Enabling dual excitation-contraction recording and disease modeling via hydrogel-free heart tissue

Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) are increasingly used to assess drug toxicity through effects on ion channels; however, contractility is not always evaluated. Interest in integrating contractility data from engineered heart tissue with electrophysiological signals to more comprehensively assess human cardiac responses is growing. In this study, we develop a scalable platform, a dual excitation-contraction (DEC) recording system, to generate engineered heart tissue without using collagen or fibrin gels. This device is compatible with commercial multi-electrode array systems and enables contractility data collection through optical observation. We validate the system using several drugs with varying torsade de pointes risks, underscoring the advantage of comprehensive, multi-parameter readouts over single-parameter analyses. Additionally, we use this device for disease modeling, such as myosin-binding protein C (MYBPC3) deficiency, and successfully replicate contractile deficits in the engineered heart tissues.