Development of bioactive ultrasound-responsive coatings for the prevention and treatment of orthopaedic implant-related infections
LEAD SUPERVISOR: Dr Dario Carugo, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences
Co-supervisor: Dr Malavika Nair, Department of Engineering Science
Co-supervisor: Dr Simon Abram, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences
Commercial partner: Adler Ortho®
Implant-related orthopaedic infections pose a very significant burden on patients and healthcare systems globally. These infections are difficult to treat and are widely regarded as a devasting complication in orthopaedic surgery. They often occur because bacteria readily form a “biofilm” on the surfaces of orthopaedic implants, such as joint replacements. Biofilms can be described as aggregations of microorganisms in a heterogeneous community, embedded in a matrix of extracellular polymeric substances that provides a physical and bio-chemical barrier to both endogenous and exogenous stimuli. Once established, biofilms are extremely difficult to eradicate without revision surgery to remove the infected implants. Moreover, they feature both inherited genetic resistance and an innate tolerance to traditional antibiotics, making them a prevalent and growing concern for public health. Novel implant coatings with antibacterial and antibiofilm performance would therefore have significant potential to revolutionise prevention and treatment of orthopaedic implant-related infections.
In previous research, we demonstrated that ultrasound-responsive agents (e.g., in the form of nano- and micro-particulate systems) are effective in physically disrupting bacterial biofilms grown on different surface types, as well as in enhancing the bactericidal effects of antibiotic compounds. We have also shown that the combined application of ultrasound-responsive agents and reactive oxygen species (such as nitric oxide) can further potentiate the effect of antibiotics. Despite these ultrasound-mediated approaches have shown great potential as a treatment modality against biofilm infections, their application in the context of orthopaedic implants remains largely unexplored.
This project aims to address this research gap by developing innovative ultrasound-responsive coatings and investigate their applicability as a preventative and/or treatment strategy against implant-related biofilm infections. The project will be structured into three inter-linked objectives: (Objective 1) formulation and characterisation of ultrasound-responsive surface coatings, where we will specifically explore two types of coating approaches. The first group will include coatings incorporating ultrasound-responsive moieties or agents, which can be remotely activated to release an antibiotic compound in situ as well as to perturb biofilms mechanically. The second group will comprise coatings with piezoelectric properties; i.e., capable of transducing an extracorporeally applied ultrasound stimulus into a local electrical signal that may prevent bacterial adhesion and/or interfere with biofilm growth. (Objective 2) In-vitro screening of the efficacy of different coating formulations, in terms of their ability to prevent bacterial cell adhesion, biofilm formation and growth, as well as for potential cytotoxic effects on peri-implant tissues. Coatings will be bio-printed on small-scale implant prototypes for analysis within a ‘implant-on-a-chip’ platform and exposed to patient-derived bacterial species. (3) The best performing coating candidates will be applied onto full-scale implant prototypes, and characterised for their physical and chemical stability, mechanical performance, and antibiofilm efficacy.
The student will work closely with the industrial partner Adler Ortho, with expertise in 3D printing and additive manufacturing applied to orthopaedic implants.