Novel light-activated antimicrobial biomaterials for medical device infections

Abstract

Medical device-associated infections such as catheter-associated urinary tract infections (CAUTIs), catheter- related bloodstream infections (CRBSIs) and ventilator-associated pneumonia (VAP) remain a major global health concern. These infections arise from bacterial colonisation and biofilm formation on biomaterial surfaces, driving antimicrobial resistance (AMR). Current antimicrobial coatings, which rely on antibiotics or surface modifications, are increasingly ineffective due to resistance and limited durability. Therefore, there is an urgent need for alternative, resistance-free infection control strategies. This thesis developed light-activated antimicrobial coatings using the photosensitiser toluidine blue O (TBO) for antimicrobial photodynamic therapy (aPDT). Upon red-light irradiation, TBO adopts a catalytic approach, generating reactive oxygen species that damage a plethora of biological targets through oxidative mechanisms, causing bacterial death without promoting resistance. ‘First-generation’ polymeric coatings incorporating TBO reduced bacterial counts below the detection limit within four hours; however, regrowth occurred after 24 hours, indicating limited sustained activity under high-flow conditions due to rapid burst release of TBO. ‘Second-generation’ coatings combined TBO with hydrophobically capped silver nanoparticles (Ag-NPs) to enhance photodynamic efficacy and prolong protection. In trachea-mimetic assays, 0.5 wt% TBO coatings maintained activity against Pseudomonas aeruginosa for four days, while Ag-NPs extended protection to seven days (>7-log10 reduction). This represents the first demonstration of a light-activated antimicrobial coating capable of withstanding repeated infection challenges over seven days (the typical indwelling period for endotracheal tubes), offering a promising approach for preventing VAP. Building on these findings, ‘third-generation’ hot-melt-extruded TBO coatings incorporating a multifunctional phosphonium docusate ionic liquid ([P888 14][AOT]) improved TBO dispersion and release control. These coatings performed well under high-flow conditions, reducing Escherichia coli and Staphylococcus aureus below detection limits and sustaining antimicrobial zones for up to ten days. Collectively, this work presents innovations in light-activated antimicrobial coating design and establishes a foundation for next-generation infection-prevention strategies. 

Thesis is embargoed until 31 December 2030.

Date of Award	Dec 2025
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	Engineering and Physical Sciences Research Council
Supervisor	Colin McCoy (Supervisor) & Matthew Wylie (Supervisor)