Reversible Cavitation-Induced Junctional Opening in an Artificial Endothelial Layer

Area of Science:

• Biomedical Engineering
• Drug Delivery Systems
• Cellular Biology

Background:

• Targeting pharmaceuticals across the endothelial barrier is essential for effective drug delivery.
• Cavitation-assisted permeation offers a promising method for transiently opening intercellular junctions.
• Understanding ultrasound and microbubble interactions is key to controlling endothelial barrier permeability.

Purpose of the Study:

• To investigate and quantify the impact of ultrasound-excited microbubbles (stable cavitation) on endothelial integrity.
• To assess the reversibility of endothelial barrier changes induced by cavitation.
• To validate a vessel-on-a-chip platform for measuring cavitation-enhanced endothelial permeability.

Main Methods:

• Utilized a vessel-on-a-chip model with endothelial cells cultured under physiological shear stress.
• Employed immunofluorescence microscopy with vascular endothelial cadherin staining to monitor vascular integrity.
• Quantified interendothelial gap formation and area as a function of ultrasound pressure amplitude.

Main Results:

• Microbubbles significantly amplified the ultrasound effect, inducing interendothelial gaps and barrier permeabilization.
• The total gap area increased significantly with increasing pressure amplitude compared to controls.
• The induced gap opening was fully reversible, with barrier function returning to baseline levels within 45 minutes post-insonication.

Conclusions:

• The integrated vessel-on-a-chip platform enables precise and repeatable in vitro assessment of cavitation-enhanced endothelium permeability.
• Stable cavitation via ultrasound and microbubbles effectively opens endothelial barriers reversibly.
• This technology holds potential for validating ultrasound irradiation protocols for in vivo drug delivery applications.