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Advanced liver-on-chip model mimicking hepatic lobule with continuous microvascular network via high-definition laser
Masafumi Watanabe1,2,3, Alice Salvadori1,2, Marica Markovic1,2
1Research Group 3D Printing and Biofabrication, Institute of Materials Science and Technology, Technische Universität Wien (TU Wien), 1060 Vienna, Austria.
Materials Today. Bio
|April 10, 2025
Summary
This study presents an advanced liver-on-chip model that accurately mimics the hepatic lobule and its microvasculature using femtosecond laser patterning. This novel biomimetic model demonstrates key liver functions and drug toxicity, advancing preclinical drug development.
Area of Science:
- Biomedical Engineering
- Regenerative Medicine
- Drug Development
Background:
- Accurate preclinical drug efficacy and safety prediction requires advanced in vitro liver models.
- Mimicking the complex hepatic lobule structure with a continuous microvascular network remains a significant challenge.
- Femtosecond laser patterning offers high-resolution fabrication of biomimetic structures.
Purpose of the Study:
- To develop an advanced liver-on-chip model that precisely replicates the hepatic lobule's architecture, including a continuous microvascular network.
- To utilize femtosecond laser patterning for creating biomimetic microchannels within a hydrogel matrix.
- To validate the model's physiological relevance and utility in predicting drug-induced hepatotoxicity.
Main Methods:
- Femtosecond laser patterning was optimized to create microchannels mimicking hepatic microvessels and the central vein within a collagen-based hydrogel containing hepatic cells.
- Continuous microvessels with luminal structures were constructed by systematically varying microchannel diameters.
- A multi-layered, millimeter-scale hepatic lobule-like structure with integrated microvascular networks was assembled on-chip.
Main Results:
- The optimized laser patterning successfully created biomimetic microchannels replicating the liver's microvasculature.
- Continuous microvascular networks with defined luminal structures were established, forming a functional unit.
- The liver-on-chip model exhibited key liver functions, including albumin and urea production, and responded to acetaminophen exposure, indicating hepatotoxicity.
Conclusions:
- This study successfully developed a novel liver-on-chip model mimicking the hepatic lobule using femtosecond laser patterning.
- The model demonstrates physiological functions and predicts drug-induced toxicity, offering a valuable tool for pharmaceutical and toxicological research.
- This approach provides advanced strategies for creating sophisticated in vitro liver models for preclinical drug development.
