Adherent microbial communities, known as biofilms, are a major contributing factor in the incidence of healthcare-associated infections (HCAIs). HCAIs are responsible for annually causing 100,000 deaths and medical expenses estimated to be $35-45 billion. Physical and chemical surface modification techniques are thought to be critical in the fight against biofilm formation within medical settings. Nanoscale structural features have been found to have significant effects on bacterial adhesion and biofilm formation, but their effects on fungal pathogens are less explored. This thesis systematically explores the effect of surface topography in the form of nano and microscale polymeric fibers (~0.4-1.2 µm in diameter) on biofilm formation and virulence of a common HCAI-causing fungal pathogen, Candida albicans. We show that both C. albicans attachment density and differentiation to its virulent phenotype significantly vary with fiber diameter and spacing on polymeric fiber-coated surfaces. We further show that high throughput and high content techniques, such as Raman spectroscopy, can be used to track environmental and physical effects on the organism's resulting morphology and associated virulence. Findings from this thesis will inform the design of antifouling surfaces including implantable medical devices. In a prototypical example, we demonstrate the use of fiber coating to modulate C. albicans attachment on polyurethane, silicone, and latex catheters. / Master of Science / Microbial communities that adhere to surfaces, known as biofilms, are largely associated with incidence of healthcare-associated infections (HCAIs). HCAIs are responsible for annually causing 100,000 deaths and medical expenses estimated to be $35-45 billion. Modification of surfaces using physical and chemical techniques is believed to be critical in the fight against biofilm formation on surfaces within medical settings. Nanoscale structural features have been found to have significant effects on bacterial adhesion and biofilm formation, but their effects on fungal pathogens have not been extensively studied. This thesis focuses on the effect of surface topography, or textures, in the form of nano and microscale polymeric fibers (~0.4-1.2 µm in diameter) on biofilm formation and disease-causing ability, or virulence, of a common HCAI-causing fungal pathogen, Candida albicans. We show that both C. albicans attachment density and differentiation to its virulent form significantly vary with fiber diameter and spacing on polymeric fiber-coated surfaces. We also show that high throughput and detailed imaging techniques, such as Raman spectroscopy, can be used to track environmental and physical effects on the organism's resulting morphology and associated virulence. Findings from this thesis can be used to aid in the design of surfaces that discourage biofilm formation, including implantable medical devices. We demonstrate the use of fiber coating to vary C. albicans attachment on polyurethane, silicone, and latex catheters in one of our studies.

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<p>Bacterial biofilms are problematic in a variety of industries hence strategies for their mitigation have received significant attention. The approach described herein attempts to control bacterial adhesion using silicone-based polymers- (widely used due to their interesting properties)- via manipulation of their surface chemistry to eventually create anti-fouling surfaces. This involved study of the systematic variation of surface wettability and its effect on <em>Escherichia coli</em> (<em>E. coli</em>) adhesion to novel polymers of acrylate-modified silicone surfactant (ACR) with either hydroxyethyl methacrylate (a hydrophilic monomer), or methyl and butyl methacrylate (hydrophobic monomers). It was hypothesized that the systematic variation of ACR would produce surfaces with differing wettability, without changing other surface properties that influence cellular adhesion. Average light transmittance across the range of visible light wavelengths (400-740nm), surface roughness and Shore 00 hardness data were consistent across the ACR-HEMA copolymer series (80-90%, ~2.5 – 5 nm, and 75-95 Shore durometer points, respectively). The same consistency was observed for surface wettability (contact angles = 78-92°) despite varying HEMA content and consequently <em>Escherichia coli</em> (<em>E.coli</em>) adhesion, likely due to system saturation with silicon (as confirmed by EDX). However, wettability of the ACR-MMA-BMA polymers did vary; ≤ 20 wt% and ≥ 80 wt% ACR polymers had contact angles between 67°- 77°, while 20 < x < 80 wt% ACR polymers had increased surface wettability (contact angles 27.6°- 42.9°). <em>E. coli </em>adhesion across the set increased with increasing ACR content, a trend mirrored by the water uptake of the materials but not the contact angle data. These results indicate that <em>E. coli </em>adhesion occurs independently of wettability for these materials and although the effect of the latter on adhesion cannot be deduced, the possible correlation between bacterial adhesion and water uptake suggests that the best antifouling surfaces should not be of materials capable of imbibing significant amounts of water.</p> / Master of Applied Science (MASc)

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