Double-Layered Microphysiological System Made of Polyethylene Terephthalate with Trans-Epithelial Electrical...

Area of Science:

• Biomedical Engineering
• Drug Development
• Cell Biology

Background:

• Microphysiological systems (MPSs) are emerging alternatives to animal testing in drug development.
• Existing MPS chips face challenges with optical interference and drug absorption.
• Current trans-epithelial electrical resistance (TEER) measurement methods in MPSs lack uniform current density, compromising accuracy.

Purpose of the Study:

• To develop an electrode-integrated MPS chip for accurate TEER measurement with uniform current distribution.
• To minimize drug absorption issues associated with traditional MPS materials.
• To create a reliable platform for assessing barrier integrity and drug responses in non-animal drug testing.

Main Methods:

• Finite element method simulation was used to optimize electrode patterns.
• A polyethylene terephthalate (PET)-based chip was fabricated by laminating PET films, porous membranes, and patterned gold electrodes.
• The chip's performance was evaluated using a perfused Caco-2 intestinal model and drug exposure (staurosporine).

Main Results:

• The developed MPS chip demonstrated uniform current density and reduced drug absorption.
• TEER measurements correlated with Caco-2 cell monolayer formation and subsequent villi-like structure development.
• Dose-dependent reduction in TEER by staurosporine indicated tight junction disruption, validated by immunostaining.

Conclusions:

• The study presents a reliable TEER measurement MPS platform with enhanced accuracy and minimal drug absorption.
• This system effectively monitors barrier integrity and drug responses, supporting non-animal drug testing.
• The optimized MPS chip design advances the development of in vitro models for drug discovery.