Real-time and Multichannel Measurement of Contractility of hiPSC-Derived 3D Skeletal Muscle using Fiber Optics-Based Sensing

Abstract

As the field of cardiac and skeletal muscle tissue engineering expands, so does the need for accurate and reliable systems to generate in vitro 3D tissues and analyze their functional properties. In this study, the Cuore is introduced, a system that integrates sensors based on optical fibers and uses the principle of light interferometry to detect the contraction of 3D Tissue Engineered Skeletal Muscles (3D-TESMs). The technology employed in the Cuore allows for reproducible and multichannel force measurements down to a nano-Newtons resolution while maintaining sterility and permitting continuous non-invasive recording within and outside standard tissue culture incubators. Thanks to the integrated electrodes for electrical pulse stimulation (EPS), 3D-TESMs generated from three independent hiPSC-derived myogenic progenitors (MPs) lines are stimulated and the contractility is recorded over the course of a week. Through the modulation of different EPS parameters, the optimal combination to induce the 3D-TESMs in producing fully fused tetani without causing damage is determined. Furthermore, 3D-TESMs from different lines exhibit characteristic signatures of spontaneous contractility and response to caffeine, verapamil, and the β-agonist clenbuterol. The ease of use, high sensitivity, and the integrated electrodes and sensors make the Cuore an ideal technology to investigate the biology of contractile tissues and their response to drugs.