Scalable Bioelectronic Production of Extracellular Vesicles for Cardiac Tissue Regeneration

EV-based therapies are hindered by low production efficiency and poor scalability. Conventional methods to enhance EV yield-such as hypoxia or chemical stimulation-often compromise vesicle quality and cell health. This study introduces a bioelectronic platform featuring a planar interdigitated electrode array that enables simultaneous low-voltage (±1 V), low-frequency (2 Hz) biphasic stimulation and real-time super-resolution imaging of EV biogenesis via TIRF microscopy. This bioelectrical stimulation on primary cardiac cells significantly increases EV secretion without affecting cell viability. The resulting electrically-induced EVs (e-EVs) exhibit enhanced microRNA cargo-loading capacity, preserved tissue tropism, and functional therapeutic potential. In a murine model of acute myocardial infarction, miRNA-loaded e-EVs improved cardiac function and reduced fibrosis. These results highlight the potential of bioelectronic modulation as a scalable, non- destructive strategy for improving EV yield and functional performance in translational regenerative medicine.