Estimation of 3D Wall Shear Stress in In Vivo Blood Vessel Sprouts Using Red Blood Cell Resolved Simulations

The sprouting of new blood vessels off existing vessels, or angiogenesis, is ubiquitous at all stages of animal life in both health and disease. Endothelial cells lining blood vessel walls move/reorganize in response to stimuli such as wall shear stress (WSS) exerted by blood flow. While it is well known that microcirculatory hemodynamics influence sprout growth, current understanding is based on idealized geometries and pure plasma flow. To address this gap, we performed 3D RBC resolved simulations through digitally reconstructed in vivo blood vessel sprouts. The findings reveal physiologically relevant, time-dependent 3D WSS variations along the sprout length due to unsteady host vessel conditions. We identified how RBCs can enter a sprout and exacerbate WSS characteristics influenced by sprout geometry and hemodynamics. In the absence of RBCs in a sprout, WSS magnitudes varied up to 4 dyne/cm² along the sprout length, but with RBCs, variations increased to as much as 13 dyne/cm². The findings demonstrate that shorter sprouts experience greater WSS, particularly near the tip; meanwhile, smaller host vessel diameters reduce WSS fluctuations, while greater hematocrit and flow strength proportionally increase both WSS magnitudes and fluctuations. Altogether, this work presents a new comprehensive estimation of 3D WSS characteristics within in vivo sprouts influenced by deformable RBCs, offering a foundation for predicting vascular growth.