Study Objective: To predict flow of blood cells and capillary hemodynamics and to understand their role in angiogenesis.Hypothesis: Red blood cell flow dynamics affects the growth and remodeling of angiogenic vasculature.Methodology: A high-fidelity 3D computational model is used to simulate flow of blood cells through microvascular networks in retinal angiogenesis. The model accurately resolves deformation of each individual blood cells in flow and accurately model the mouse retinal angiogenic vasculature as obtained from in vivo images. The model accurately predicts hemodynamic parameters, such as, blood cell velocity, hematocrit and 3D profiles of wall shear stress (wss) in every vessel of the angiogenic network.Data: The model simulates blood cell flow over nearly 700X500 μm 2 area containing hundreds of angiogenic vessels (dia. 2--30 μm, including vessel sprouts) and more than 3000 cells at any instant of time. We specifically focus within ~500 μm from the leading angiogenic front. Predicted cell velocity ranges from 0-5 mm/s, hematocrit 0-30%, and wss 0-120 dyn/cm 2 . Summary Results: We found that there are specific vascular pathways formed by multiple vessels that are rich in flowing blood cells while majority of the remaining vessels have very few blood cells or no cells at all. These high-RBC channels are also the vessels with higher wss. Furthermore, we found that a region of ~100 μm from the leading edge of the retinal vasculature, where most sprouting vessels are seen, are devoid of any red blood cells. Additionally, we found red cell clogging many narrow vessels at larger distances from the leading front of the vasculature. Finally, by comparing simulations with plasma-only fluid and whole blood, we predicted that flow distributions in the two cases are very different. This difference arises due to the presence of the red cells which alters the flow pattern by clogging many vessels.Conclusions: While hypoxia is one major cause that drives angiogenesis, and red blood cells are the oxygen carrier, the present computational model predicts a possible mechanistic role of red cells in the growth and remodeling of angiogenic vasculature. Specific flow channels rich in flowing red cells and with high wss are found that are likely to survive while others devoid of red cells and with low wss are likely to regress. The absence of red cells over a large region near the leading front of the angiogenic vasculature suggest hypoxic growth in this region. Predicted vessel clogging by red cells suggests altered and redistributed flow during remodeling Funding Information: Funded by NIH (EY033003) and NSF (CBET 2521359). This abstract was presented at the American Physiology Summit 2026 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.
Bagchi et al. (Fri,) studied this question.