Hemodynamic characteristics of new blood vessel sprouts using high-fidelity red blood cell resolved simulations

INTRODUCTION: The sprouting of new blood vessels off existing vessels, or sprouting angiogenesis, is ubiquitous at all stages of animal life and in both health and disease. Endothelial cells (ECs) lining blood capillaries move/reorganize in response to local stimuli in the host vessel, such as wall shear stress (WSS) exerted by blood. The newly formed vessels are blind-ended and leaky. While it has long been known that hemodynamics influence sprout growth, this association is largely based on correlative observations or computational estimates based on idealized geometries and reduced-order approaches that fail to capture the 3D details and red blood cell (RBC) dynamics present in vivo. As a result, we hypothesize that unique time dependent and time averaged hemodynamic characteristics exist in vessel sprouts. Revealing such characteristics requires 3D RBC resolved simulations in real sprout geometry. The objective of this work is to model blood flow through capillary sprouts off host vessels using high-fidelity simulations, resolving 3D EC surfaces and physiological permeability of leaky sprouts. Methods: High fidelity RBC resolved simulations were performed using a 3D immersed boundary method based fluid dynamic solver 2 . 3D sprouts were constructed based on the imaging of rat mesenteric microvascular sprouts observed during angiogenic remodeling. The host vessel has a diameter of 20 µm, while the sprout has variable diameters along the sprout length. Individual ECs comprising the sprout walls and representative EC gaps were constructed matching the physiological permeability of leaky sprouts. Simulations were performed spanning a range of physiological shear rates and overall hematocrit levels. Output simulation data were used to quantify key hemodynamic features such as wall shear stress (WSS), velocity distribution, and heterogeneous 3D wall permeability. Data & Results: The findings show that time dependent WSS along the sprout length is mainly influenced by the unsteady movement of RBCs inside the host vessel, with shear rates significantly affecting the magnitude of variation (20 dyne/cm 2 for 100 s -1 shear rate). Time-averaged WSS shows a spatial dependency on shear rates, affecting the average, maximum, and minimum WSS values along the sprout length (the average around 20 dyne/cm 2 and the maximum around 56 dyne/cm 2 for 100 s -1 shear rate). The effects of RBCs inside the host vessels were elucidated using plasma-only simulations, revealing a 3-4 fold increase in WSS along the sprout length due to the presence of RBCs. Reducing the host vessel diameter impacts maximum WSS value, indicating the importance of host vessel diameter on sprout growth. Additionally, unique velocity distributions and sprout permeability due to RBC flow have been observed. Conclusions: Our results provide new characterizations of hemodynamics in blood vessel sprouts. The described WSS patterns (time-dependent and time-averaged), along with velocity and permeability, provide a foundation for better understanding and predicting how new blood vessels grow, and provoke new discussions and studies. References: 1. Hossain et. al, FUNCTION, 2023. 2. Balogh et. al, JCP., 2017. NSF CBET 2309559, NIH R21HL159501, and Expanse at the San Diego Supercomputer Center per NSF Accelerate Award BIO230073. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.