基于压印细胞片组装的仿生肝小叶

Liver-tissue engineering has proven valuable in treating liver diseases,but the construction of liver tissues with high fidelity remains challenging.Here,we present a novel three-dimensional(3D)-imprinted cell-sheet strategy for the synchronous construction of biomimetic hepatic microtissues with high accuracy in terms of cell type,density,and distribution.To achieve this,the specific composition of hepatic cells in a normal human liver was determined using a spatial proteogenomics dataset.The data and biomimetic hepatic micro-tissues with hexagonal hollow cross-sections indicate that cell information was successfully generated using a homemade 3D-imprinted device for layer-by-layer imprinting and assembling the hepatic cell sheets.By infiltrating vascular endothelial cells into the hollow section of the assembly,biomimetic hepatic microtissues with vascularized channels for nutrient diffusion and drug perfusion can be obtained.We demonstrate that the resultant vascularized biomimetic hepatic micro-tissues can not only be integrated into a microfluidic drug-screening liver-on-a-chip but also assembled into an enlarged physiological structure to promote liver regeneration.We believe that our 3D-imprinted cell sheets strategy will open new avenues for biomimetic microtissue construction.

Engineered 3D liver-tissue model with minispheroids formed by a bioprinting process supported with in situ electrical stimulation

Three-dimensional(3D)bioprinting,an effective technique for building cell-laden structures providing native extracellular matrix environments,presents challenges,including inadequate cellular interactions.To address these issues,cell spheroids offer a promising solution for improving their biological functions.Particularly,minispheroids with 50-100μm diameters exhibit enhanced cellular maturation.We propose a one-step minispheroid-forming bioprinting process incorporating electrical stimulation(E-MS-printing).By stimulating the cells,minispheroids with controlled diameters were generated by manipulating the bioink viscosity and stimulation intensity.To validate its feasibility,E-MS-printing process was applied to fabricate an engineered liver model designed to mimic the hepatic lobule unit.E-MS-printing was employed to print the hepatocyte region,followed by bioprinting the central vein using a core-shell nozzle.The resulting constructs displayed native liver-mimetic structures containing minispheroids,which facilitated improved hepatic cell maturation,functional attributes,and vessel formation.Our results demonstrate a new potential 3D liver model that can replicate native liver tissues.