Artificial liver lobule! Opening up new path for bionic liver!

Recently, researchers have provided a novel three-dimensional imprinted cell sheet assembly strategy for the synchronous construction of bionic liver lobules with high accuracy in cell type, density and distribution.

Strategies for assembling 3D imprinted cell sheets

Background

Bioengineered liver tissue has certain prospects in the treatment of liver diseases. Generally speaking, the human liver is composed of tiny radially shaped hepatic lobules combined with vascular and biliary networks. In order to simulate the liver structure, many strategies have been developed to manufacture three-dimensional bionic liver models. According to the current reports, researchers can arrange human parenchymal cells, stromal cells and even vascular cells into a specific grid structure by applying geometric graphics of material cues, simulating interstitial microstructures, and realizing cell distribution and some liver functions.

With the development of micro-nanotechnology in recent years, bioprinting and other tissue engineering technologies can construct biological tissues with three-dimensional structures, and further realize the bionics and construction of vascular networks and microcirculatory systems. Although current technologies have achieved many successes in the bionic construction of livers, most of the current research has only achieved a simple imitation of the geometric structure of the liver, and it is difficult to construct a high-density composition of cell stacking and multi-cellular structure interaction, resulting in unsatisfactory liver tissue engineering results. Therefore, achieving the synchronous construction of cell types, density and distribution is still an important direction of bionic liver biological tissue engineering research.

Research highlights

To establish a high-precision liver lobule, the researchers used spatial proteogenomics datasets to identify the multicellular specific composition of normal human liver. Based on these data and cell membrane technology, the researchers then used a newly developed three-dimensional stamping strategy to stamp and carve out a hexagonal hollow cross-sectional structure of liver cell sheets from liver cell sheets.

Through different self-assembly methods, the researchers achieved multi-layer lobule superposition and integration of multiple lobule structures to simulate the microscopic units of the liver. Furthermore, by infiltrating vascular endothelial cells into the hollow cross-section of the assembled lobule structure, the researchers obtained a bionic liver lobule with vascularized channels for nutrient diffusion and drug perfusion.

By integrating these vascularized bionic liver lobules with microfluidics, the researchers constructed a liver chip and verified its application in drug screening. Finally, the researchers further assembled the vascularized bionic liver lobules into a larger physiological structure and demonstrated its ability to promote liver regeneration by in situ transplantation into rats with liver failure.

In summary, this new type of bionic liver lobule provides a construction method with great potential for liver tissue engineering. The relevant research article was recently published in Science Bulletin.

For more details, please read the original 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