An in vitro device for evaluation of cellular response to flows found at the Apex of arterial bifurcations

Intracranial aneurysms (ICA) are abnormal dilations of the cerebral arteries, most commonly located at the apices of bifurcations. The ability of the arterial wall, particularly the endothelial cells forming the inner lining of the wall, to respond appropriately to hemodynamic stresses is critical to arterial health. ICA initiation is believed to be caused by a breakdown in this homeostatic mechanism leading to wall degradation. Due to the complex nature of this process, there is a need for both controlled in vitro and in vivo studies. Chung et al. developed an in vitro chamber for analyzing the response of biological cells to the hemodynamic wall shear stress fields generated by the impinging flows found at arterial bifurcations [7, 6]. Here, we build on this work and design an in vitro flow chamber that can be used to reproduce specific magnitudes of wall shear stress (WSS) and gradients of wall shear stress. Particular attention is given to reproducing spatial distributions of these functions that have been shown to induce pre-aneurysmal changes in vivo [38]. We introduce a measure of the gradient of the wall shear stress vector (WSSVG) which is appropriate for complex 3D flows and reduces to expected measures in simple 2D flows. The WSSVG is a scalar invariant and is therefore appropriate for use in constitutive equations for vessel remodeling in response to hemodynamic loads [34, 35].