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Updated: Mar 27, 2026
"Liver-on-a-Chip" Cultures of Primary Hepatocytes and Kupffer Cells for Hepatitis B Virus Infection
Published on: February 19, 2019
A liver-on-a-chip platform with bioprinted hepatic spheroids
Nupura S Bhise1, Vijayan Manoharan, Solange Massa
1Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
This study developed a liver-on-a-chip platform using 3D human liver spheroids for accurate drug toxicity testing. The model successfully predicted acetaminophen toxicity, offering a promising alternative to animal testing.
Area of Science:
- Biomedical Engineering
- Toxicology
- Hepatology
Background:
- Current animal models inadequately predict human drug and biothreat agent toxicity.
- The liver is a critical organ for assessing drug-induced toxicity.
- There is a need for advanced in vitro models that mimic in vivo conditions.
Purpose of the Study:
- To develop a novel liver-on-a-chip platform for long-term culture of 3D human liver spheroids.
- To enable in situ monitoring and bioprinting for advanced hepatic construct fabrication.
- To assess the platform's utility for drug toxicity evaluation.
Main Methods:
- Fabrication of a bioreactor for long-term culture of 3D HepG2/C3A spheroids.
- Integration with a bioprinter for encapsulating spheroids in gelatin methacryloyl (GelMA) hydrogel.
- Monitoring of hepatic function markers (albumin, AAT, transferrin, ceruloplasmin) and hepatocyte markers via immunostaining over 30 days.
Main Results:
- The liver-on-a-chip platform supported functional 3D human liver spheroids for 30 days.
- Confirmed hepatic function through sustained secretion of key proteins and expression of hepatocyte markers.
- Acetaminophen treatment (15 mM) induced a toxic response consistent with existing models, validating the platform's predictive capability.
Conclusions:
- The developed liver-on-a-chip platform provides a functional and long-term in vitro model for drug toxicity assessment.
- This platform offers a promising alternative to animal testing, improving the accuracy of predicting human responses to drugs and biothreat agents.
