A tunable microfluidic 3D stenosis model to study leukocyte-endothelial interactions in atherosclerosis

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Microfluidics

Background:

• Atherosclerosis is a chronic inflammatory vascular disease causing heart attack and stroke.
• Endothelial dysfunction and vessel narrowing are key pathological features.
• Current models lack the complexity to fully replicate the atherogenic microenvironment.

Purpose of the Study:

• To develop and validate a tunable 3D microfluidic model of atherosclerosis.
• To investigate leukocyte-endothelial interactions under various stenosis conditions.
• To explore the potential of leukocytes as biomarkers for inflammatory risk assessment.

Main Methods:

• Pneumatic control to create 0%, 50%, and 80% vascular constrictions.
• Fluid simulation and bead perfusion to characterize flow and shear stress.
• Perfusion of THP-1 monocytes and whole blood through the microfluidic device with inflamed endothelium.

Main Results:

• Non-uniform flow and shear stress at the stenosis influenced monocyte adhesion patterns.
• Differential expression of ICAM-1 was observed at the constriction region.
• Increased leukocyte rolling and adherence occurred at stenotic regions in both healthy and inflamed endothelium.
• Leukocyte adhesion showed a dose-dependent response in blood samples, correlating with inflammation levels.

Conclusions:

• The 3D stenosis chip accurately recapitulates key aspects of the atherogenic microenvironment.
• Hemodynamics and leukocyte-endothelial interactions are critical in atherosclerosis development.
• The microfluidic device shows promise for point-of-care blood profiling for vascular diseases.