MicroRNAs Regulation of Axon Sprouting in Peripheral Nerve Regeneration: A Systematic Review.

Peripheral nerve injuries frequently result in long-term motor and sensory deficits, chronic pain, and incomplete functional recovery despite advances in surgical and rehabilitative approaches. MicroRNAs (miRNAs) have emerged as important post-transcriptional regulators of gene expression that influence axonal sprouting and peripheral nerve regeneration. This systematic review synthesizes current evidence on the roles of key miRNAs, particularly miR-21, miR-133b, miR-124, and miR-30b, in modulating critical signaling pathways including PI3K/Akt/mTOR and Rho/ROCK. These miRNAs contribute to axonal outgrowth, Schwann cell responses, and the resolution of inflammation. Preclinical studies demonstrate that miRNA-loaded exosomes and other delivery platforms can enhance neurite outgrowth and functional recovery in models of sciatic nerve injury. Various delivery systems, including viral vectors, polymeric nanoparticles, hydrogels, and engineered exosomes, have been investigated for targeted miRNA administration. Nevertheless, challenges related to the complexity of miRNA regulatory networks, efficient and specific delivery, and scalable production remain significant barriers to clinical translation. Overall, miRNA-based strategies represent a promising avenue for improving outcomes after peripheral nerve injury, provided that current limitations in delivery and specificity can be effectively addressed.