Extracellular vesicles and their cargo molecules for peripheral nerve injuries and neuropathies: The composition, properties, and impact

Peripheral nerve repair remains a major clinical challenge due to limited functional recovery and the lack of effective therapeutic options. Extracellular vesicles (EVs) have emerged as potential mediators of nerve regeneration due to their roles in cell-to-cell communication and the delivery of diverse bioactive molecules. The regenerative potential of EVs largely depends on the type of cell they originate from, which determines their molecular cargo and therapeutic potential. This review provides a comprehensive and focused analysis on the source-specific composition of EVs, and how different EVs distinctly influence neuroprotective, immunomodulatory, and neuroregenerative properties with direct relevance to peripheral nerve injury (PNI). We also highlight current evidence on how EVs modulate nerve repair pathways and discuss the implications of their source-specific content in optimizing EV-based therapies alongside recent technological advances for PNI. By highlighting key differences in regenerative-associated signaling, this review provides insight into optimizing EV-based therapies for PNI and outlines prospects for clinical application.