A bioengineered array of 3D microvessels for vascular permeability assay.

Area of Science:

• Biomedical Engineering
• Vascular Biology
• Microfluidics

Background:

• Vascular barrier dysfunction is linked to diseases like cancer and fibrosis.
• Existing in vitro models lack the realistic barrier properties of in vivo vessels.
• Accurate measurement of vascular permeability is crucial for understanding disease and drug efficacy.

Purpose of the Study:

• To develop a reliable microfluidic platform for measuring microvessel permeability.
• To create a model that mimics in vivo vascular barrier properties.
• To enable high-resolution, high-throughput permeability measurements and drug screening.

Main Methods:

• Engineering tubular, perfusable microvessels using natural angiogenic processes on a microfluidic chip.
• Utilizing high-resolution, live-cell time-lapse imaging for dynamic monitoring.
• Measuring permeability coefficients and assessing cell-cell junction protein expression (ZO-1, Claudin-5, VE-cadherin).

Main Results:

• The engineered microvessels demonstrated reliable barrier properties with a permeability coefficient of 1.55×10⁻⁶ cm/s.
• The model replicated in vivo vessel characteristics, including cell-cell junction expression and response to agonists (histamine, TNF-α).
• Anti-VEGF (bevacizumab) treatment normalized tumor microvessel hyperpermeability, validating the model's responsiveness.

Conclusions:

• The microfluidic chip provides a robust and realistic in vitro model for assessing vascular permeability.
• This platform facilitates fundamental research in vascular biology and accelerates drug screening for permeability-related disorders.
• The developed method offers a valuable tool for evaluating drug effects on microvessel function.