Mechanobiology of Hemoglobin-Based Artificial Oxygen Carriers

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Artificial oxygen carriers (AOCs) were initially developed as red blood cell substitutes for transfusion and recently as oxygen therapeutics. They can reduce the harmful side effects of transfusion, such as immunoreaction and inflammation from the donated blood, or to enable life-saving surgeries in patients when donated blood becomes a sparse source. However, development of safe and effective AOCs to replace physiological human red blood cells is challenging. This award supports the research on AOCs to better understand their behavior and performance after entering blood circulation. The results from this project will provide useful knowledge that can be used to develop of safer AOCs products. The research methods can be used to predict the post-transfusion performance of blood substitutes or evaluate the effects of drug treatment on blood circulation. This research is highly interdisciplinary, involving knowledge and training in microfabrication, biochemistry, microfluidics, bioengineering and materials science. It will help broaden participation of underrepresented groups in research. Research findings from this project will be integrated into undergraduate and graduate bioengineering courses, as well as the outreach activities with K-12 students and science teachers. Prolongation of AOCs survival and prevention of transfusion-associated complications are grand challenges in transfusion medicine. Mechanobiology of AOCs, linking biochemistry and systematic response post transfusion, has not been well-studied. The goal of this project is to address several important questions regarding the post-transfusion behavior of AOCs and the potential impacts on the blood vessels, using a multi-scale experimental approach. First, the fatigue of AOCs will be characterized by subjecting them to cyclic hypoxia and shear stresses at single-cell level using a unique and general biomechanical testing platform. Then, the dynamic interactions between AOCs and physiological cells will be studied under oxidative damage and nitric oxide treatments, using in vitro models of blood circulation replicating cellular, hemodynamic and gaseous microenvironment of capillaries and arterioles. Finally, he blood flow behavior, onset and progression of vessel injury will be measured while AOCs circulate in concert with physiological blood cells in a microfluidics-based pulmonary microvasculature model. This study will provide a fundamental understanding of the biomechanical mechanisms underlying the failure of AOCs, inflammatory response, and relevant therapeutic interventions.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.