Abstract Body: During myocardial infarction (MI), up to 1 billion cardiomyocytes (CMs) die, leading to permanent muscle loss and devasting functional outcomes. For decades, biomaterial therapies have been used to restrain the infarcted left ventricle (LV), reduce ventricular wall stress, limit dilation, and maintain global cardiac function. However, how these biomaterials alter regional mechanics and LV remodeling is poorly understood, and they fail to directly address contractile deficits due to the loss of CMs. In this study, an optimized therapeutic implant is designed to provide both mechanical support from a biomaterial scaffold and contractile CMs in an engineered tissue to promote cardiac function after MI, informed by computational simulations. A finite element model of the LV post-MI showed that a longitudinally aligned fibrous material (modeled after polycaprolactone, PCL) and active implant contraction improve calculated LV ejection fraction post-MI by +3.4% and +15.0%, respectively. To this end, we developed a composite remuscularization-reinforcement therapy by combining engineered cardiac tissue (ECT) composed of human induced pluripotent stem cell-derived CMs (hiPSC-CMs) in a collagen-1 hydrogel with highly aligned electrospun PCL fibrous scaffolds. Remuscularization (i.e. ECT-only), reinforcement (i.e. PCL-only) and dual therapy (PCL+ECT) were assessed in a rat model of permanent ligation MI with immediate implantation of the therapeutic. Implanted hiPSC-CMs significantly mature over 4 weeks, shown by an increase in myofilament area (~7-fold) and ventricular myosin light chain 2 (~2-fold). Longitudinal 4D ultrasound reveals dynamic changes in 3D regional strain (a measure of contractility) in the injured wall over 4 weeks. PCL alone supports maintenance of almost 80% surface area (SA) strain acutely (day 3) but strain diminishes through 4 weeks. ECT alone enables SA strain recovery from day 3 to >70% of baseline at weeks 1 and 2. The dual PCL+ECT therapy has SA strain preserved at day 3 and improved at 1, 2, and 4 weeks, maintaining higher strain globally at 4 weeks versus all other groups. Our high resolution contractility results support the development of an aligned PCL scaffold with hiPSC-CM ECT as a cell-based therapy to reinforce, remuscularize and re-engineer the function of the heart post-MI.