However, microfluidic devices can capture features of the native vasculature such as cellular composition, flow, geometry, and ECM presentation. Traditional in vitro systems poorly recapitulate architectural and dynamic flow properties of in vivo systems. Vaso-occlusions can occur in post-capillary venules hence, the microvasculature is a prime target for SCD therapies. Vaso-occlusive episodes deprive tissues of oxygen and are a major contributor to SCD-related complications unfortunately, the complex mechanisms that contribute to vaso-occlusions are not well understood. These episodes are the result of a combination of processes including inflammation, thrombosis, and blood cell adhesion to the vascular wall which leads to blockages within the vasculature termed vaso-occlusions. This phenomenon is central to SCD pathogenesis as individuals suffering from the disease are plagued by painful vaso-occlusive crises episodes. Upon deoxygenation, hemoglobin polymerizes and triggers RBC remodeling. SCD stems from amutation in the beta globin gene. Microfluidics for investigating vaso-occlusions in sickle cell disease. This work was supported by the NSF grant CBET-0852948 and the NIH grant R01HL094270. Under inflammation, adherent leukocytes may also trap SS4 cells, resulting in vaso-occlusion in even larger vessels. The more adhesive SS2 cells interact with the vascular endothelium and further trap rigid SS4 cells, resulting in vaso-occlusion in vessels less than 15 μm. We further simulate the tube flow of SS-RBC suspensions with different cell fractions. Simulation results indicate that the different cell groups (deformable SS2 RBCs, rigid SS4 RBCs, leukocytes, etc.) exhibit heterogeneous adhesive behavior due to the different cell morphologies and membrane rigidities. Using this model, the adhesive dynamics of single SS-RBC was investigated in arterioles. Based on dissipative particle dynamics, a multi-scale model for the sickle red blood cells (SS-RBCs), accounting for diversity in both shapes and cell rigidities, is developed to investigate the mechanism of vaso-occlusion crisis. While early studies suggested that the crisis is caused by blockage of a single elongated cell, recent experimental investigations indicate that vaso-occlusion is a complex process triggered by adhesive interactions among different cell groups in multiple stages. Vaso-occlusion crisis is one of the key hallmark of sickle cell anemia. Mechanism of vaso-occlusion in sickle cell anemia
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