Celebrating Scholarship and Creativity Day (2018-)

Document Type

Presentation

Publication Date

4-30-2026

Disciplines

Biochemistry, Biophysics, and Structural Biology | Chemistry

Advisor

Claire Otteson

Abstract

The purpose of this thesis is to explain the current state of alternative oxygen carriers and propose a new hemoglobin-based oxygen carrier (HBOC) as a blood substitute/ blood therapeutic. Blood donation has drawbacks: risk of spread of infection, short storage time, and blood typing, and the current shortage. There are several possible modifications for hemoglobin to create a carrier (HBOC) which address specific issues related to allowing free hemoglobin to exist extra cellularly. One issue to address is vasoconstriction caused by nitric oxide scavenging, which has been solved by increasing the molecular weight of the HBOC via (co)polymerization, or by intramolecularly crosslinking hemoglobin subunits to maintain its full tetrameric configuration. Increasing retention time is another issue; adding polyethylene glycol polymers to hemoglobin via PEGylation has been successful for this. Another issue that has been addressed is the creation of reactive oxygen species, mainly by copolymerizing an enzyme to reverse the synthesis of these species. Minimizing hypertensive effects is the main gap in clinical research, which could be addressed by combining several methods. Transfusion of a non-toxic HBOC would be able to acutely replace blood transfusion in scenarios when blood is not available. Alternative carriers do not have previously described issues and also have implications for alleviating the blood-shortage crisis. Research also suggests unique therapeutic effects like oxygenating hypoxic tumors to stunt angiogenesis, making them easier to manage due to their smaller size than red blood cells. In the future, more work could be done to assess the stability of this proposed carrier to determine if stability also plays a role in the scavenging of nitric oxide via break down of the polymer and possible extravasation into epithelial walls.

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