Regulation of nanomaterials in peripheral nerve regeneration from a microenvironmental perspective: biological effects and mechanisms

The pathological microenvironment following peripheral nerve injury (PNI) comprises a dynamic interplay of cellular and molecular events that critically influence neuronal regeneration and functional recovery. Recent advances in nanotechnology have demonstrated the transformative potential of nanomaterials (NMs) in nerve repair, capitalizing on their unique physicochemical properties to engineer a pro-regenerative milieu that facilitates axonal regrowth. This review systematically explores the biological mechanisms by which NMs modulate and remodel the injury niche, thereby enhancing peripheral nerve regeneration (PNR). Specifically, this review highlights five key microenvironmental regulators, including rebuilding remyelinating Schwann cells, balancing the immune microenvironment, forming blood vessels, constructing extracellular matrix, and regulating cytokines and hormones. By analyzing these NMs-mediated therapeutic strategies, we provide novel mechanistic insights and discuss translational opportunities for next-generation nanomedicine in PNR therapy.