4D Printed Cardiac Construct with Aligned Myofibers and Adjustable Curvature for Myocardial Regeneration.

As an innovative additive manufacturing process, 4D printing can be utilized to generate predesigned, self-assembly structures which can actuate time-dependent, and dynamic shape-changes. Compared to other manufacturing techniques used for tissue engineering purposes, 4D printing has the advantage of being able to fabricate reprogrammable dynamic tissue constructs that can promote uniform cellular growth and distribution. For this study, a digital light processing (DLP)-based printing technique was developed to fabricate 4D near-infrared (NIR) light-sensitive cardiac constructs with highly aligned microstructure and adjustable curvature. As the curvature of the heart is varied across its surface, the 4D cardiac constructs can change their shape on-demand to mimic and recreate the curved topology of myocardial tissue for seamless integration. To mimic the aligned structure of the human myocardium and to achieve the 4D shape change, a NIR light-sensitive 4D ink material, consisting of a shape memory polymer and graphene, was created to fabricate microgroove arrays with different widths. The results of our study illustrate that our innovative NIR-responsive 4D constructs exhibit the capacity to actuate a dynamic and remotely controllable spatiotemporal transformation. Furthermore, the optimal microgroove width was discovered via culturing human induced pluripotent stem cell-derived cardiomyocytes and mesenchymal stem cells onto the constructs' surface and analyzing both their cellular morphology and alignment. The cell proliferation profiles and differentiation of tricultured human-induced pluripotent stem cell-derived cardiomyocytes, mesenchymal stem cells, and endothelial cells, on the printed constructs, were also studied using a Cell Counting Kit-8 and immunostaining. Our results demonstrate a uniform distribution of aligned cells and excellent myocardial maturation on our 4D curved cardiac constructs. This study not only provides an efficient method for manufacturing curved tissue architectures with uniform cell distributions, but also extends the potential applications of 4D printing for tissue regeneration.

Advanced 4D Bioprinting Technologies for Brain Tissue Modeling and Study.

Although the process by which the cortical tissues of the brain fold has been the subject of considerable study and debate over the past few decades, a single mechanistic description of the phenomenon has yet to be fully accepted. Rather, two competing explanations of cortical folding have arisen in recent years; known as the axonal tension and the differential tangential expansion models. In the present review, these two models are introduced by analyzing the computational, theoretical, materials-based, and cell studies which have yielded them. Then Four-dimensional bioprinting is presented as a powerful technology which can not only be used to test both models of cortical folding de novo, but can also be used to explore the reciprocal effects that folding associated mechanical stresses may have on neural development. Therein, the fabrication of "smart" tissue models which can accurately simulate the in vivo folding process and recapitulate physiologically relevant stresses are introduced. We also provide a general description of both cortical neurobiology as well as the cellular basis of cortical folding. Our discussion also entails an overview of both 3D and 4D bioprinting technologies, as well as a brief commentary on recent advancements in printed central nervous system tissue engineering.