From physical impact to biological information flow: shock wave regulation of extracellular vesicles mediated tissue...

Shock wave is a tunable pulsed mechanical stimulus that may modulate cellular behavior and tissue microenvironments during repair. However, how localized and transient mechanical inputs are translated into sustained paracrine or remote reparative responses remains incompletely understood. Extracellular vesicles, as mediators of intercellular communication after mechanical stress, may help convert local shock wave-induced cellular responses into transmissible biological signals. This narrative review summarizes current evidence on the shock wave-extracellular vesicle axis, focusing on extracellular vesicle release, cargo remodeling, and repair-associated functions. Available studies suggest that shock wave may promote extracellular vesicle secretion through mechanotransduction-related processes, including the ATP/P2X7R/p38 MAPK axis and nSMase2/ceramide signaling, while also altering microRNA-, protein-, and transcription factor-related cargo. Shock wave-induced or shock wave-preconditioned extracellular vesicles have shown potential pro-angiogenic, anti-apoptotic, antioxidative, immunomodulatory, and matrix-remodeling effects in experimental models of skin wounds, myocardial ischemia, myocardial ischemia-reperfusion, and diabetic bladder dysfunction. Overall, the shock wave-extracellular vesicle axis provides a candidate mechanistic framework for explaining part of shock wave-mediated tissue repair. Further studies should standardize shock wave parameters, improve extracellular vesicle characterization, and establish in situ tracing and causal validation.