Enhancing cardiomyocyte maturation through PEDOT:PSS-coated surfaces and mechanical stimulation with strain sensors

Abstract Drug-induced cardiac toxicity is a critical concern in drug development, often leading to unreliable results and potential drug withdrawal due to the lack of mature cardiomyocytes in screening assays. This study aimed to enhance cardiomyocyte maturation by combining structural and conductive stimuli, specifically using a Poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) coated conductive PDMS membrane and a mechanical stimulation (MS) system. A 10% tensile strain at a frequency of 1 Hz was applied via a stepper motor controlled by an Arduino-based system, with real-time monitoring through an integrated strain sensor. The highly stretchable PEDOT:PSS strain sensor was incorporated into the well-placed surface to ensure precise MS. The functional well plate, featuring PEDOT:PSS-coated conductive microgrooves, was designed to align cardiomyocytes and promote the expression of maturation markers, including α -actinin and connexin43 (Cx43). Results showed that the combination of 10% mechanical strain and a conductive PEDOT:PSS surface significantly increased sarcomere length and Cx43 intensity compared to controls. This approach provides a more physiologically relevant environment for cardiomyocyte development, offering a more accurate model for assessing drug-induced cardiotoxicity in preclinical drug screening.