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Biomimetic hepatic lobules from three-dimensional imprinted cell sheets

Peer-Reviewed Publication

Science China Press

Biomimetic hepatic lobules from three-dimensional imprinted cell sheets

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Inspired by hepatic lobules, a novel artificial liver was developed by assembling morphological cell sheets with high accuracy in terms of cell type, density, and distribution. By simulating the spatial niche of liver cells, the liver cell sheets were stacked and printed in a spatial manner to construct hollow hexagonal prism-shaped liver microunits. After introducing endothelial cells, bioengineered liver lobules with vascularized channels were obtained and could be used for drug screening in liver chips. Furthermore, by assembling the vascularized bioengineered liver lobules into enlarged physiological structures, they can enhance the liver's regenerative capacity. This printing and assembly strategy of cell sheets mimicking liver lobule structures opens up new pathways for bioengineered liver development.

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Credit: ©Science China Press

This study is led by Prof. Yuanjin Zhao (Department of Hepatobiliary Surgery, Hepatobiliary Institute, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing 210008, China).

To establish high-precision liver lobules, researchers utilized spatial proteogenomic datasets to identify the multicellular specific composition in the normal human liver. Based on this data and cell membrane slicing technology, researchers then employed a newly developed 3D printing strategy to print and carve liver cell sheets with hexagonal hollow cross-sectional structures.

Through various self-assembly methods, researchers achieved the stacking of multiple layers of lobules, integrating multiple lobule structures to mimic the microscale units of the liver. Furthermore, by infiltrating endothelial cells into the hollow cross-sections of the assembled lobule structures, researchers obtained bioengineered liver lobules with vascularized channels for nutrient diffusion and drug perfusion.

Additionally, by integrating these vascularized bioengineered liver lobules with microfluidics, researchers constructed liver chips and validated their application in drug screening. Finally, researchers further assembled the vascularized bioengineered liver lobules to form larger physiological structures and demonstrated their ability to promote liver regeneration by in situ transplantation into livers of rats with acute liver failure.

See the article:

Jinglin Wang, Danqing Huang, Hanxu Chen, Yuanjin Zhao. Biomimetic hepatic lobules from three-dimensional imprinted cell sheets. Science Bulletin 2024; doi: 10.1016/j.scib.2024.02.030

https://www.sciencedirect.com/science/article/pii/S2095927324001324


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