Integrated Multiphase Blood Flow Modeling and Experiments Towards Predicting Microvascular Growth

This award aims to advance current understanding of how new blood vessels grow in the body. Such growth is central to many processes in health and disease, from embryonic development and natural changes and repairs as the body ages, to diabetes, heart disease, and tumor growth in cancer. Despite the importance, little is currently known about the three-dimensional biophysical mechanisms driving new vessel growth in real environments. To address this need, this project will develop new data-driven models within an in-house state-of-the-art simulation platform, integrating high-fidelity biophysical simulation with high-resolution imaging of real blood vessel networks undergoing growth and adaptation. Analyses will be performed to elucidate characteristics of the fluid dynamics and biophysics underlying this growth behavior at a new level of detail, towards enabling predictive models. This project will provide the research community with new data-driven models and studies which integrate concepts across disciplines, and provide opportunities to engage the local community, and foster mentorship and education of students at various levels.The growth of new blood vessels off existing vessels, or angiogenesis, occurs in the microcirculation where vessel diameters are similar in size to the individual red blood cells which comprise blood. While it is known that fluid dynamics and shear stresses drive vascular function, current understanding of angiogenic hemodynamics is based on reduced-order approaches which neglect essential three-dimensional cell-scale details of blood flow. Angiogenic vessel networks and new vessel sprouts have uniquely complex three-dimensional geometries through which red blood cells flow and squeeze. Wall shear stress patterns due to these considerations are largely unknown, along with other tissue-side factors and coupled interactions expected to influence angiogenic behavior. The goals of this project include discovering shear stress patterns which emerge in real angiogenic vessel networks through high-fidelity red blood cell-resolved fluid simulations, elucidating the fluid mechanics within new vessel sprouts and connections to growth patterns, and developing a new three-dimensional dynamic multiphysics sprout model which couples porous media tissue transport with microvascular hemodynamics to enable vessel growth through tissue. Potential contributions resulting from this work include helping to predict tumor growth patterns and guiding new treatment approaches, or enabling earlier identification of problems during embryonic development.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.