Antibacterial coating via hybrid Layer-by-Layer deposition system for fighting infections in orthopaedic implants

Newcastle University Senior Lecturers in Bioengineering, Dr Ana Ferreira-Duarte and Dr Piergiorgio Gentile, are recipients of Orthopaedic Research UK’s Early Careers Research funding. They are developing an antibacterial coating for metallic orthopaedic implants to help fight against infections.

The incidence of nosocomial surgical infections on orthopaedic implants may range from 0.5 to 10% for non-exposed bone fractures and can go up to 50% in open or exposed fractures. Infections may be treated with antibiotics, but some people are resistant to antibiotics, and the antibiotics cannot penetrate through the biofilm to mitigate or address the infection as it spreads across the body. Infections in orthopaedic implants pose life-threatening consequences. ‘They are very, very painful and have high associated costs in clinical management,’ said Ferreira-Duarte.

Ferreira-Duarte explained, ‘The solution is removing the implant and trying to control the infection through a strong treatment of antibiotics.’ ‘There are some approaches in the implants, such as modifying the roughness or playing with the implant’s properties to try to stop bacteria from attaching. But these impact how well the tissue will grow on the implant and how it integrates with the surrounding tissue.

With partner company Zimmer-Biomet, we developed and patented a unique machine for coatings with layer-by-layer assembly. We can diversify the materials, minimise waste and control the coating’s properties better. We deposit oppositely charged materials on the surface of the orthopaedic implants and can apply these methods in two ways: spray coating or dipping. There is no existing equipment which allows you to do both.

‘Dipping the implant in the polyelectrolytes to completely coat facilitates a more stable and homogeneous coating. However, this requires liquid enough to coat the entire implant, with limitations that some molecules are expensive or unsuitable for dipping. Spray is quicker than dipping, requires less material and therefore is cheaper. But because spray deposition is quicker, it doesn’t allow the deposited molecules to organise and form a stable coating. We combine these two technologies, providing the best of the two.’

‘In vitro, we managed to create a stable coating on the orthopaedic implants. The tests are promising, in terms of promoting new bone formation while minimising the attachment of the bacteria and preventing biofilm formation on the implants.’

‘The hybrid technology allows us to minimise the waste of the polyelectrolytes and bioactive molecules. We also work on minimising the manufacturing carbon footprint and the amount of materials and waste. The water-based solutions used in this process are non-toxic.’

Reflections

‘The project offered an opportunity for the postdoctoral fellow to work on a multidisciplinary project, interfacing directly with companies and clinicians. In our team, we have orthopaedic clinicians, microbiologists, and biomedical engineers with a background in mechanical or chemical engineering.  We received feedback on regulations from the industry team of scientists, researchers, and business development managers within Zimmer Biomet. Clinicians provided feedback on the clinical needs and suitable approaches, and the microbiologists on infections and biofilm formation.’

‘During our discussions, we talked about how this technology could be useful for various patient communities, not only musculoskeletal but also cancer patients who need treatments delivering therapeutic drugs and biomolecules. We had the opportunity to run some patient and public Involvement (PPI) events with Voice Global, an international network of citizens at Newcastle University, to harness ideas and showcase our project goal and results of our project to the public. We were very pleased about the outcome of that meeting because the feedback on our work was positive and with potential impact on patients affected by implant infections.’

‘Without the funding, we would not have done this research or discovered all the advantages this technology has. At the moment, there is no solution to these implant infections and the problem is increasing. This funding allows us to explore alternatives which can improve the osseointegration and the properties of the implant and minimise that risk of infection.’

Long-term goals

‘Regulations for orthopaedic implants are quite rigorous and challenging. As robust and reliable data is needed to meet the requirements demanded to create safe implant coatings that can be used later in patients. So we need to perform further tests closer to the clinical environment supported by robust in vitro tests to assess the immune response.’

‘In the next ten years, we envisage this technology at a higher Technology readiness level (TRL) and adopted by the research and industry community. We would like to involve more patients, clinicians, policymakers, and regulators and try to make the technologies more efficient. Hopefully, we will be closer to the clinical theatre.’

‘We have learned so much from the patients and public, our partner company, and surgeons. We want to move into the next stage of the project, which is trying to create a smarter coating and implant, working with Zimmer-Biomet to implement these in their portfolio.’