The general goal of the proposed research is to improve the understanding of inflammation by characterizing mechanistic interactions between neutrophil adhesion and local hydrodynamic forces in converging post-capillary venules and venular networks. Post-capillary venules are a highly branched network of vessels in the microcirculation that play an important role in the inflammatory response. Studies have shown that microcirculatory disorders and inflammation accompany a large number of cardiovascular diseases. However, the mechanistic links between neutrophil adhesion and local hydrodynamic forces are not well understood. The proposed research seeks to establish these mechanistic links using a combination of in vivo data analysis, in vitro experimentation, and computational fluid dynamics. In vivo data analysis will provide vital information about the distributions of neutrophils in post-capillary convergences in an intact physiological system and provide the geometric parameters needed for computational analysis and microfabrication of the in vitro experimental system. In vitro experiments with microspheres and functionalized surfaces in microfabricated convergences will provide a controlled environment to study distributions of adherent cells. The in vitro experiments will also provide vital information about the fundamental fluid physics associated with convergences and provide information to validate the CFD model. The CFD analysis will provide additional information about the fundamental fluid dynamics in the convergence that cannot be obtained from physical experimentation. By coupling the three approaches, information about the distributions of adherent neutrophils can be correlated with fundamental fluid physics and used to elucidate the mechanistic links between neutrophil adhesion and local hydrodynamic forces. Understanding the interactions between fluid forces and cellular adhesion holds great promise for advancing the understanding of the inflammatory response and could aid in the development of targeted drug or stem cell delivery methods or development of microsensors or microrobotic devices. Inflammation has received a great deal of attention in recent years since a number of cardiovascular diseases such as hypertension and diabetes have an inflammatory component. The proposed work would provide additional information about the inflammatory response in microvascular vessels, locations that have been associated with cardiovascular diseases. Information about preferred locations for adhesion in venular branches could be used to further the understanding of the inflammatory response and to develop novel treatment strategies to help combat the growing presence of cardiovascular disease prevalent in today's society. ? ? ?
| Jung, John J; Grayson, Korie A; King, Michael R et al. (2018) Isolating the influences of fluid dynamics on selectin-mediated particle rolling at venular junctional regions. Microvasc Res 118:144-154 |
