Atherosclerosis is the major precursor of cardiovascular disease, the cause of nearly a third of all deaths worldwide. Atherosclerosisbegins with accumulation of cholesterol-carrying lipoproteins on blood vessel walls and progresses to endothelial cell dysfunction, monocyte adhesion, and foam cell formation. We fabricated endothelialized tissue-engineered blood vessels (TEBVs) recapitulating artery functionalities including vasoconstriction, vasodilation, and endothelium activation. We were to emulate the initiation of atherosclerosis by designing branched TEBVs (brTEBVs) of various geometries treated with enzyme-modified low‐density‐lipoprotein (eLDL) and TNF α to induce endothelial cell dysfunction and adhesion of perfused human monocytes. We identify locations of monocyte adhesion under pulsatile flow and characterize the hemodynamics in the brTEBV using particle image velocimetry (PIV) and computational fluid dynamics (CFD). Monocyte adhesion is greater at the side outlets than at the main outlets or inlets and is greatest at larger side outlet branching angles (60° or 80° versus 45°). In PIV experiments, the branched side outlets are identified as atherosclerosis-prone areas where fluorescent particles show a transient swirling motion following flow pulses; in CFD simulations, side outlets with larger branching angles show higher vorticity magnitude and greater flow disturbance than other areas. These results suggest that the branched TEBVs with eLDL/TNF αtreatment provide a physiologically relevant model of early atherosclerosis for preclinical studies.
Dr. Jounghyun Helen Lee is an associate research scientist at the Department of Biomedical Engineering at Columbia University. She earned her BS and MS degrees in Chemistry from Ewha Womans University in Seoul, Korea, and worked for Samsung SDI for several years, during which 12 of her patents were approved. She moved to the US and earned her Ph.D. under Prof. Woo Lee’s direction in Materials Science and Engineering at Stevens in 2010, when she began to see the potential of microfluidics for biological studies. Supported by the NRSA postdoctoral fellowship, she received her post-doctoral training in the field of immunoengineering and microfluidicsat Columbia University,where she continuesto work as a research scientist. Her research interests emphasizemicrophysiological systems for 3D tissue engineering, cancer immunotherapy, and drug delivery and screening.