3D printing of thick myocardial tissue constructs with anisotropic myofibers and perfusable vascular channels

Engineering of myocardial tissues has become a promising therapeutic strategy for treating myocardial infarction (MI). However, a significant challenge remains in generating clinically relevant myocardial tissues that possess native microstructural characteristics and fulfill the requirements for implantation within the human body. In this study, a thick 3D myocardial construct with anisotropic myofibers and perfusable branched vascular channels is created with clinically relevant dimensions using a customized beam-scanning stereolithography printing technique. To obtain tissue-specific matrix niches, a decellularized extracellular matrix microfiberreinforced gelatin-based bioink is developed. The bioink plays a crucial role in facilitating the precise manufacturing of a hierarchical microstructure, enabling us to better replicate the physiological characteristics of the native myocardial tissue matrix in terms of structure, biomechanics, and bioactivity. Through the integration of the tailored bioink with our printing method, we demonstrate a biomimetic architecture, appropriate biomechanical properties, vascularization, and improved functionality of induced pluripotent stem cell-derived cardiomyocytes in the thick tissue construct in vitro. This work not only offers a novel and effective means to generate biomimetic heart tissue in vitro for the treatment of MI, but also introduces a potential methodology for creating clinically relevant tissue products to aid in other complex tissue/organ regeneration and disease model applications.