Endothelium-on-chip for vascular dysfunction: it takes two to tango.
Endothelial cells, lining the blood vessel lumen, experience laminar shear stresses in straight arterial sections, whereas branch points, regions downstream of curved sections, and bifurcations are subjected to unsteady or pulsatile, and spatially developing complex stresses. Vessel curvature results in secondary flows caused by an imbalance between centrifugal forces and the radial pressure gradients. Early atherosclerotic lesions often develop in disturbed flow regions within arterial curvatures and bifurcations. A shear rosette, representing temporal variations in the wall shear stress vectors along the principal and orthogonal directions in these regions, is a useful method to characterize flow variations along the axial and secondary flow directions. Elucidating the mechanisms underlying endothelial cellular responses to flows is essential in delineating factors which may be involved in disease pathophysiology. I will discuss our recent efforts in the development of a novel endothelium-on-chip device which uses “controlled” disturbed flows. I will present mechanobiological results from this device using human aortic endothelial cells. Finally, I will discuss some recent directions from my lab in linking biophysical properties of the monolayer to the underlying function. Such studies may potentially be useful in reducing our reliance on animal trials and in assessing therapeutics for personalized medicine.