Three-Dimensional Shear Stress Characteristics in Angiogenic Microvascular Networks Revealed Through Red Blood Cell-Resolved Modeling Based on Real Image

Introduction: Angiogenesis, the process of growing new blood vessels from existing vessels, generally occurs in response to local stimuli. Predominant among these is the wall shear stress (WSS) exerted by flowing blood. Endothelial cells (ECs) line vessel walls and can sense and respond to external forces 1 . 3D WSS characteristics experienced in angiogenic microvascular networks with complex surface topologies, however, are unknown. Recent work 2 demonstrated significant WSS variations due to both geometric vessel complexity and the presence of red blood cells (RBCs). Such findings drive our hypothesis that WSS behavior unique to angiogenesis may exist but requires high-resolution modeling to reveal. The objective of this work is to determine 3D WSS spatial characteristics in angiogenic microvascular networks by integrating high-fidelity simulation with real image data. Methods: RBC-resolved simulations were performed using a 3D immersed boundary method fluid dynamics solver 3 which resolves flow and 3D RBCs with high fidelity. Complex 3D networks were constructed based on image data, with network comprised of 150 vessels. Approximately 1000 RBCs were simulated in a network, with each RBC discretized by 5120 finite elements. Angiogenic microvascular network imaging was performed on rat mesenteric tissues harvested post the stimulation of angiogenesis via 48-80 mast cell degranulation. Data & Results: Output simulation data includes WSS values at 7 million wall points defining the network surfaces, resulting in detailed 3D WSS contours. Significant WSS heterogenity is observed in both space and time. For time-average behavior, WSS values ranged from 0.014 to 225 dyne/cm 2 over network vessels. WSS contours over the whole network reveal network-level variations. Within each vessel, the standard deviation of WSS (quantifying spatial variation) averaged 15 dyne/cm 2 , and reached 55 dyne/cm 2 in some vessels. Such variations in local regions occurred over sub-EC length scales. Temporal WSS fluctuations among wall points within vessels and local regions reached 120 dyne/cm 2 . Conclusions: New findings from this work reveal significant WSS variations can occur in angiogenic microvascular networks at sub-EC length scales. The results provide a new characterization of the EC microenvironment during angiogenesis and provoke consideration of complex temporal and spatial profiles when probing EC responses in experiments. References: 1 Song et. al, PNAS, 2011. 2 Balogh et. al, Phys.Rep., 2019. 3 Balogh et. al, JCP, 2017. This work was supported by funding from the National Institute of Aging (Grant number R01AG049821), and computational resources on NJIT’s Lochness Cluster. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.