Fabrication of Conductive Polymer-Conjugated Citrate-Based Elastic Cardiac Patch

<b>Introduction: </b>Myocardial infarction (MI), also known as heart attack, afflicts 790,000 Americans and leads to 114,000 deaths every year.¹ In spite of current optimal clinical therapies, post-infarction heart failure and malignant arrhythmias remain challenges because of the limited regenerative potential of cardiomyocytes. Novel engineered systems such as cardiac patches have the potential to overcome these problems. The cardiac patch as a scaffold to support and deliver stem cells and cardiomyocytes can improve cell survival and integration with native tissue.² In this study, we developed a novel cardiac patch with tunable mechanical and electrical properties for regeneration of functional cardiac tissue using poly(1,8 octamethylene citrate) (POC).<br/><b>Materials and Methods:</b> Conductive POC patches were prepared in two steps. The first step was to fabricate the POC elastic cardiac patch by curing POC pre-polymer at 70 °C for 4 days. The POC film was put into PBS buffer to remove uncured pre-polymer. Then, a conductive polyaniline (PA) layer was deposited onto the POC film via <i>in situ</i> polymerization. Tensile strength of the patches was measured using an Instron tensile tester (5944). The surface properties were characterized using a FEI Quanta 650 scanning electron microscope (SEM) and an Atomic Force Microscope (AFM). Conductivity of the patches was tested using a four-probe method via Agilent 4155C. Surface chemical properties were characterized using a Thermo Scientific ESCALAB 250 Xi X-ray photoelectron spectroscopy (XPS) and Fourier-transform infrared spectroscopy (FTIR). Electromyography (EMG) was recorded with 10V stimulation. Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) were cultured on the patches for <i>in vitro</i> function analysis. The cardiac patches were implanted in Sprague Dawley rats to treat acute myocardial infarction (MI).<br/><b>Results and Discussion:</b> The fabricated POC cardiac patch has a tensile modulus of 0.2 MPa that is comparable to the reported mechanical properties of native myocardium. A conductive PA layer was successfully deposited onto the POC film according to the XPS and FTIR results. The conductivity (10^-3 S/cm) and electrical signal propagation were enhanced due to the PA layer. Interestingly, via in situ polymerization, PA was conjugated onto POC surface which enhanced the physical stability of deposited layer. Additionally, due to the intrinsic polyanion structure of POC, the conjugated PA layer showed enhanced electrical stability under physiological conditions. Various PA micropatterns were further fabricated for cardiac function monitoring. The electro-mechanical integrated cardiac patch promoted synchronization of iPSC-CMs beating <i>in vitro</i>, preserved cardiac functions, and reduced scar formation <i>in vivo</i>.<br/><b>Conclusions: </b>A novel cardiac patch with electrical, mechanical, and biocompatibility properties that are suitable for use on the heart was fabricated. The properties of the POC patches were conducive to minimizing the damage caused by an infarct to cardiac tissue.<br/><b>Acknowledgements: </b>This work was supported by the Center for Advanced Regenerative Engineering (CARE), Northwestern University, American Heart Association (AHA) (Award No: 19POST34400088), and the National Science Foundation (NSF) Emerging Frontiers in Research and Innovation (EFRI) (Award No: 1830968).<br/><b>References: </b><br/>1. Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, et al. <i>Circulation</i>, 2017, <i>135</i>, e146-e603.<br/>2. Xinlong W, Nancy RB, Bin J, Guillermo A. <i>Adv. Funct. Mater.</i> 2019, 1809009.