Dynamic and Label-Free Sensing of Cardiomyocyte Responses to Nanosized Vesicles for Cardiac Oxidative Stress Injury Therapy.

Cardiac oxidative stress is a significant phenotype of myocardial infarction disease, a leading cause of global health threat. There is an urgent need to develop innovative therapies. Nanosized extracellular vesicle (nEV)-based therapy shows promise, yet real-time monitoring of cardiomyocyte responses to nEVs remains a challenge. In this study, a dynamic and label-free cardiomyocyte biosensing system using microelectrode arrays (MEAs) was constructed. Cardiomyocytes were cultured on MEA devices for electrophysiological signal detection and treated with nEVs from E. coli , gardenia, HEK293 cells, and mesenchymal stem cells (MSC), respectively. E. coli -nEVs and gardenia-nEVs induced severe paroxysmal fibrillation, revealing distinct biochemical communication compared to MSC-nEVs. Principal component analysis identified variations and correlations between nEV types. MSC-nEVs enhanced recovery without inducing arrhythmias in a H 2 O 2 -induced oxidative stress injury model. This study establishes a fundamental platform for assessing biochemical communication between nEVs and cardiomyocytes, offering new avenues for understanding nEVs' functions in the cardiovascular system.