Development and in vivo validation of a novel triggered release antibiofilm coating for orthopaedic implants and vascular grafts.

Interventions

Therapeutics

Research Project: 2023-06-01 - 2026-05-31
Total sum awarded: €798 571

Implant-related infections are typically caused by biofilms, which increase the tolerance to antimicrobials and increase the risk for treatment failure. The TRA-COAT project aims to reduce the incidence of implant infections by developing a novel, resistance-proof antimicrobial coating with innovative functionalities, including biofilm preventing activity and triggered localized release of classic antimicrobials. The focus will be on trauma implants and vascular grafts, with potential translation to many other implants. The coating will consist of a polydopamine layer in combination with a covalently bonded 2-aminoimidazole-based biofilm inhibitor and a reversibly bonded classic antimicrobial. The action of the inhibitor will reduce the biofilm matrix production which would otherwise prevent the immune system to clear the microorganisms. If biofilm should still remain, growth of the bacteria on the surface of the implant will locally decrease the pH and trigger the release of the antimicrobial, killing the pathogens. The coating is designed to provide a resistance-proof alternative for systemic antibiotic treatment: (i) the biofilm inhibitors are intrinsically robust to resistance evolution due to their ‘public good’ targeting character. (ii) Due to the biofilm inhibition, the classic antimicrobial will be more effective, as such reducing the risk for resistance development against this antimicrobial. (iii) Limiting the use of antimicrobial to local on-demand release further reduces the risk of resistance development and off target effects e.g. on the host microbiome.

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  • Hans Steenackers, Katholieke Universiteit Leuven, Belgium (Coordinator)
  • Stephan Zeiter, AO Research Institute Davos, Switzerland (Partner)
  • Annette Moter, Charité University Medicine, Germany (Partner)

One of the most challenging problems related to implanted medical devices is the high prevalence of microbial infections. Previous studies showed that implant-related infections are typically caused by biofilm forming microbes. In contrast to infections caused by free-floating microbes, biofilms generally increase the tolerance to antimicrobials and increase the risk for antimicrobial resistance development. The TRA-COAT project aims to address the incidence of implant infections by developing a novel, resistance-proof antimicrobial coating with innovative functionalities, including anti-biofilm activity and triggered release of classic antimicrobials. The focus will be on orthopaedic trauma implants and vascular grafts, but can later be applied to other implants. The coating will combine a covalently bonded biofilm inhibitor and a reversibly bonded classic antimicrobial. The action of the inhibitor will reduce the slimy matrix production during biofilm formation which will allow the immune system to better remove the microorganisms. If remaining biofilm should still occur, growth of the bacteria on the surface will locally trigger release of the antimicrobial, killing the pathogens. The coating is designed to be resistance-proof. Indeed, the biofilm inhibitors are intrinsically robust to resistance and will enhance the effectivity against the classic antimicrobial, as such also reducing the risk for resistance against the latter. The local and time-restricted release of the antimicrobial will moreover further reduce the risk of resistance development.