Gel-Amin for improving signal propagation and extracellular recordings of cardiomyocytes in a 3D Microphysiological System

Abstract

Microphysiological systems (MPSs) hold great potential for fundamental discovery and accelerating the drug discovery pipeline through simplifying complex tissues to their first principles and enabling real-time, high-resolution monitoring. Hydrophilic biomaterials, such as hydrogels, are important for MPS innovations due to their ability to emulate the native extracellular matrix and tunable mechanical properties. Furthermore, hydrogels can be tailored to improve tissue maturity as well as the efficacy of instrumentation. However, many biopolymers are non-conductive, presenting complications for modeling excitable tissue environments like the heart. In this work, we show that an 8% (w/v) Gelatin Methacryloyl (GelMA) + 3.5% (v/v) Choline Acrylate hydrogel, nicknamed Gel-Amin, can amplify extracellular voltage recordings from a culture of cardiomyocytes (CMs) from commercial microelectrode arrays. Our laser cut and assemble method for manufacturing 3D MPSs allowed direct comparisons of CM signal propagation in Gel-Amin compared to control GelMA cultures in a single system. This innovative material supported in vitro CM cultures with improved synchronicity and greater signal-to-noise ratios (SNRs), suggesting potential improvements over conventional biomaterial limitations. Here, we developed a cost-effective in vitro cardiac tissue model that allows real-time electrical activity monitoring.