Hydrogel microfluidic-based liver-on-a-chip: Mimicking the mass transfer and structural features of liver

Liver is fed by nutrition via diffusion across the vascular wall from blood flow. However, hepatocytes in liver models are directly exposed to the perfusion culture medium, where the shear stress reduces the cell viability and liver-specific functions. By mimicking the mass transfer and structural features of hepatic lobule, we designed a microfluidic liver-on-a-chip based on the di-acrylated pluronic F127 hydrogel. In the hydrogel chip, hepatocellular carcinoma HepG2 and human hepatic stellate cell LX-2 were statically cultured inside the microwells on the outer channel. These hepatic cells were fed by the diffused medium from the adjacent but separated inner channel with endothelial cell monolayers, which was perfused by the medium with physiologically relevant shear stress. As found, the hepatic cells in the liver-on-a-chip rapidly formed spheroids within 1-day incubation and expressed about one to two-fold higher viability/liver-specific functions than the corresponding static culture for at least 8 days. Moreover, the presence of endothelial cells also contributed to the expression of liver-specific functions in the liver-on-a-chip. Therefore, the proposed liver-on-a-chip provides a new concept for construction of 3D liver models in vitro, and shows the potential value for a variety of applications including bio-artificial livers and drug toxicity screening.