Flexible electronic substrates to deliver electromechanical stimuli to regenerative cardiac patches

Abstract

After myocardial infarction, the stressed environment may cause negative cardiac remodeling. An emerging treatment option, engineered cardiac patches can be mechanically conditioned to increase alignment or electrically stimulated to enable anisotropic conduction. While proper integration with native tissue may require both stimuli, very few studies have applied both simultaneously, and only to extracted tissues. To demonstrate feasibility, a rigid electrode prototype was constructed to incorporate electrical stimulation into a commercially available mechanical conditioning system. Electrodes were assembled to fit the system’s geometry, and parameters were optimized to mimic the human heart rate. Previously, a study used 5-Azacytidine (5-Aza) to differentiate mesenchymal stem cells (MSCs) toward cardiac lineage, which was used here for proof-of-concept testing. Unexpectedly, MSCs treated with 5-Aza and electrically stimulated showed a decrease in cardiac marker troponin and an increase in MSC surface marker gene expression. In this setup, current from rigid electrodes passes through the media; however, under physiologically relevant conditions, electrical signals should propagate directly through cardiomyocytes. Therefore, a method to apply electromechanical stimulation to individual cells was explored in a point source stimulation platform. Electroconductive adhesive (ECA), a composite of silver and polydimethylsiloxane, was used to fabricate flexible elastic microelectrode arrays that provided positive and negative voltage sources to individual cells. Devices were not cytotoxic before applying an electric field; however, applied current caused electrolysis of media and cytotoxicity, even using current stimulation parameters lower than those in published studies. These findings suggest ECA electrochemical properties need more characterization and alternative materials for microelectrodes.