2, The Ohio State University, Columbus, Ohio, United States
3, The Ohio State University, Columbus, Ohio, United States
Electroactive scaffolds have been intensively explored in cardiac tissue engineering, based on observations that the conductive components can enhance the ultrastructure and function of the tissue constructs. A prevalent hypothesis states that cardiac cells can be electrically bridged by conductive materials to achieve synchronization of cardiac action potentials. Thus, high conductivity is pursued as a property of priority in designing electroactive scaffolds. However, rational design of these scaffolds would be impossible without validating this hypothesis and revealing the underlying mechanism. In the current work, using equivalent circuit models, systems of cardiomyocytes-on-substrate and cardiomyocytes-via-nanowire are theoretically studied. Specifically, when one group of cells fires an action potential (AP) that is transmitted through the conductive material, the depolarizing effect on its adjacent cells is investigated. For the cardiomyocytes-on-substrate system, simulation results show that the seal resistance is the most sensitive factor to AP-induced depolarization of neighboring cells, while surface roughness and conductivity of the material have less impacts. For the cardiomyocytes-via-nanowire system, the required seal resistance for substantial depolarization is at least 1013 Ω/sqr because of the small interfacial area and large interfacial impedance. These analyses validate the electro-bridge hypothesis by confirming the positive role of conductive scaffolds and nanostructures in aiding seeded cardiac cells to electrically synchronize with each other, while revealing the cell-scaffold adhesion strength as a crucial factor to the performance. Although further experimental tests are needed to verify these analytical results, this work provides a theoretical basis to the rational design of electroactive scaffolds for enhanced cardiac tissue engineering.