Cell-printed 3D liver-on-a-chip possessing a liver microenvironment and biliary system

Area of Science:

• Biomedical Engineering
• Drug Discovery
• Regenerative Medicine

Background:

• Current in vitro liver models face limitations including labor intensity and lack of essential components like extracellular matrix (ECM) and a biliary system.
• Existing liver-on-a-chip technologies often fail to replicate the complex microenvironment and physiological functions of the native liver, hindering accurate drug toxicity and efficacy assessments.
• The absence of a functional biliary system in current models prevents the excretion of toxic bile acids, impacting hepatocyte health and model reliability.

Purpose of the Study:

• To develop an advanced 3D liver-on-a-chip model overcoming limitations of existing technologies.
• To incorporate a decellularized extracellular matrix (ECM) bioink and a functional biliary system into the liver-on-a-chip design.
• To evaluate the enhanced functionality and drug response of the novel 3D liver-on-a-chip compared to traditional models.

Main Methods:

• Utilized cell-printing technology to fabricate a 3D liver-on-a-chip model.
• Incorporated multiple cell types, liver decellularized ECM bioink for a 3D microenvironment, and vascular/biliary fluidic channels.
• Compared liver-on-a-chip models with and without a biliary fluidic channel, and assessed 2D vs. 3D cultures.

Main Results:

• The 3D liver-on-a-chip with a biliary fluidic channel demonstrated improved biliary system formation, liver-specific gene expression, and overall liver functions.
• The developed 3D liver-on-a-chip exhibited superior functionalities compared to both 2D cultures and 3D cultures lacking a biliary system.
• Acetaminophen drug response evaluation confirmed the model's effectiveness as a drug testing platform.

Conclusions:

• The novel cell-printed 3D liver-on-a-chip effectively replicates key liver functions and microenvironmental cues.
• The inclusion of a biliary system significantly enhances the model's physiological relevance and predictive capability for drug development.
• This advanced liver-on-a-chip platform shows significant promise for improving in vitro drug discovery and toxicity testing.