In vivo validation of the resistance-proof activity of 2-aminoimidazole based anti-biofilm coatings for medical implants

One of the most challenging problems related to implanted medical devices is the high prevalence of biofilm-associated infections. The incidence of post-operative trauma implant infections ranges from 1% to 30%; the incidence of urinary tract infections in patients using indwelling urinary catheters ranges from 10 to 30%, contributing to 40% of all hospital-acquired infections.The persistence of the problem, and the unsatisfactory treatment outcomes, suggest that neither prophylaxis nor treatment of infection is completely effective and further improvements should be sought. Sustainable strategies, which are less prone to resistance development are hereby preferred. In previous research, we have developed covalent anti-biofilm coatings for implant substrates containing 5-aryl-2-aminoimidazole (2-AI) based anti-biofilm compounds. The 2-AIs do not kill bacteria or fungi but inhibit biofilm matrix production, as such sensitizing the microbes to antimicrobial treatment. Our evidence indicates that resistance development against 2-AIs is non-existing under in vitro conditions. In the current project, we aim at the optimization and in vivo evaluation of the anti-biofilm coatings for use on titanium (orthopedic) trauma implants and silicone rubber urinary catheters. The in vivo efficacy of trauma implants coated with the 2-AIs will be investigated in a rabbit fracture model, thereby focusing on resistance of the coated orthopedic implants to bacterial colonization as well as correct osseointegration. The in vivo efficacy of urinary catheter coatings will be evaluated in a mouse model. Combinations with both antibiotic prophylaxis and treatment regimens will be implemented and tested in our in vivo studies. Special emphasis will be on confirmation of the resistance-proof activity of 2-AI coatings under in vivo conditions, as this will create strong added value compared to alternative anti-biofilm technologies.

Keywords:medical implants

Disciplines:Plant biology