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|Title:||Metal ions-based layer-by-layer coatings for antibacterial applications||Authors:||Lim, Yun||Keywords:||Engineering::Bioengineering||Issue Date:||2022||Publisher:||Nanyang Technological University||Source:||Lim, Y. (2022). Metal ions-based layer-by-layer coatings for antibacterial applications. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/161059||Abstract:||The increasing incidence of nosocomial infections and the emergence of multi-drug resistant pathogens have complicated existing treatment regimes. Along with the diminishing antibiotics pipeline, scientists have urged for the development of alternative antimicrobials that are able to mitigate these challenges. The recent resurgence of metals as potential therapeutics has been garnering attention due to their ability to offer a broad range of antimicrobial actions: reactive oxygen species production from redox or catalytic actions, as well as interference with biological functions via exchange or release of ligands. As opposed to organic antibiotics that usually target a specific pathway, inorganic metal-based therapeutics are able to simultaneously exert their disruption on multiple metabolic pathways. Concurrently, the simple and well-established layer-by-layer technique, has emerged as one of the most versatile platforms to develop or coat antimicrobials onto a wide range of substrates - including cotton gauze dressings for wounds, orthopedic implants, or medical devices such as catheters or pacemakers. Herein, this thesis proposes the incorporation of inorganic metals as bioactive agents into the proposed antibacterial dressings via the facile and versatile layer-by-layer (LBL) technique. The unique roles of metal ions as alternative antibacterial and antibiofilm therapeutics against Gram-positive and Gram-negative pathogens will subsequently be studied. The first project evaluates the role of ferrous ions as a catalyst to spontaneously generate hydroxyl radicals for the eradication of pathogens. The in-situ Fenton-based conversion of hydrogen peroxide with mild antibacterial ability to highly reactive and bactericidal hydroxyl radical demonstrated improved antibacterial efficacy of the proposed system. The second project exploits the vital role of iron in pathogen metabolism. The use of gallium (III), a redox inert iron (III) mimetic, to disrupt iron-dependent metabolic pathways of planktonic Pseudomonas aeruginosa (P. aeruginosa) was proposed. Bioavailability and antibacterial activity of the gallium (III) were improved with the incorporation of anionic ligands as carriers. Finally, to address the clinically relevant issue associated with biofilm infections, the third project presents an effective antibiofilm system via combinational use of antibiotics with the modified dressing. The final proposed system displayed superior antibiofilm activity against mature biofilm in in vitro and in vivo mice wound infections models. Overall, it is envisaged that the unique modes of action offered by metal ions would provide exciting prospects for refractory bacterial infections resistant to conventional antibiotics.||URI:||https://hdl.handle.net/10356/161059||DOI:||10.32657/10356/161059||Schools:||School of Chemical and Biomedical Engineering||Rights:||This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).||Fulltext Permission:||embargo_20240831||Fulltext Availability:||With Fulltext|
|Appears in Collections:||SCBE Theses|
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