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

This study introduces a dual excitation–contraction (DEC) platform that forms hydrogel-free engineered human iPSC-derived 3D cardiac tissue on an aligned fibrous scaffold and enables concurrent electrophysiology and contractility readouts in a format compatible with planar multi-electrode array (MEA) systems. The chip supports formation of a small (~150 µm diameter) anisotropic 3D tissue that self-organizes from an initial monolayer and produces measurable mechanical beating alongside MEA field potentials. The authors validated the platform using multiple reference drugs spanning torsade de pointes (TdP) risk (e.g., isoproterenol, E4031, verapamil, ondansetron, azimilide), showing that contractile force and electrical endpoints can diverge (e.g., force becoming undetectable at verapamil doses where electrical activity persists) and that arrhythmogenic events (e.g., EADs) correspond to reduced force output. The system was further applied to disease modeling using MYBPC3-deficient iPSC lines, reproducing impaired systolic force generation and reduced capture at higher pacing frequencies, demonstrating utility for combined functional phenotyping and drug safety assessment.