Flexible beam-based microelectrode arrays integrated with oriented nanofiber scaffolds for electrophysiological monitoring of cardiac tissue.

Abstract

In vitro culture and electrophysiological monitoring of engineered cardiac tissue (ECT) are crucial for the screening and evaluation of cardiotoxic drugs. Microelectrode arrays (MEAs) offer significant advantages in non-invasive, high-throughput detection. However, existing MEAs face challenges in replicating the natural growth environment of cardiomyocytes, which hinders the morphology and functional maturation of cells. In this study, a flexible beam-based microelectrode array (BMEA) integrated with nanofiber scaffolds is presented for the culturing of well-aligned cardiac tissue and the monitoring of electrophysiological signals. Oriented nanofibers are suspended on flexible polydimethylsiloxane beams to create a 3D culture environment for tissue. The BMEA exhibits low impedance (22 ± 7 kΩ@1 kHz for electrode width of 100 μm), stable electrochemical performance, and good biocompatibility. Through a 10-day continuous culture and drug stimulation of human induced pluripotent stem cell-derived cardiomyocytes, the device demonstrates the ability to capture the electrophysiological signals dynamically while promoting the structural and functional maturation of cardiomyocytes, which show better cell orientation, larger cell size, and faster conduction velocity (∼ 21 cm/s). Further drug tests validate the effectiveness of this device. The BMEA provides a perspective tool for screening and evaluation of drug cardiotoxicity to cardiac tissues. STATEMENT OF SIGNIFICANCE: The mechanical mismatch between traditional rigid MEAs and flexible biological tissues has been partially addressed by the development of flexible MEAs based on polymer or hydrogel substrates. However, these 2D adherent culture methods still face several limitations, including lack of biomimetic ECM microstructure, insufficient intercellular interactions, and directional access to nutrients, thereby posing challenges to the growth of cardiac tissue and the maturation of its electrophysiological functions. Herein, a flexible PDMS beam-based microelectrode array (BMEA) integrated with oriented nanofiber scaffolds is proposed for in-situ electrophysiological monitoring of aligned cardiac tissue in a suspended and biomimetic 3D culture environment. The BMEA provides a promising tool for screening and evaluation of drug cardiotoxicity to cardiac tissues.