Electrically Conductive Collagen‐PEDOT:PSS Hydrogel Prevents Post‐Infarct Cardiac Arrhythmia and Supports hiPSC‐Cardiomyocyte Function

Abstract Myocardial infarction (MI) causes cell death, disrupts electrical activity, triggers arrhythmia, and results in heart failure, whereby 50–60% of MI‐associated deaths manifest as sudden cardiac deaths (SCD). The most effective therapy for SCD prevention is implantable cardioverter defibrillators (ICDs). However, ICDs contribute to adverse remodeling and disease progression and do not prevent arrhythmia. This work develops an injectable collagen‐PEDOT:PSS (poly(3,4‐ethylenedioxythiophene) polystyrene sulfonate) hydrogel that protects infarcted hearts against ventricular tachycardia (VT) and can be combined with human induced pluripotent stem cell (hiPSC)‐cardiomyocytes to promote partial cardiac remuscularization. PEDOT:PSS improves collagen gel formation, micromorphology, and conductivity. hiPSC‐cardiomyocytes in collagen‐PEDOT:PSS hydrogels exhibit near‐adult sarcomeric length, improved contractility, enhanced calcium handling, and conduction velocity. RNA‐sequencing data indicate enhanced maturation and improved cell‐matrix interactions. Injecting collagen‐PEDOT:PSS hydrogels in infarcted mouse hearts decreases VT to the levels of healthy hearts. Collectively, collagen‐PEDOT:PSS hydrogels offer a versatile platform for treating cardiac injuries.