The multi-organ chip--a microfluidic platform for long-term multi-tissue coculture.

Area of Science:

• Biotechnology
• Toxicology
• Microfluidics

Background:

• High demand for new substance testing solutions due to market growth and limitations of current in vitro models.
• Drug-induced liver injury (DILI) often detected late in human chronic testing.
• Controlled microenvironment is crucial for long-term, multi-dose experiments.

Purpose of the Study:

• To develop a microengineered bioreactor for dynamic perfusion and multi-organ co-culture.
• To create a system that better mimics in vivo conditions for cell cultures.
• To enable long-term, repeated substance exposure for improved toxicological assessment.

Main Methods:

• Generation of a microengineered bioreactor with an on-chip pump for dynamic perfusion.
• Co-culturing human liver equivalents (HepaRG, hepatic stellate cells) with human skin punch biopsies for up to 28 days.
• Utilizing cell culture inserts for air-liquid interface culture and topical substance exposure.
• Incorporating vascularization using human dermal microvascular endothelial cells.

Main Results:

• The microbioreactor supported stable, organotypic co-cultures under near-physiologic conditions.
• Long-term cultures (up to 28 days) allowed for repeated substance exposure.
• Vascularization of the microfluidic circuit created a more physiologically relevant vascular model.

Conclusions:

• The developed microbioreactor system offers a promising platform for advanced substance testing.
• It enhances the predictability of toxicological outcomes by mimicking in vivo conditions.
• Enables long-term, multi-dose studies for better assessment of drug-induced liver injury and other toxicities.