Postinfarction treatment using multifunctional cardiac patch with cardiomyocytes derived from patient iPSCs

Myocardial infarction (MI), also known as heart attack, is afflicting 7.6 million Americans and cost more than 11.5 billion every year in the United States. In spite of current optimal clinical therapies, postinfraction heart failure and malignant arrhythmias remain therapeutic challenges because the limited regenerative potential of the cardiomyocytes. Stem cells therapy is supposed to be a promising treatment to fully restore the functions of myocardium after MI. Current obstacles include: cell source selection, cell survival and maturity, anisotropic structure and alignment of cardiomyocytes, electro-mechanical integration of transplanted cells with the native myocardium, and angiogenesis of neonatal cardiac tissue. In our group, we have working on fabrication of polydiolcitrates scaffold for various tissue regeneration. The polydiolcitrates are appealing because of their biocompatibility, hemocompatibility, anti-oxidant and tunable mechanical properties. Recently, we have developed strategies to make conductive film and micropatterned structures using polydiolcitrates. Meanwhile, we were able to differentiate the induced pluripotent stem cells (iPSCs) from cardiovascular disease (CAD) patient to mature cardiomyocytes. With these motivations, the overall goal of this study is to develop a novel cardiac patch with tunable mechanical and electrical properties, as well as specific topographies to regenerate functional cardiac tissue using patient specific iPSC-derived cardiomyocytes (iPSC-CMs) to restore the function of myocardium following MI. Specifically, we will: a) fabricate and characterize in vitro the multifunctional cardiac patches with patient specific iPSC-CMs, and b) assess the in vivo performance of the treatment on myocardium regeneration in a nude mouse model. We expect the combination of our multifunctional cardiac patch with patient specific iPSC-CMs will improve the cardiac regeneration compared to treat the remit the arrhythmias after MI.