Optimising antibiotic release from medical implant to counteract biofilm formation.

Over the past 20 years, the rate of infection associated with the implantation of medical devices has reduced significantly. However, infection remains an extremely serious complication. Bacterial colonisation and biofilm formation on the implanted materials may lead to acute and chronic infection of the underlying soft tissues, notoriously difficult to treat [1]. Drugs can be administered systemically, but this has disadvantages including low drug concentration at the site and possible toxicity. Local controlled delivery of antibiotics has the potential to significantly reduce/eliminate the onset of infection.

Absolutely critical to the successful inhibition of biofilm formation is delivery of the correct amount of drug, at the optimal time, over a sustained duration - a high burst of drug could lead to toxicity, while drug concentrations must be maintained above the Minimum Inhibitory Concentration (MIC) of the infecting bacteria, as long-term exposure is linked with resistance [1]. In the absence of a detailed understanding of the mechanisms governing antibiotic release kinetics and bacterial colonisation, it is extremely difficult to determine what the optimal drug release strategy should be.
The biofilms that form are known to be highly complex structures. They are usually heterogeneous, suggesting that transport of nutrients and drug within the biofilm will be anisotropic [2], with this anisotropy depending on the evolving structure.

This project will initially focus on building models corresponding to a simplified in-vitro setting, where some experimental data is available, including antibiotic release profiles from different types of implant coating as well as corresponding bacterial inhibition data. Beyond modelling the in-vitro situation, specific implants (e.g. orthopaedic or vascular implants) and the corresponding in-vivo environment will be considered. This is likely to include modelling the influence of spatiotemporally varying mechanical and chemical cues (biological fluid flows, nutrient supplies) on the biofilm formation and response to treatment with antibiotic. Of particular interest is how the anisotropy of internal and external forces is 'imprinted' on the biofilm as it grows. Developing models of biofilm formation subject to drug delivery in this way will develop understanding of the interplay between the two processes and then explore possible optimal drug delivery strategies.

[1] C.R. Arciola, D. Campoccia and L. Montanaro (2018) Implant infections: adhesion, biofilm formation and immune evasion. Nature Reviews Microbiology 16: 397-409
[2] A.S. Van Wey et al. (2011) Anisotropic nutrient transport in three-dimensional single-species bacter