Date of Award

5-2024

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biomedical Engineering and Sciences

First Advisor

Christopher A. Bashur

Second Advisor

Venkat Keshav Chivukula

Third Advisor

James R. Brenner

Fourth Advisor

Linxia Gu

Abstract

Globally, the annual hemodialysis procedures surpass 1.5 million, emphasizing the vital role of reliable vascular access methods. However, common challenges like access infections and clot-induced blood flow reduction necessitate innovative solutions. This study delved into the potential therapeutic role of carbon monoxide (CO) and its effects on both endothelialization and non-pathogenic bacteria causing infections. The primary focus was evaluating the impact of loading different concentrations of carbon monoxide-releasing molecules (CORMs), specifically CORM diketone 4 (DK4), within 2D spin-coated films on cultured E. coli and endothelial cells. Initial assessments of CO release kinetics from DK4-loaded films demonstrated that the 10% condition exhibited higher release than the 5% condition in the first two batches. These two batches were used for analyzing the impacts on cells. Additional characterization of the spincoated films revealed that increasing DK4 concentration led to higher contact angles. SEM analysis illustrated reduced biofilm maturity in 5% and 10% non-activated DK4 conditions compared to PCL controls, with activation of 10% DK4 resulting in negligible surface bacteria. Preliminary results also suggest benefits for 10% DK4 in other assays, such as decreased colony-forming units (CFU) post-activation and the highest dead/live ratio in planktonic form. Ongoing studies aim to validate these findings, with co-culture investigations underway. These findings promise to enhance vascular access and combat bacterial infections in hemodialysis patients while improving endothelialization.

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