Date of Award

Spring 5-3-2024

Level of Access Assigned by Author

Open-Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical Sciences

Advisor

Caitlin Howell

Second Committee Member

David Neivandt

Third Committee Member

Ling Cao

Additional Committee Members

Robert Wheeler

William Gramlich

Abstract

Catheter-associated urinary tract infection (CAUTI) stands out as one of the most prevalent hospital-acquired infections, the long-term presence of urinary catheters in patients elevates the risk of contracting CAUTI by 80-100%. Despite the widespread use of antibiotics, the current standard of care, effective treatment is still challenging due to formation of biofilms by uropathogens on catheter surfaces, which shield the pathogens from both antibiotics and the immune system. Silicone urinary catheters infused with silicone oil have emerged as a promising alternative, diminishing microbial adhesion to catheter surfaces, bladder colonization, and systemic spread. In this dissertation, we provided a comprehensive account of the development of these catheters, detailing their physical properties throughout the infusion process, such as length, inner, and outer diameter. We demonstrated that these parameters are dependent on infusion duration, with full infusion resulting in a significant increase in these properties. This highlights the crucial role of manufacturing controls, as catheters must be customized in size for each patient's needs. While fully infused catheters have proven effective in repelling pathogen adhesions in mouse models, the potential leakage of silicone oil into the host system is undesirable. Therefore, we fabricated liquid-infused catheters devoid of a free liquid layer, achieved by either removing excess silicone oil from fully infused samples through absorption or through partial infusion. We demonstrated the efficacy of our methods in reducing the amount of free liquid layer on infused catheters through confocal microscopy. Our analysis revealed a significant decrease in the thickness of the liquid layer from approximately 60 μm to <1 >μm. Additionally, by reducing the infusion time, we were able to produce catheters infused with varying percentages, resulting in different quantities of silicone liquid incorporated into the polymer matrix. Furthermore, we investigate their efficacy in repelling protein and bacterial adhesion. Our findings reveal that fully infused catheters, with the free liquid removed, exhibit equal efficacy in reducing host protein fibrinogen and the common uropathogen E. faecalis adhesion when compared to fully infused catheters with free liquid. Additionally, they demonstrate a substantial ~64% decrease in liquid loss into the environment. Partially infused catheters also show reduced liquid loss as the total liquid content decreases, with samples infused to 70-80% of their maximum capacity displaying an impressive ~85% reduction in liquid loss compared to fully infused controls. Moreover, samples infused above 70% exhibit no significant increase in fibrinogen or E. faecalis adhesion. Together, our findings suggest that eliminating the free liquid layer, either mechanically or through partial infusion, holds promise in reducing liquid loss from liquid-infused catheters while maintaining functionality.

Download

Share