Resorbable antibacterial coatings for orthopaedic implants

Description of the project

Bacterial infections associated with orthopaedic implants are complex to treat and can result in severe complications for patients. Bacterial cells often form a “biofilm” on the surface of orthopaedic implants, whereby bacterial cells are embedded within a matrix of polysaccharides, proteins, extracellular DNA, and lipids¹. This extracellular matrix provides a physical and chemical barrier to external physical and chemical stimuli, such as antibiotic compounds, or to endogenous biological stimuli. Since biofilms are extremely difficult to eradicate, patients have to undergo revision surgery in many cases. There is therefore a growing need to develop innovative strategies to address bacterial adhesion and biofilm formation on orthopaedic implants. This project will specifically investigate the development of surface coatings with anti-biofilm performance that may prevent and/or treat orthopaedic implant-related infections. 

The student will develop different classes of resorbable coatings, evaluate their anti-biofilm performance as well as applicability onto orthopaedic implants. The project will be structured into three main objectives: (1) formulation/characterisation of resorbable and biocompatible surface coatings, with a particular focus on the ideal rates of degradation to prevent bacterial adhesion and biofilm formation. Coatings evaluated may also incorporate antibiotic drugs or stimuli-responsive moieties^2,3 for enhanced antibacterial efficacy. (2) Evaluation of the antimicrobial performance of different coating formulations, in terms of their ability to prevent bacterial cell adhesion, biofilm formation and growth, as well as for cytotoxicity. Efficacy will be evaluated using rapidly prototyped, laboratory-scale models that will be manufactured in-house using 3D- and bio-printing. (3) The most promising coatings will then be applied onto full-scale implants, and further characterised for their physical and biological performance. 

Keywords

Biofilms, orthopaedic implants, coatings, ultrasound, bio-printing

Relevant publications

[1] D. Ronin et al., Current and novel diagnostics for orthopedic implant biofilm infections: a review, Journal of Pathology, Microbiology and Immunology, 130, 59:81, 2021 (link).

[2] G. LuTheryn et al., Bactericidal and anti-biofilm effects of uncharged and cationic ultrasound-responsive nitric oxide microbubbles on Pseudomonas aeruginosa biofilms, Front. Cell. Infect. Microbiol., 12, 2022 (link)

[3] F. Plazonic et al., Bactericidal Effect of Ultrasound-Responsive Microbubbles and Sub-inhibitory Gentamicin against Pseudomonas aeruginosa Biofilms on Substrates With Differing Acoustic Impedance, Ultrasound in Medicine and Biology, 48, 1888-1898, 2022 (link) 

Training and support available

Training The Botnar Research Centre plays host to the University of Oxford's Institute of Musculoskeletal Sciences, which enables and encourages research and education into the causes of musculoskeletal disease and their treatment. Training will be provided in techniques including: (i) computational methods (FEM, CAD) for implant design, and fabrication techniques for implants and surface coatings (such as 3D additive manufacturing and bio-printing); (ii) material characterisation techniques, such as scanning electron microscopy and optical profilometry; (iii) bacterial/mammalian cell culturing, immunofluorescent microscopy, immunohistological assays, bacterial/biofilm viability assays; and (iv) operation of biomedical ultrasound instrumentation and formulation of ultrasound-responsive agents.

A core curriculum of lectures will be taken in the first term to provide a solid foundation in a broad range of subjects including musculoskeletal biology, inflammation, epigenetics, translational immunology, data analysis and the microbiome. Students will also be required to attend regular seminars within the Department and those relevant in the wider University.

Students will be expected to present data regularly in Departmental seminars, attend the Bio-Engineering and Bio-Materials Division regular group meetings, and to attend external conferences to present their research globally, with limited financial support from the Department.

Students will also have the opportunity to work in the Bio-Engineering and Bio-Materials Division in the Botnar Research Centre, which is a highly interdisciplinary and collaborative environment bringing together a team of >7 PIs across NDORMS and Engineering, with several PhD students and postdoctoral researchers, working at the interface between engineering, biology, and pharmaceutics. The Laboratories are equipped with state-of-the-art and advanced instrumentation for particle formulation and characterisation, bio-printing and 3D printing, biomedical ultrasound, cell and bacterial culturing, and confocal microscopy. They will also work very closely with co-supervisors and collaborators based at the Nuffield Orthopaedic Centre (Oxford University Hospitals).

Students will have access to various courses run by the Medical Sciences Division Skills Training Team and other Departments. All students are required to attend a 2-day Statistical and Experimental Design course at NDORMS and run by the IT department (information will be provided once accepted to the programme).

How to Apply

It is recommended that, in the first instance, you contact the relevant supervisor(s) and the Graduate Studies Office (graduate.studies@ndorms.ox.ac.uk), who will be able to advise you of the essential requirements.

Interested applicants should have, or expect to obtain, a first or upper second-class BSc degree or equivalent in a relevant subject and will also need to provide evidence of English language competence (where applicable). The application guide and form are found online and the D.Phil will commence in October 2024.

Applications should be made to one of the following programmes using the specified course code.

D.Phil in Molecular and Cellular Medicine (course code: RD_MP1)

DPhil in Musculoskeletal Sciences (course code: RD_ML2) 

For further information, please visit http://www.ox.ac.uk/admissions/graduate/applying-to-oxford.