Abstract 13447: An Injectable Conductive Polymer Hydrogel Improves Electrical Conduction Velocity in the Injured Heart

Introduction: Scar formation after a myocardial infarction (MI) delays electrical impulse propagation, inducing dysynchronous cardiac activation and uncoordinated contraction. We generated an injectable biocompatible conductive polymer that not only stabilized the infarct region, but also facilitated electrical signal propagation across the scar tissue to enhance synchronous ventricular contraction. Methods/Results: Oxidative polymerization was employed to conjugate polypyrrole (PPY) to chitosan (CHI) and hydrogels were created by glutaraldehyde crosslinking. Biomaterials with 4 different PPY:CHI ratios (CHI, 3PPY:10CHI, 3 PPY:100 CHI, 3 PPY:1000CHI ) were generated. Electrical conductivity was measured by two-probe cyclic voltammetry. The 3PPY:10CHI ratio had significantly greater conductivity than the other concentrations (2.37х10-4±6.25х10-5S/cm, n=6, P<0.05). Improved electrical propagation was demonstrated when neonatal rat cardiomyocytes cultured on 3PPY:10CHI had significantly higher Ca2+ transient propagation velocity (by optical mapping with a fluo-4/AM indicator) than those cultured on other concentrations (17.25±2.23cm/s, n=15, P<0.05). Thus, 3PPY:10CHI was employed for in vivo studies employing a cryoinjury model (with a uniform scar size). Saline, CHI, and 3PPY:10CHI were injected into Sprague-Dawley rat hearts 1 week after injury. The sequence of cardiac electrical activation was visualized using an optical mapping system 1 month post-injection. Saline (57.7±2.5cm/s, n=4)- and CHI (47.1±3.5cm/s, n=3)-injected hearts showed disrupted propagation patterns and significantly reduced conduction velocity, while 3PPY:10CHI (74.3±4.7cm/s, n=5)-treated hearts had higher conduction velocities that were similar to healthy controls (81.3±0.59cm/s, n=3). Conclusion: A polypyrrole-conjugated chitosan hydrogel supported cell attachment and improved electrical conductivity in vitro. The 3PPY:10CHI biomaterial enhanced Ca2+ transient propagation in cultured cardiomyocytes and intra-myocardial injection of the material improved longitudinal electrical impulse propagation across the scar. This new biomaterial may be a new potential therapy to synchronize cardiac contraction.