Development of a 3D-printed anisotropic heart-on-a-chip for drug screening applications

Engineered ex vivo cardiac tissues have garnered increasing attention in the context of cardiovascular drug development. They offer great promise as first-line tools that can complement or even be used as proxies for some of the drug evaluations carried out with animals. However, it remains an ongoing challenge to develop 3D engineered ex vivo cardiac muscle models that more closely recapitulate native cardiac tissue. This tissue consists of an anisotropic multilayer structure, which plays a key role in regulating the unique biomechanical behaviour of the heart. In contrast, most of the current heart-on-a-chip models employ a single cardiac cell layer on a 2D flat substrate. In this project (HEARTCHIP), we propose to develop a 3D printed anisotropic heart-on-a-chip as an ex vivo acute hypoxia model for CVD drug screening. We will prepare a remote magnetic conductive bioink based on magnetic-control of short nanofiber yarns and photocurable hydrogels to induce the organization and differentiation of hiPSC-derived cardiomyocytes. We will then use a gel-in-gel 3D bioprinting approach to fabricate a 3D anisotropic, multi-layered cardiac muscle tissue. In addition, to provide automated control of culture conditions and real-time measurement of cell physiological responses, we intend to integrate the as-fabricated tissue into a microfluidic chip. With this heart-on-a-chip, we aim to perform high-throughput drug tests in the condition of acute hypoxia. Hence, this project aims to provide a new platform of cardiac tissue for rapid, high-throughput drug screening with automated control and real-time analysis.