Liver-on-a-Chip: Searching for a Balance Between Biomimetics and Functionality.

Area of Science:

• Biomedical Engineering
• Drug Discovery
• Toxicology

Background:

• Animal models often fail in predicting drug efficacy and safety due to species-specific differences.
• Organ-on-a-chip (OOC) systems, especially liver-on-a-chip (LOC), aim to mimic human physiology at the microscale.
• LOC technology presents a potential solution to improve preclinical drug assessment.

Purpose of the Study:

• To review and discuss the architectural design and validation of liver-on-a-chip systems.
• To identify trends in balancing biomimetic complexity with functional performance in LOC devices.
• To explore the future direction of LOC technology for drug development.

Main Methods:

• Literature review of existing liver-on-a-chip models.
• Classification of LOC designs based on configuration complexity into five groups: flat one-channel, flat two-channel, vertically stacked multilayered, hexagonal-patterned, and multi-well chips.
• Analysis of the trade-offs between architectural complexity and practical functionality.

Main Results:

• LOC designs vary significantly in complexity, categorized into five main types.
• Increasing architectural complexity aims to better recapitulate liver histology and function.
• Industrial preferences lean towards simpler, more flexible LOC designs for scalability.

Conclusions:

• Future liver-on-a-chip designs need to prioritize standardization and sustainability.
• Simplifying certain liver characteristics in LOCs may be necessary for market adoption.
• Optimized LOC designs can facilitate integration into clinical drug development pipelines.