Abstract 11979: Direct Assessment of Engineered Heart Tissue Field Potential and Contraction Dynamics Using Flexible Electronics Technology

Abstract

Introduction: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) enable the study of human heart disease in a dish. However, when cultured as cells on plastic, these 2D models are immature and exhibit non-physiologic outputs. When cultured as engineered heart tissues (EHTs or 3D models), hiPSC-CMs display a more mature gene and protein profile. Although multielectrode array (MEA) platforms have been applied to 2D cultures to study the electrical properties of hiPSC-CMs, a similar approach has been lacking for EHTs. We now took advantage of technological advances in flexible electronics to create a 3D platform that allows continuous transduction of field potential and strain of human EHTs. Methods and Results: Using microfabrication techniques adapted from the semiconductor industry, custom ring-shaped flexible electronics constructs were created with 6 support posts. Each post included a microelectrode for recording electrophysiological information and a piezoresistive strain sensor for monitoring EHT contraction dynamics. These were integrated onto a flexible biocompatible polyimide support. hiPSCs were differentiated into hiPSC-CMs, and EHTs were generated by seeding 500,000 cells composed of 90% hiPSC-CMs and 10% human cardiac fibroblasts into a collagen matrix and deposited in the ring-shaped polydimethylsiloxane (PDMS) molds. Tissues were condensed over 7 days and then were transferred onto the flexible electronic scaffolds. Tissues remodeled for ~30 days and then were analyzed for contractile properties. Direct tissue stimulation and field potential measurements were obtained in real time using an Intan RHS stimulation recording system. Simultaneous recording of force of contraction relied on a calibrated Wheatstone bridge circuit. EHTs from hiPSC-CMs displayed appropriate contractile responses to pharmacologic agents. Conclusion: Although EHTs improve hiPSC-CM models by improving cellular maturity, it has been challenging to measure physiological outcomes. We now developed a prototype that simultaneously provides electrophysiologic and contractility characterization in real time of human EHTs.