In vitro platforms for evaluating liver toxicity.

Area of Science:

• Hepatology and Toxicology
• Biomedical Engineering
• Drug Development

Background:

• Drug-induced liver disease (DILD) etiology is debated, often involving immune response and metabolic dysfunction.
• Current animal and in vitro models lack physiological relevance, leading to costly late-stage drug failures.
• Understanding molecular liver injury requires considering interactions between hepatocytes and resident liver cells.

Purpose of the Study:

• To review current macro-scale in vitro liver culture systems.
• To introduce microfluidic systems for physiologically relevant liver modeling.
• To assess liver-on-a-chip platforms for drug response prediction.

Main Methods:

• Discussion of commercialized macro-scale in vitro liver systems.
• Introduction to microfluidic systems mimicking liver dimensions, structure, and function.
• Review of prominent liver-on-a-chip platforms and their drug response capabilities.

Main Results:

• Macro-scale systems have limitations in replicating human liver complexity.
• Microfluidic liver-on-a-chip platforms demonstrate improved physiological relevance.
• These advanced models can measure drug dosage, metabolism, stress, immune, and fibrotic responses.

Conclusions:

• Microfluidic liver-on-a-chip systems represent a significant advancement for predictive toxicology.
• Integration with biosensors and computational models can enhance DILD prediction.
• These human-relevant in vitro models promise to reduce drug development costs and failures.