Combined Bactericidal/Bacterial Adhesion-Resistant Coatings through Nitric Oxide Release Public Deposited

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  • March 22, 2019
Creator
  • Storm, Wesley Langdon
    • Affiliation: College of Arts and Sciences, Department of Chemistry
Abstract
  • In response to the health and economic burdens associated with implant-related infections, researchers have developed coatings that resist bacterial adhesion and/or kill bacteria. Herein, the synthesis of coatings that release nitric oxide (NO) to inhibit bacterial adhesion and kill bacteria are described. In order to expand the clinical utility of NO-releasing surfaces, xerogels were synthesized from N-diazeniumdiolate-modified silane precursors. Release kinetics and totals were tunable through careful selection of the silane precursor and its concentration, respectively. To demonstrate the versatility of this approach, NO-releasing xerogels were cast as outer membranes on glucose sensors. The sensors exhibited a linear response towards glucose and maintained glucose sensitivity in phosphate buffered saline for up to one week. Active and passive antimicrobial surface approaches were combined by synthesizing NO-releasing superhydrophobic xerogels. These reduced viable adhesion of Pseudomonas aeruginosa by two orders of magnitude. Release of NO conferred biocidal properties to the coating, while superhydrophobicity reduced bacterial adhesion. Furthermore, the superhydrophobic coatings were also used to extend drug release rates. The release of two antibacterial agents simultaneously (silver and NO) was pursued as a strategy for enhancing bacterial killing. To this end, xerogels were synthesized that released silver and NO at doses sufficient to kill Pseudomonas aeruginosa and Staphylococcus aureus. Confocal microscopy experiments revealed that NO primarily operated by reducing bacterial adhesion, while silver actively killed bacteria. Together, the two agents killed bacteria more effectively than either agent alone. Poly(amido amine) dendrimers that release NO were used as dopants within polyurethane dispersions to make films and electrospun fibers. The NO flux from these materials could be tuned for antimicrobial or wound-healing purposes. Independent tuning of NO-release and hydrophobicity through multiple surface modifiers was used to minimize leaching of the dendrimers from polyurethane fibers while extending their NO-release duration.
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  • In Copyright
Advisor
  • Schoenfisch, Mark H.
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill
Graduation year
  • 2013
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