Electrical Stimulation-Induced Modulation of Small Extracellular Vesicles in Regenerative Therapy.

Abstract

Background: Small extracellular vesicles (sEVs) are nanoscale, membrane-bound vesicles mediating intercellular communication by transferring bioactive molecules, including nucleic acids, proteins, lipids, and metabolites. Electrical stimulation (ES) has emerged as a bioengineering strategy for modulating cellular electrophysiology, calcium signaling, and vesicle secretion. Although ES is increasingly recognized as a regulator of sEV biology, its effects on sEV biogenesis, cargo composition, and regenerative function have not been systematically defined. Therefore, this review aims to synthesize current evidence to clarify the influence of ES on sEV biogenesis, release, cargo remodeling, and functional outcomes in regenerative contexts.

Methods: Relevant published literature was reviewed to summarize current evidence on the effects of electrical stimulation on sEV biogenesis, secretion, cargo composition, and regenerative function. Articles were selected based on their relevance to ES-mediated sEV regulation, electrically responsive tissues, and regenerative medicine applications.

Results: The reviewed studies indicate that ES can regulate sEV secretion and alter molecular cargo profiles in a context-dependent manner. Evidence from diverse electroresponsive tissue-related systems suggests that ES-modulated sEVs may contribute to regenerative and tissue-protective responses.

Conclusions: This review summarizes current evidence on ES-mediated sEV modulation across electroresponsive tissues. Given remaining challenges in standardization and in vivo mechanistic validation, we propose future directions including advanced EV tracking and cell-type-specific analyses. Overall, ES-enabled sEV modulation represents a promising strategy for next-generation regenerative therapies.