A PEDOT:PSS-MWCNT-modified MEA platform with integrated electrical stimulation for enhanced maturation and drug screening of iPSC-cardiomyocytes

Abstract

Cardiovascular toxicity is a key safety indicator that has to be evaluated in the process of new drug development. To enable high-throughput and multiparametric assessment of cardiomyocyte function, we developed a 32-well high-throughput microelectrode array (MEA) platform integrated with electrical stimulation. Electrode surface modification with PEDOT:PSS-MWCNT nanocomposites significantly enhanced electrochemical performance and signal acquisition fidelity, reducing electrode impedance by 37-fold compared to unmodified Au electrodes. Notably, the built-in electrical stimulation effectively promoted electrophysiological and structural maturation of human iPSC-cardiomyocytes, demonstrated by a 15.47% increase in sarcomere length and 1.73-fold upregulation of connexin-43 expression. The platform's utility was further validated through cardiotoxicity assessment of two representative ion channel modulators, E-4031 (a selective hERG channel blocker) and verapamil (a clinically used calcium channel blocker). Collectively, this study presents an integrated platform that combines functional monitoring with cellular maturation enhancement, offering a powerful tool for cardiotoxicity screening and disease modeling.