The design, development, and testing of novel next generation in vitro agar-based urethral models for medical device innovation

Abstract

Catheters are one of the most utilised medical devices in modern medicine with catheter associated urinary tract infections (CAUTI) being ubiquitous in worldwide healthcare settings. These infections negatively affect patient mortality and morbidity as well as providing reservoirs for the proliferation of antimicrobial resistant genes in culpable strains. The aim of this study was to develop a novel, robust and reproducible, in vitro urethra model that can aid in the development and testing of next generation urological devices; with a specific interest in testing the efficacy of intermittent catheters to prevent friction-mediated bacterial displacement and assessing indwelling catheters for the prevention of extraluminal bacterial migration. The base in vitro urethra model comprised of multiple preformed channels within a chromogenic agar-based matrix. The base model was then modified. A novel in vitro urethra friction model was designed to study friction-mediated bacterial displacement during intermittent catheter insertion. A novel in vitro urethra diffusion model was developed to assess the diffusion of antimicrobial compounds from a novel polymer coating in the three dimensional space of the urethra. A novel in vitro urethra extraluminal migration model was devised to visualise bacterial migration on the outer surfaces of a catheter during long term placement. The design and development process for each model, and associated methodology, was long and at times arduous. The in vitro urethra friction and extraluminal migration models were both validated with E. coli and S. aureus through twelve independent tests each and were found to be highly reproducible (P ≥ 0.265 and P ≥ 0.851, respectively). The development and findings of these models have been disseminated at international conferences and submitted/published in peer review journals. The novel in vitro urethra friction model directly influenced IP protected changes in the design of a novel friction-eliminating intermittent catheter, developed by the industry partner of this study. The novel in vitro urethra extraluminal migration model guided the IP protected redesign of an antimicrobial coated catheter, developed by the industry partner of this study, to reduce the antimicrobial coating by ≥50% without reducing its antimicrobial efficacy. Unfortunately, the novel in vitro urethra diffusion model development did not reach fruition as the needs and the overall aims of the project evolved, it still presents a novel idea that could prove useful in other future studies. Whilst the knowledge of this thesis could have been IP protected, it was openly published in the interest of public health to allow uninhibited innovation in urological medicine. Innovation in the field of urological medical devices has been long overdue with little changes in the basic function and design of catheters since the early 20th century. Healthcare-associated infections and in particular CAUTIs are contributing to the global overuse of antibiotics and the looming problem of antibiotic resistance. The novel in vitro urethra models described herein, have the potential to inspire change in the medical device industry’s design of urinary catheters and strategies for CAUTI prevention.