Paroxysmal Permeability Disorders: Development of a Microfluidic Device to Assess Endothelial Barrier Function

Area of Science:

• Biomedical Engineering
• Vascular Biology
• Microfluidics

Background:

• Paroxysmal Permeability Disorders (PPDs) involve transient increases in endothelial permeability without inflammation or injury.
• PPDs encompass conditions like primary angioedema and systemic capillary leak syndrome.

Purpose of the Study:

• To validate a microfluidic device for studying endothelial permeability under dynamic flow conditions.
• To establish a model system for investigating PPD mechanisms.

Main Methods:

• A microfluidic device with 30μm channels was designed and fabricated.
• Human Umbilical Vein Endothelial Cells (HUVECs) were cultured under shear stress (~0.2 Pa).
• Endothelial permeability was assessed by monitoring fibronectin matrix fluorescence using confocal microscopy after perfusing with biotinylated fibronectin and FITC-avidin.

Main Results:

• The microfluidic system maintained physiologically relevant shear stress.
• Low fluorescence was observed with normal medium or plasma perfusion.
• Perfusion with bradykinin induced a significant increase in fibronectin matrix fluorescence, indicating heightened permeability.

Conclusions:

• The developed microvasculature model accurately replicates physiological flow conditions for endothelial studies.
• This microfluidic device is a promising tool for elucidating the mechanisms of PPDs, particularly those involving bradykinin.
• The model facilitates research into endothelial barrier function and related disorders.