PEDOT: PSS-Modified Organic Flexible and Implantable Microelectrode for Internal Bi-Directional Electrophysiology of Three-Dimensional Cardiomyocyte Spheroid.

Three-dimensional (3D) cardiomyocyte spheroids are essential models to replicate cardiac structural and functional features in vitro. However, conventional planar and rigid microelectrode arrays (MEAs) suffer from low-quality electrophysiological recording of 3D cultures, due to limited contact areas and weak coupling between cells and MEA chips. Herein, we developed a PEDOT: PSS-modified organic flexible and implantable MEA (OFI-MEA) coupled with a self-developed integrated biosensing platform to achieve high-throughput, long-term, and stable bidirectional internal electrophysiology in 3D cardiomyocyte spheroids. Electrostimulation enhanced the functional performance of the 3D cardiomyocytes, causing a remarkable 2.69-fold increase in frequency. Furthermore, time-frequency analysis of the multisite electrophysiological signals to highlight diverse cell activity patterns in the spheroids. It provides a powerful tool to record electrophysiological signals of 3D cardiomyocyte spheroids, allowing continuing evaluation of cardiac dynamics and regulation of electrical signals, providing a novel evaluation strategy for cardiac disease model construction, drug screening, and cardiological research.