Generation and Culture of Cardiac Microtissues in a Microfluidic Chip with a Reversible Open Top Enables Electrical Pacing, Dynamic Drug Dosing and Endothelial Cell Co‐Culture

Abstract Cardiovascular disease morbidity has increased worldwide. Organs‐on‐chips and human pluripotent stem cell (hPSC) technologies aid to overcome some of the limitations in cardiac in vitro models. Here, a bi‐compartmental, monolithic heart‐on‐chip device that facilitates porous membrane integration in a single fabrication step is presented. Moreover, the device includes open‐top compartments that allow facile co‐culture of hPSC‐derived cardiomyocytes and human adult cardiac fibroblast into geometrically defined cardiac microtissues. The device can be reversibly closed with a glass seal or a lid with fully customized 3D‐printed pyrolytic carbon electrodes allowing electrical stimulation of cardiac microtissues. A subjacent microfluidic channel allowed localized and dynamic drug administration to the cardiac microtissues, as demonstrated by a chronotropic response to isoprenaline. Moreover, the microfluidic channel can also be populated with human induced pluripotent stem‐derived endothelial cells allowing co‐culture of heterotypic cardiac cells in one device. Overall, this study demonstrates a novel heart‐on‐chip model that systematically integrates an open‐top device with a 3D printed carbon electrode for electrical pacing and culture of cardiac tissues while enabling active perfusion and dynamic drug dosing. Advances in the engineering of human heart‐on‐chip models represent an important step towards making organ‐on‐a‐chip technology a routine aspect of preclinical cardiac drug development.