In Silico Evaluation of Cardiac Tissue-Engineered Patch Interventions

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Abstract
Myocardial infarction significantly degrades heart function, and current treatments can bring forth serious cost and complications including blood clots and infections. To improve the current state of treatment, researchers are developing tissue patches from induced-pluripotent stem cells that can be incorporated into the heart, improving organ function after a myocardial infarction. These tissue patches include surface patches, attached to the epicardium of the heart, and thick transmural patches that replace the infarcted region. However, little is known about the impact of cardiac tissue patches on pump function in a patient's heart. In addition, it is not clear what patch structural properties - such as active stress generation, muscle fiber alignment, or material stiffness - may best augment existing heart tissue. Computational modeling can be used to examine different implementations and patch properties, illuminating the mechanical impact of cardiac tissue patches in the beating heart. In this work, we computationally implement different cardiac tissue patches to understand benefits of particular patch types and properties. We find that in transmural cardiac tissue patches, both activation and fiber alignment improve function. A transmural patch generating 10% of healthy active stress can increase stroke volume by 18%, and higher generated active stress in a circumferential muscle fiber orientation can recover stroke volume by over 50%. Furthermore, we find that surface cardiac tissue patches can enhance heart function slightly despite limiting diastolic filling, especially when fibrotic thinning has occurred. These conclusions identify broad design goals for the engineering of cardiac tissue patches to improve heart function after a myocardial infarction.
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