Modular Assembly of 3D Bioprinted Engineered Heart Tissue to Reconstruct Contractile Direction to Mimic Myocardial Fiber Orientation

An engineered heart tissue (EHT) derived from human induced pluripotent stem cells (hiPSCs) allows to study of human cardiac pathophysiology. Various types of EHT such as spheroid, strip, and ring have been reported to exhibit contractility and electrophysiological properties of the native heart. However, the limited geometric complexity of these models remains a challenge to achieve other cardiac functions including volume-pressure handling and pump fluid. In this study, we propose a strategy to achieve the myocardial fiber orientation using 3D bioprinting-based modular tissue engineering. The myocardial fiber orientation, which is associated with efficient systolic function, is a unique structural feature of the heart. We employed 3D bioprinting for rapid prototyping of EHT modules in various shapes and sizes. The developed EHT module was confirmed to reproduce cardiac-specific functions such as contractility, electrophysiological properties and drug responsiveness. Furthermore, the EHT modules were assembled to reconstruct contractile direcrtion to mimic native myocardial fiber orientation. These findings will be applied to fabricate chamber-like construct that contains myocardial fiber orientation.1