EngSci- ELM-372 : Multifunctional agents for ultrasound-mediated treatment of biofilms in chronic infections

University of Southampton

Chronic wounds, such as diabetic foot ulcers (DUFs), are characterised by slow healing rates with high risks of bacterial infection. Notably, ulceration and amputation from DFUs cost the NHS ~£650 million per year and tremendously compromise a patient’s quality of life. The formation of bacterial biofilms in the wound bed significantly impacts on healing times, since multiple bacterial species reside within these biofilms, including pathogens having multiple drug resistance (MDR). Researchers at Public Health England have established complex biofilm models based on MDR species found in different chronic wound types, and have demonstrated that the efficacy of antimicrobial compounds is much reduced in complex environments, even for bacteria which are usually susceptible to treatment.

The potential of exogenous nitric oxide (NO) to act as a signal for the dispersal of bacterial biofilms has attracted considerable interest. Notably, exposure of biofilms to NO may reduce their resistance to antibiotics, and treatments combining NO and antimicrobial compounds may effectively control the progression of biofilm-related infections.

In this study, we will develop ultrasound-responsive agents designed to act as carriers for both nitric oxide and antibiotics. Agents will be engineered to synergistically deliver NO and antimicrobial compounds upon ultrasound stimulation, in a spatially- and temporally-controlled fashion. Their response to ultrasound waves will also impart local mechanical stress, which is expected to significantly increase penetration efficiency of bioactive compounds across the biofilm matrix. We anticipate that these multifunctional agents will provide a powerful treatment modality for biofilm-related MDR chronic infections.

To this end, the PhD candidate will utilise both experimental and computational techniques to (i) engineer ultrasound-responsive agents capable of co-transporting nitric oxide and antimicrobial compounds; (ii) identify ultrasound exposure regimes to deliver the therapeutic payload at desired time-points for treatment, and enhance its penetration across the biofilm matrix; and (iii) validate agents’ therapeutic potential against conventional treatments, using complex models of chronic infections.

This PhD programme offers a unique opportunity to work in a multi-disciplinary environment based at a world-class research centre, with shared support from the Faculties of Engineering and the Environment and Biological Sciences at the University of Southampton. The PhD candidate will work closely with partners at Public Health England, and will have the unique opportunity to develop expertise in cutting-edge technologies for the production of ultrasound-responsive agents, ultrasound-based therapies, and microbiological modelling of infections.

The ideal candidate will have a solid background in bio-physics or biomedical, acoustical or mechanical engineering.

If you wish to discuss any details of the project informally, please contact Dr Dario Carugo (Bioengineering Science research group, Email: D.Carugo@soton.ac.uk, Tel: +44 (0) 2380 59 3242) or Prof Jeremy Webb (Environmental Biosciences research group, Email: J.S.Webb@soton.ac.uk, Tel: +44 (0) 2380 59 4390).

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South East England