(4nc) The Effect of Vascular and RBC Disease States on Particle Interactions

Blood is a complex multiphase fluid composed primarily of RBCs, WBCs, and plasma. Interactions between these groups is vital for transport of everything from nutrients, to oxygen, to waste, and even immune cells. To achieve this, cells must be able to navigate a winding maze of arteries (mm scale) all the way down to capillaries (um scale). Disease states such as heart disease, sickle cell disease, hereditary spherocytosis, or even malaria can directly change how blood interacts within itself and therefore damage this delicate balance needed for transport. My work seeks to elucidate: 1) How drug particles and genes interact with the lumen in 3D printed in vitro models of large arteries with applications in atherosclerosis 2) How rigid RBCs marginate in the capillaries and cause changes in WBC adhesion and function

I have developed a method for growing live cells in complex large geometries using a commercially available 3D printer. With this method I have been able to grow highly shear resistant monolayers of both human umbilical vein endothelial cells (HUVEC) and smooth muscle cells (SMCs) without the need for bioprinting nor fixing. I found that model polymeric drug adhesion is significantly impacted by channel curvature in channels that were dimensionally relevant to the carotid artery. This curvature has direct parallels to how particles would bind to an obstructive plaque that creates artificial curvature. Further, I used this model to see how different sex-linked genetic traits in SMCs interact with their ability to withstand shear and how that could impact plaque erosion (more common in females) or plaque rupture (more common in males).

Many diseases cause RBCs to become more rigid. Rigid RBCs contribute to a number of complications such as increased clotting, increased risk for capillary occlusions, decreased O₂ delivery, systemic inflammation, organ damage, anemia, reduced WBC adhesion, and reduced quality and length of life. I primarily studied two diseases malaria and sickle cell disease. First, I developed and quantified an in vitro method for modelling the rigidity of malaria cells by artificially rigidifying them with peroxides. Then using confocal microscopy, I was able to measure where the infected model cells were in flow finding that in far extents of the disease more mature cells based on rigidity alone are able to access the lumen wall. Second, I worked with SCD patients that were receiving transfusions. By performing, parallel ex vivo transfusion I was able to show that the extent of transfusion greatly impacts a patients WBC adhesion following the transfusion.

Research Interests

• Hemodynamics
• Drug delivery
• Tissue and disease modelling
• Vascular engineering
• 3D printing

Teaching Interests

• Fluid mechanics
• Transport phenomena
• Promoting first generation and disadvantaged college students like myself