3D Bioprinting-based Tissue Assembly to Generate Multi-axially Contracting Engineered Heart Tissue

Abstract

Various types (e.g., strip, ring, and chamber-like) of tissue have been developed for the in vitro study of the human heart. The strip and ring types of EHT could reproduce contractility and electrophysiology of heart, however, these models have limited in pump-like cardiac functions due to the lack of structural complexity. The advancement of biofabrication enabled the generation of chamber-like models that reproduce volume-pressure dynamics. However, the level is still poor and needs improvement. In this study, we suggest a 3D bioprinting-based tissue assembly as a strategy to achieve myocardial fiber orientation, a critical architectural feature of a cardiac chamber for maximizing the chamber contraction. Tissue assembly is a method that creates larger or more complex constructs based on functional tissue units. The strip EHT was generated and functional validations regarding contractility and electrophysiology and drug responsiveness. Then the pin-hole-based assembly platform was developed to perform tissue assembly, and the assembly process was established. Based on the assembly platform, the EHTs were assembled, and assembled EHT exhibited synchronized contractile and electrophysiological functions. Simultaneously, the 3D bioprinting-based tissue assembly proved to be capable of controlling fiber orientation. Subsequently, strip and ring types of EHT, showing longitudinal and radial contraction, respectively, were generated. Then, two types of EHTs were assembled to generate multi-axially contracting EHT. In conclusion, we proposed a 3D bioprinting-based tissue assembly as a method of fabricating complex contractile tissue, which will further be advanced to build a cardiac chamber having myocardial fiber orientation.