New Blood Vessel Sprouts and the Unique Hemodynamics Within

The growth of new blood vessels off existing vessels, or angiogenesis, is ubiquitous at all stages of animal life and in both health and disease. New blood vessels commonly form as blind-ended sprouts off of a host vessel through which red blood cells (RBCs) flow. Endothelial cells (ECs) comprising sprout walls are not perfectly sealed to one another, leading to plasma leakage into tissue and facilitating sprout growth. While it is known that hemodynamics influence sprout growth, current knowledge is based on reduced-order approaches which neglect 3D details and RBC-resolved fluid dynamics that are present in vivo. In the current work, we model in vivo microvessel sprouts off host vessels through which RBCs flow using high-fidelity simulations. 3D surface shapes of ECs comprising the sprout walls as well as gaps permitting leakage into surrounding tissue are fully resolved. We consider a range physiological conditions and quantify key hemodynamic features including wall shear stress (WSS), velocity distribution, and heterogeneous 3D wall permeability. 3D WSS patterns are revealed with peaks reaching an order of magnitude higher than the host vessel. Relationships between EC gap geometry and leakage are identified, enabling quantification of permeability that is difficult to measure in vivo. We also quantify the influence of RBCs which can enter sprouts on observed characteristics. Altogether, this work provides new and novel insights into the microenvironment likely experienced by sprouts in vivo.