential for enhancing axonal regeneration and modulating immune responses, although the long‐term benefits and standardized measures remain to be fully established. Conclusions Despite promising advancements in surgical techniques and immunosuppressive regimens, effective nerve regeneration in VCA remains a significant challenge. The variability in clinical outcomes underscores the need for standardized functional assessment protocols and further research into novel regenerative therapies. Future studies should focus on refining these therapeutic strategies to improve long‐term functional recovery and minimize the reliance on chronic immunosuppression.