Minimising infection risk of implantable titanium

Britton, Savannah

Abstract

The use of antibacterial coatings on bone biomaterial has attracted interest from various fields such as orthopaedics, dentistry and veterinary medicine. However, the process of attaching suitable compounds to biomaterial surfaces in a stable manner presents a significant challenge. One pragmatic approach is to utilise approved antibiotics that have been shown to remain effective when immobilised. One such antibiotic is teicoplanin (Teic), a glycopeptide that was discovered in the 1990s to be useful as a chiral selector in chromatographic enantiomeric separations. Importantly, Teic works at the level of the bacterial cell wall making it a potential candidate for biomaterial functionalisations. Intial investigations attempted to functionalise titanium (Ti) with polydopamine and use this platform to capture Teic. However, Teic was found to have a natural affinity for the oxide layer of Ti. Whilst Teic demonstrated a robust adsorption to Ti, it was found that the presence of phosphate compromised this interaction, resulting in the antibiotic eluting from the oxide. Before attempting to covalently attach the Teic to Ti, a commercially available Teic stationary phase was exposed to S. aureus to evaluate its antibacterial capabilities. Unfortunately, it was found that the Teic stationary phase had no impact on the viability of S. aureus, despite its ability to bind to N-Acetyl-L-Lys-D-Ala-D-Ala, indicating that covalent attachment of the glycopeptide antibiotic to a biomaterial surface does not result in the generation of an antibacterial surface. Yet, as expected, Teic has consistently displayed great antibacterial activity and was also able to enhance the maturation of osteoblasts and so work moved toward controlling the elution of Teic by encapsulating the antibiotic in a composite hydrogel made from chitosan and gelatin and crosslinking with genipin. This composite hydrogel scaffold demonstrated a sustained release of Teic over the course of a week and the same observations were made when the hydrogel was injected into a cancellous bone model, demonstrating the potential of this composite scaffold in reducing the incidence of periprosthetic joint infection (PJI). Overall, this thesis has demonstrated the potential of using Teic in orthopaedic applications but has also highlighted the difficulty in generating a stable, Teic-coated Ti surface finish.

• Thesis Type: Thesis
• Deposit Date: May 15, 2023
• Publicly Available Date: Dec 13, 2023
• Public URL: https://uwe-repository.worktribe.com/output/10791885
• Award Date: Dec 13, 2023