Investigating endothelial responses to changes in vascular structure and fluid shear using organ on chip models

Hemodynamic fluctuations at vessel bifurcation impact the development and progression of atherosclerosis and aneurysms. A novel glass capillary tube-based lithography-free technique was used for fabricating vessel bifurcations with stenosis and aneurysm at the junction of bifurcation, to determine the endothelial response to arterial shear rates in vitro. Using this frugal approach , the angle of bifurcation, lateral angle of aneurysmal dilation and the degree of stenosis were obtained to be 52±3°, 120±10° and 30±6° respectively. Under physiological shear rates of upto 2000 s^-1, observed at areas of 35% stenosis, the highest wall shear rates were observed at the carina when compared to the lateral walls. At 50% aneurysmal dilation, the shear rates dropped to 10-15 s^-1 at perfusion rates of 5μl/min and increase to about 100 s^-1 at 50 μl/min, with the highest shear forces observed when flow divided into daughter channels. The vessel models were endothelialiased for surface expression of adhesion molecule ICAM-1 and VE-cadherin under mechanical forces. At areas of stenosis in vessel bifurcations, the cell-cell junctions remain intact in comparison to straighter vessels, due to reduced pressure at the lumen. Aneurysms demonstrated increased VE-cadherin expression and thus endothelial activation was a likely occurrence at areas of stenosis in vessel bifurcations, due to increased shear forces in comparison to aneurysmal walls that upregulate the expression of adhesion molecules promoting inflammation.