In vitro evaluation of novel surface modifying molecules to prevent bacterial adhesion to urological devices
Christopher Munday1,2,3,4, Alexandra Piotrowicz5, Kyle MacDonald1,2,5, Antonio Cillero5, Jeannette Ho5, John Denstedt1,3 Jeremy P. Burton1,2,3,4
1 Lawson Health Research Institute, London, Canada
2 Canadian Centre for Human Microbiome and Probiotics, London, Canada
3 Division of Urology, Department of Surgery, Schulich School of Medicine, University of Western Ontario, London, Canada
4 Department of Microbiology & Immunology, University of Western Ontario, London, Canada
5 Interface Biologics, Toronto, Canada
Bacterial adhesion and biofilm formation on urological devices such as stents and catheters is an undesirable phenomena that can lead to device-related infection and other co-morbidities. A range of potential technologies utilizing both passive mechanisms and active antimicrobials have been developed to combat this issue, but clinical efficacy remains limited. The objective of this study was to investigate the ability of a novel passive surface modification technology using fluorinated surface modifying molecules (SMMs) to address this clinical need.
Polyurethane control and SMM-modified prototypes for testing (rods or catheter tubing) were prepared using standard melt extrusion processes. X-ray photoelectron spectroscopy confirmed the presence of SMM at device surfaces. Efficacy of devices to resist bacterial adhesion was assessed using both static and flow models. Static experiments consisted of sample incubation in bacterial inoculum followed by sonication to detach adhered bacteria and quantification by plate counts. Flow experiments were conducted using a custom circulating flow system with artificial urine.
SMM-modified prototypes showed up to 2 log lower microbial adhesion compared to unmodified controls after 2h incubation in buffer inoculated with various gram positive, gram negative bacteria or yeast. The anti-adhesive property of SMM prototypes was confirmed in both artificial and human urine with three uropathogens (E. coli, E. faecalis, P. mirabilis), as well as in clinical urine samples from patients with ureteral stents, where SMM modified samples showed reduced attachment of mixed bacterial populations after 24h of incubation. Experiments under flow demonstrated potential of SMM modified surfaces to resist adhesion in dynamic environments and for extended time frames, with 5 log lower attachment of E. coli observed on SMM-modified tubing vs controls at both 1 and 3 days post inoculation. Corresponding reductions in biofilm formation were confirmed with crystal violet staining and scanning electron microscopy.
Modification of urological devices with SMMs may be an effective strategy to reduce bacterial adhesion and biofilm formation. The passive nature of the SMMs is advantageous as it provides a stable surface not subject to depletion or de-activation of the functional entity over time, as may be the case for surfaces modified with eluting or active antimicrobials.