Emulating Early Atherosclerosis in a Vascular Microphysiological System Using Branched Tissue-Engineered Blood...

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Vascular Biology

Background:

• Atherosclerosis involves lipoprotein accumulation, endothelial dysfunction, and monocyte adhesion.
• Tissue-engineered blood vessels (TEBVs) can model artery functions.
• Early atherosclerosis mechanisms require better in vitro models.

Purpose of the Study:

• To emulate early atherosclerosis initiation using branched TEBVs (brTEBVs).
• To investigate the impact of geometry and flow on monocyte adhesion in brTEBVs.
• To identify atherosclerosis-prone regions within brTEBVs.

Main Methods:

• Fabrication of branched TEBVs with varying geometries.
• Treatment of brTEBVs with enzyme-modified low-density-lipoprotein (eLDL) and TNF-α.
• Perfusion of human monocytes under pulsatile flow.
• Characterization using particle image velocimetry (PIV) and computational fluid dynamics (CFD).

Main Results:

• Monocyte adhesion was significantly higher at side outlets compared to inlets/main outlets.
• Increased side outlet branching angles (60°, 80°) correlated with greater monocyte adhesion.
• PIV and CFD identified side outlets, especially those with larger angles, as regions with flow disturbances and higher vorticity, correlating with monocyte adhesion.
• Branched side outlets were identified as atherosclerosis-prone areas.

Conclusions:

• Branched TEBVs treated with eLDL/TNF-α provide a physiologically relevant model for studying early atherosclerosis.
• Geometric factors, specifically larger branching angles, significantly influence monocyte adhesion in brTEBVs.
• This model can be utilized for preclinical studies of atherosclerosis initiation and potential interventions.