Direct Numerical Simulation of Cellular-Scale Blood Flow in 3D Microvascular Networks

Abstract

We present, to our knowledge, the first direct numerical simulation of 3D cellular-scale blood flow in physiologically realistic microvascular networks. The vascular networks are designed following in vivo images and data, and are comprised of bifurcating, merging, and winding vessels. Our model resolves the large deformation and dynamics of each individual red blood cell flowing through the networks with high fidelity, while simultaneously retaining the highly complex geometric details of the vascular architecture. To our knowledge, our simulations predict several novel and unexpected phenomena. We show that heterogeneity in hemodynamic quantities, which is a hallmark of microvascular blood flow, appears both in space and time, and that the temporal heterogeneity is more severe than its spatial counterpart. The cells are observed to frequently jam at vascular bifurcations resulting in reductions in hematocrit and flow rate in the daughter and mother vessels. We find that red blood cell jamming at vascular bifurcations results in several orders-of-magnitude increase in hemodynamic resistance, and thus provides an additional mechanism of increased in vivo blood viscosity as compared to that determined in vitro. A striking result from our simulations is negative pressure-flow correlations observed in several vessels, implying a significant deviation from Poiseuille's law. Furthermore, negative correlations between vascular resistance and hematocrit are observed in various vessels, also defying a major principle of particulate suspension flow. To our knowledge, these novel findings are absent in blood flow in straight tubes, and they underscore the importance of considering realistic physiological geometry and resolved cellular interactions in modeling microvascular hemodynamics.

ATP Release by Red Blood Cells under Flow: Model and Simulations

“…During their travel in the microcirculation, they experience a cascade of branching vessels. Many numerical studies have been performed in single or multiple bifurcations regarding more or less complex models of blood flow (36)(37)(38)(39)(40)(41). The arterioles are wrapped by smooth muscle cells and are well innervated, so in principle they are capable of controlling their pressure via vasomotion.…”

Physical and geometric determinants of transport in fetoplacental microvascular networks

“…5C), and that the network itself is robust to occlusions of individual vessels (Fig. 5D), which may occur transiently due (for example) to red blood cells lingering at network bifurcations [33]. These predictions await confirmation through more detailed theoretical studies that describe blood rheology in complex geometrical domains, and suitable experimental observations.…”

Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology

“…[ 5 ] In particular, variations in cytoskeletal architecture and the presence/absence of nuclei result in mechanical stiffness differences among RBCs, WBCs, and platelets, which dictate elasticity and deformability of individual cell types. [ 126,127 ] Intercellular collisions occurring in bloodflow cause margination of stiffer WBCs and platelets toward the vessel wall while the softer RBCs flow in the central space. As a result, the EC monolayer frequently encounters adhesive forces (from platelets) and rolling/shearing forces (from leukocytes and neutrophils).…”

“…[ 276 ] This capability is particularly useful when fabricating tortuous, tree‐like vascular geometries with bifurcations, loops, and branches to study hemodynamics and deformation of red blood cells (RBCs). [ 126,127 ]…”