Application strategies of autologous and decellularized nerve grafts: Structural and functional recovery

Autologous nerve transplantation is currently recognized as the gold standard for treating severe peripheral nerve injuries in clinical practice. However, challenges such as a limited supply of donors, complications in the donor area, and the formation of neuromas necessitate the optimization of existing transplantation strategies. Additionally, the development of new and promising repair methods is a critical issue in the field of peripheral nerve research. The purpose of this article is to compare the advantages and disadvantages of autologous, allogeneic, decellularized nerve grafts, and cell-composite graft, as well as to summarize the differences in their prognostic factors and associated adverse events. The length, diameter, polarity, and sensory or motor origin of autografts all influence axonal regeneration. While pre-denaturation treatment can accelerate early regeneration, long-term functional outcomes of autografts do not show significant differences compared with fresh autologous grafts. For decellularized nerve grafts, defect length is identified as an independent risk factor, and the internal microenvironment (delayed angiogenesis, Schwann cell senescence, and reduced T-cell infiltration) is considered a key factor limiting long-segment regeneration. Additionally, the decellularization process (whether chemical, physical, or supercritical CO 2 ) affects the integrity of the extracellular matrix and the presence of immune residuals, which directly impacts axonal guidance and host integration. Common adverse events following autograft transplantation include donor site numbness, neuromas, and scarring. In contrast, adverse events associated with decellularized nerve graft transplantation may present as inflammatory reactions, excessive scar proliferation, and misalignment or reconnection of regenerating axons, which can lead to sensory-motor cross-innervation. To mitigate these issues, combining decellularized nerve grafts with autologous Schwann cells, mesenchymal stem cells, or induced pluripotent stem cell- derived cells may help bridge the gap with autografts. However, the fact that structural recovery does not necessarily lead to functional recovery needs further clarification. Future research should establish large animal models to replicate the limits of human regenerative capacity, use gene editing to enhance the phenotype and microenvironment of transplanted cells, and develop a mild combined decellularization process that maximizes the preservation of natural nerve grafts. Through multidimensional optimization, decellularized nerve grafts have the potential to ultimately replace autograft transplantation, enabling precise repair of individualized, long-segment, and complex nerve defects.