Bioprinting‐assisted Tissue Assembly for Structural and Functional Modulation of Engineered Heart Tissue Mimicking Left Ventricular Myocardial Fiber Orientation

Abstract

Left ventricular twist is influenced by the unique oriented structure of myocardial fibers. Replicating this intricate structural-functional relationship in an in vitro heart model remains challenging, mainly due to the difficulties in achieving a complex structure with synchrony between layers. This study introduces a novel approach through the utilization of bioprinting-assisted tissue assembly (BATA)-a synergistic integration of bioprinting and tissue assembly strategies. By flexibly manufacturing tissue modules and assembly platforms, BATA can create structures that traditional methods find difficult to achieve. This approach integrates engineered heart tissue (EHT) modules, each with intrinsic functional and structural characteristics, into a layered, multi-oriented tissue in a controlled manner. EHTs assembled in different orientations exhibit various contractile forces and electrical signal patterns. The BATA is capable of constructing complex myocardial fiber orientations within a chamber-like structure (MoCha). MoCha replicates the native cardiac architecture by exhibiting three layers and three alignment directions, and it reproduces the left ventricular twist by exhibiting synchronized contraction between layers and mimicking the native cardiac architecture. The potential of BATA extends to engineering tissues capable of constructing and functioning as complete organs on a large scale. This advancement holds the promise of realizing future organ-on-demand technology.

Bioprinting-assisted tissue assembly, a hierarchical additive manufacturing process, enables the construction of intricate structures. This approach facilitates directional modulation of the structure and functions of uniaxial living tissues. In addition, it induces tissue integration, allowing several building blocks to function as single tissues. Consequently, this work generates a chamber-like tissue mimicking the myocardial fiber orientation and twisting function. image