Non-thermal plasma for the control of orthopaedic infections

Abstract

This thesis aimed to evaluate the potential of non-thermal plasma (NTP) to be used for the treatment of orthopaedic infections, through a comparison of three distinct commercial NTP devices in vitro and the ability of NTP to be used as a pre-treatment for the enhancement of free and liposome-encapsulated antimicrobials against S. aureus biofilms. Furthermore, it is well established that the presence of more than one pathogen can increase the complexity of treating biofilm-associated infections, leading to an investigation into whether NTP can be used to control these, either alone or with the additional of antimicrobials.

By comparing NTP devices based on their resulting plasma physical characteristics, chemical composition, antibacterial activity and tissue tolerance, it was established that each device has desirable properties for the plasma-medicine field. Correlations between increased RONS (specifically hydrogen peroxide and nitrate) production and enhanced antibacterial activity against bacterial biofilms were established, while temperature effects of plasma exposure were found to have less influence on these outcomes. However, temperature generated at the skin surface seemed to have an influence on the penetration depth of RONS-derived from NTP in an ex vivo model, which was also correlated with the use of a conductive or non-conductive substrate.

Incorporation of vancomycin (VAN) into an optimised liposome formulation (VAN-LIPO), led to high encapsulation efficiency (81.4%), small size (101.67 nm) and cationic charge (71.63 mV) liposomes, while retaining the antibacterial activity of free vancomycin towards planktonic S. aureus. Furthermore, liposomal vancomycin (VAN-LIPO) exhibited lower cytotoxicity in RAW 264.7 macrophages and showed similar mortality rates to free VAN in an in vivo Galleria mellonella model.
Pre-treating both MSSA and MRSA biofilms with NTP produced by the J-Plasma resulted in significant decreases in MBEC values of VAN (2-fold) and VAN-LIPO (8-fold) compared to when the free drug or encapsulated drug was used alone.

Thesis is embargoed until 31 July 2030.

Date of Award	Jul 2025
Original language	English
Awarding Institution	Queen's University Belfast
Supervisor	Vicky Kett (Supervisor) & Brendan Gilmore (Supervisor)