The recent WHO report (2019) on global antimicrobial resistance (AMR) highlights not only the growing issue of resistance, identifying it as one of the greatest threats we face as a global community, but also the lack of new effective options to tackle bacterial infections. AMR costs the NHS an estimated £1 billion a year. Globally, it could cause 10 million deaths each year by 2050 and an annual economic cost of £69 trillion.
Meanwhile, the demand for orthopaedic implants has been steadily increasing worldwide due to an ageing population, the rise in obesity and a change to more active lifestyles, which is collectively leading to more osteoarthritis and degeneration of cartilage and subchondral bone in joints. In England and Wales, 187,879 primary hip and knee replacements were performed in 2015, corresponding to a rise of 46,786 since 2007. However, the number of revision hip and knee procedures also increased from 11,156 to 15,027 over the same period. The two main causes leading to implant failure and revision are aseptic loosening and infection. Current treatments of implant infections which are mostly reliant on antibiotics and silver have not been effective and developed antibacterial resistance. New anti-infective therapies are urgently needed.
Aims and Objectives
Protruding nanotopographies e.g., nanopillars on insect wings have shown to be bactericidal [1]. We have developed a range of biomimetic bactericidal nanostructures on implant materials such as titanium and investigated their unique bactericidal mechanisms [2-7]. Studies have also shown that bacteria can be inactivated with high efficiency on similar nanostructured surfaces under low electric currents [8], and electrical stimulation promotes the osteogenesis and accelerates the regeneration of bones [9]. The aim of this project is to develop synergistic therapies by combining electrical stimulation with nanotopography to combat AMR bacterial infections, while promoting the osseointegration of titanium implants.
Methodology
Firstly, bactericidal nanotopographies will be created on both flat and 3D printed titanium surface using hydrothermal etching and ion doping. Nanostructured surfaces with tunable feature sizes and conductivity will be produced. A range of analytical and microscopic techniques (XPS, XRD, Raman, SEM, TEM, AFM) will be used to characterise the nanostructured surfaces. Other physical properties e.g., wettability and conductivity will also be characterised.
Secondly, bactericidal properties of the nanostructured surfaces under electrical stimulation will be assessed by measurement of bacterial metabolic activity and viability using BacTiter-Glo Viability and Live/Dead assay for end-point analysis. Clinical pathogens associated with orthopaedic infections will be investigated, including Gram-positive Staphylococcus aureus and Staphylococcus epidermidis, and Gram-negative Escherichia coli and Pseudomonas aeruginosa. The effects of electric current and surface nanotopography on the bactericidal properties will be investigated. The bactericidal mechanisms will be elucidated.
Finally, osteogenic potential of the nanostructured surfaces under electrical stimulation will be evaluated using mesenchymal stem cells (MSC). Optimal bactericidal nanotopographies under electric currents with cytocompatibility and osteogenesis will be identified. An MSC/bacterial co-culture model will be used to investigate the synergistic effects of electrical stimulation and nanotopographies on bacterial and cellular responses.
Keywords
Antimicrobial, bactericidal, nanotopography, electric current, stem cells, osteogenesis, titanium implant
How to apply for this project
This project will be based in Bristol Dental School in the Faculty of Health Sciences at the University of Bristol.
Please visit the Faculty of Health Sciences website for details of how to apply
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