Bioprinted 3D vascularized tissue model for drug toxicity analysis

To develop biomimetic three-dimensional (3D) tissue constructs for drug screening and biological studies, engineered blood vessels should be integrated into the constructs to mimic the drug administration process in vivo. The development of perfusable vascularized 3D tissue constructs for studying the drug administration process through an engineered endothelial layer remains an area of intensive research. Here, we report the development of a simple 3D vascularized liver tissue model to study drug toxicity through the incorporation of an engineered endothelial layer. Using a sacrificial bioprinting technique, a hollow microchannel was successfully fabricated in the 3D liver tissue construct created with HepG2/C3A cells encapsulated in a gelatin methacryloyl hydrogel. After seeding human umbilical vein endothelial cells (HUVECs) into the microchannel, we obtained a vascularized tissue construct containing a uniformly coated HUVEC layer within the hollow microchannel. The inclusion of the HUVEC layer into the scaffold resulted in delayed permeability of biomolecules into the 3D liver construct. In addition, the vascularized construct containing the HUVEC layer showed an increased viability of the HepG2/C3A cells within the 3D scaffold compared to that of the 3D liver constructs without the HUVEC layer, demonstrating a protective role of the introduced endothelial cell layer. The 3D vascularized liver model presented in this study is anticipated to provide a better and more accurate in vitro liver model system for future drug toxicity testing.