3D hepatic mimics - the need for a multicentric approach.

Area of Science:

• Hepatology
• Toxicology
• Biomedical Engineering

Background:

• The liver is a primary site for drug metabolism, making it susceptible to drug-induced liver injury (DILI).
• Failure to identify drug hepatotoxicity early leads to significant clinical and economic consequences, including drug withdrawal during trials.
• Accurate preclinical toxicity prediction is essential for efficient drug development.

Purpose of the Study:

• To review existing and emerging technologies for developing in vitro liver models.
• To explore various approaches for mimicking the liver's functional and structural complexity in vitro.
• To highlight the importance of these models in predicting drug-induced liver injury during preclinical stages.

Main Methods:

• Description of diverse technologies employed in creating advanced in vitro liver models.
• Analysis of strategies to replicate key hepatic microarchitectural features, such as sinusoids and bile canalicular systems.
• Discussion of methods to mimic the liver's acinar structure and metabolic zonation.

Main Results:

• Identification of multiple technological platforms for in vitro liver model development.
• Demonstration of approaches that successfully mimic critical liver microenvironments and cellular functions.
• Emphasis on the potential of these models to improve the accuracy of DILI prediction.

Conclusions:

• Advanced in vitro liver models are vital for accurate preclinical assessment of drug hepatotoxicity.
• Mimicking the liver's complex architecture and function in vitro is achievable through various technological innovations.
• The development and application of these models can significantly reduce drug development failures due to unforeseen liver toxicity.