The Effect of Vascular and Erythrocyte Disease States on Interactions in Blood

Abstract

In this work, we developed and used a series of constrained in vitro and ex vivo model systems to explore the transport of particles with respect to highly prevalent diseases: atherosclerosis, malaria, sickle cell disease, and finally hereditary spherocytosis. In a preliminary study, we probed how the progression of malaria through changes in rigidity and concentration of RBCs alone promote transport of mature infected RBCs towards the endothelial wall to avoid splenic clearance. Due to the importance of these two factors (rigid fraction and RBC count) on margination, we questioned how simple transfusion, that affects both simultaneously, can modulate WBC over adherence in sickle cell disease patients. We modelled that by achieving a rigid fraction of 18% led to a 20% reduction in WBC adhesion restoring WBC adhesion to healthy levels. Taking interest in medicine, we developed a novel method for identifying hereditary spherocytosis by analyzing shifts in sedimentation patterns brought about by changes in RBC shape and rigidity. We found that rigid spherocytes having nearly 1.5x the hexactic order of soft discocytes and induce a significant increase in long range order when introduced. Finally, we investigated how vascular targeted carriers interact with large artery curvature that is physiologically relevant to the scale of plaques in atherosclerosis using novel cell culture methods in 3D printed macrofluidic devices. We found curvature plays a significant role in particle transport towards the outer wall of curvature with up to a 5x differential between our inner and outer walls of curvature.Ultimately, we found that changes in flow and RBC rigidity can significantly impact how particles/cells transport in blood both inside and outside the body.