Microneedle array facilitates hepatic sinusoid construction in a large-scale liver-acinus-chip microsystem

Area of Science:

• Biotechnology
• Tissue Engineering
• Microfluidics

Background:

• Hepatic sinusoids are crucial for liver cell function within the hepatic acinus.
• Constructing functional hepatic sinusoids remains a significant challenge for liver-on-a-chip technologies, particularly in large-scale applications.

Purpose of the Study:

• To develop a novel approach for fabricating hepatic sinusoids in large-scale liver-on-a-chip microsystems.
• To investigate the impact of engineered sinusoids on liver cell viability, microstructure, and metabolic functions.

Main Methods:

• Utilized a self-developed microneedle array for demolding a photocurable, cell-loaded matrix.
• Engineered a large-scale liver-acinus-chip microsystem with a dual blood supply.
• Observed primary sinusoids formed by demolding and secondary sinusoids that self-organized spontaneously.

Main Results:

• Successfully formed primary and secondary hepatic sinusoids within the liver chip.
• Demonstrated significantly enhanced interstitial flows, leading to high cell viability and improved liver microstructure.
• Observed enhanced hepatocyte metabolism and preliminary insights into oxygen/glucose gradients affecting liver function.

Conclusions:

• The developed microneedle array demolding technique enables the biofabrication of functional hepatic sinusoids in large-scale liver systems.
• Engineered sinusoids improve liver chip performance, supporting cell viability, microstructure, and metabolic activity.
• This approach holds promise for creating advanced, fully functionalized large-scale liver bioreactors for research and drug testing.