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Details of Grant 

EPSRC Reference: EP/T016124/1
Title: Exploiting bacterial virulence to trigger antimicrobial release from orthopaedic implants
Principal Investigator: Nishio Ayre, Dr WN
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Zimmer Biomet
Department: Dentistry
Organisation: Cardiff University
Scheme: New Investigator Award
Starts: 01 April 2021 Ends: 31 December 2023 Value (£): 264,217
EPSRC Research Topic Classifications:
EPSRC Industrial Sector Classifications:
Related Grants:
Panel History:
Panel DatePanel NameOutcome
27 Jan 2020 HT Investigator Led Panel January 2020 Announced
Summary on Grant Application Form
In England and Wales in 2017, 15,091 surgeries were performed due to failed hip and knee replacements. Although loosening of the implant is the main cause of failure, infection still remains a major problem, accounting for 2,865 of these procedures and over £73 million in annual costs for the NHS. This number is expected to rise with an ageing population and the number of joint replacement surgeries increasing annually.

Infected joint replacements are more complicated and costly to treat, requiring longer surgical and hospital inpatient times, and are often at a higher risk of repeated failure. This significantly affects patient quality-of-life through increased morbidity and in severe cases it can also result in amputation or death. Few commercial technologies exist to prevent this problem. Often oral or intravenous antibiotics are used; however only low concentrations reach the implant site. Coatings attempt to achieve a prolonged local release of antibiotics; however long-term exposure to antibiotics can cause toxicity issues or even encourage antibiotic resistance. Other technologies such as implant surface treatments or topographies, only slow down bacterial attachment and do not eliminate the problem entirely. There is clearly a need for smarter, more effective technologies to prevent infections in orthopaedics.

This project aims to achieve this by developing a novel smart implant coating that only releases an antimicrobial in the presence of bacteria. The concept exploits the fact that Staphylococcus aureus, a bacterium that causes joint replacement infections, releases a pore-shaped protein known as alpha-haemolysin. This protein inserts itself in cell membranes causing leakage and cell death. The implant coating consists of the same molecules as cell membranes however it contains a reservoir of antimicrobial within it. When the bacteria release alpha-haemolysin, this creates pores within the implant coating, releasing the antimicrobial and eradicating the infection locally. Three key objectives have been identified to achieve the aim of this project:

Objective 1: Optimise and characterise the coating to maximise triggered antimicrobial release.

Objective 2: Scale up the coating process and evaluate the antimicrobial activity and toxicity of the coating.

Objective 3: Evaluate the performance of the coating in a more relevant bone infection model.

Unlike existing coatings, which attempt to stimulate a response, this coating will react to the environment when bacteria are present. Using this approach, the amount of antimicrobial released will be proportional to the number of bacteria and the amount of alpha-haemolysin produced. This triggered delivery system therefore has the potential to overcome numerous issues with existing technologies. Outside of orthopaedics, this technology would have numerous applications, for example in dental and maxillofacial implants and ophthalmic and cardiovascular medical devices, where infections also pose major problems. This project also has the potential to lead to a completely new area of research, where cell and bacterial characteristics are exploited to develop smarter, more effective implant coatings and targeted drug delivery systems.
Key Findings
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Organisation Website: http://www.cf.ac.uk