One-Step Laser-Assisted Electrohydrodynamic Printing of Microelectronic Scaffolds for Electrophysiological Monitoring of Aligned Cardiomyocytes.

Abstract

Micro/nanoscale bioelectronics show great promise to noninvasively monitor the electrophysiological activities of electroactive tissue constructs. However, the existing methods to incorporate microelectronics into biological scaffolds commonly rely on multiple microfabrication and manual assembly processes, restraining the controllability of the microelectrode arrangement and similarity of cellular organizations to native tissues. Herein, a laser-assisted electrohydrodynamic (EHD) printing strategy is proposed to directly fabricate a microfibrous architecture with built-in microelectronics for electrophysiological monitoring of aligned cardiomyocytes. A dual-nozzle EHD printing system is developed to sequentially print polycaprolactone (PCL) microfibers, gold microelectrodes, and high-density parallel microfibers in a layer-by-layer manner. The microelectrodes are precisely deposited between two layers of PCL microfibers and locally sintered by laser to achieve a conductivity of 2.82 × 10⁶ S m^-1. The encapsulated microelectrodes with a predefined exposure length can be freely and reproducibly printed at the specific position inside the microfibrous architecture and exhibit good electrical stability under cell-culturing conditions, which enables noninvasive, high-quality, and spatiotemporal electrophysiological readouts of aligned cardiomyocytes directed by the top parallel microfibers. The presented technique provides an innovative strategy to directly fabricate functional electroactive tissue constructs with built-in bioelectronics for in situ electrophysiological monitoring to advance the fields of drug testing and organ-on-chip systems.