Cardiomyocyte-Based Multimodal Biosensing Platform for Dynamic Functional Assessment of Bioinspired Engineered Respiratory Virus-Induced Myocarditis

Respiratory virus-induced myocarditis (RVIM) represents an escalating clinical challenge, attributed to rising incidence and widespread viral infections such as influenza and severe acute respiratory syndrome. This type of myocarditis is commonly associated with malignant arrhythmias and acute cardiac dysfunction, demanding the sensitive diagnostic tools to detect the functional abnormalities at their early stages. Current diagnostic strategies that rely on cardiac biomarkers and imaging modalities, often lack the temporal resolution and specificity to identify subtle myocardial alterations during the initial phases of disease. Moreover, these approaches are constrained to dynamically reflect the electrophysiological changes and fail to adequately resolve the intercellular differences at high spatial resolution. Herein, we present a multimodal biosensing platform that integrates microelectrode array (MEA) electrophysiology with calcium imaging. This platform enables simultaneous and dynamic monitoring of electrical activity and calcium transients in multiple cardiomyocytes at single-cell resolution. Using an <i>in vitro</i> model of respiratory virus-infected cardiomyocytes, we observed that exposure to SARS-CoV-2 or H1N1 pseudoviruses induced abnormal electrical activities and calcium transients, indicating the impaired excitation-contraction properties. Notably, respiratory virus-infected cardiomyocytes treated with the calcium channel blocker nifedipine effectively restore from the abnormal state. This multimodal biosensing system constitutes a robust preclinical platform to facilitate dynamic monitoring of arrhythmic activity and explore the respiratory virus-associated myocardial dysfunction at early stages. Furthermore, this multifuntional platform supports high-throughput therapeutic screening and quantitative evaluation of pharmacological responses, offering a technically versatile framework for translational investigation.