Urinary Stent Development and Evaluation Models: In Vitro, Ex Vivo and In Vivo-A European Network of Multidisciplinary Research to Improve Urinary Stents (ENIUS) Initiative.

Background: When trying to modify urinary stents, certain pre-clinical steps have to be followed before clinical evaluation in humans. Usually, the process starts as an in silico assessment. The urinary tract is a highly complex, dynamic and variable environment, which makes a computer simulation closely reflecting physiological conditions extremely challenging. Therefore, the pre-clinical evaluation needs to go through further steps of in vitro, ex vivo and in vivo assessments. Methods and materials: Within the European Network of Multidisciplinary Research to Improve Urinary Stents (ENIUS), the authors summarized and evaluated stent assessment models in silico, in vitro, ex vivo and in vivo. The topic and relevant sub-topics were researched in a systematic literature search in Embase, Scope, Web of Science and PubMed. Clinicaltrials.gov was consulted for ongoing trials. Articles were selected systematically according to guidelines with non-relevant, non-complete, and non-English or Spanish language articles excluded. Results: In the first part of this paper, we critically evaluate in vitro stent assessment models used over the last five decades, outlining briefly their strengths and weaknesses. In the second part, we provide a step-by-step guide on what to consider when setting up an ex vivo model for stent evaluation on the example of a biodegradable stent. Lastly, the third part lists and discusses the pros and cons of available animal models for urinary stent evaluation, this being the final step before human trials. Conclusions: We hope that this overview can provide a practical guide and a critical discussion of the experimental pre-clinical evaluation steps needed, which will help interested readers in choosing the right methodology from the start of a stent evaluation process once an in silico assessment has been completed. Only a transparent multidisciplinary approach using the correct methodology will lead to a successful clinical implementation of any new or modified stent.

A biomimetic urethral model to evaluate urinary catheter lubricity and epithelial micro-trauma.

The standard method of evaluating the lubricity of intermittent urinary catheters with coefficient of friction (CoF) testing is not physiologically relevant, while there is also a dearth of published research on catheter-associated urethral micro-trauma. We developed a novel human urethral epithelial cell-seeded model of the urethra to replace the rubber counter-surface used in standard CoF testing. This cell-seeded model, in conjunction with a novel testing device, allows an investigation of catheter-associated epithelial micro-trauma in vitro for the first time. The CoF of four brands of commercially-available hydrophilic-coated intermittent catheters was measured using both the rubber and urethral model counter-surfaces. Post-catheterisation of the urethral model, the damage to the epithelial layer was analysed using standard cell imaging. The rubber counter-surface was shown to over-estimate the CoF of gel-coated catheters compared to our urethral model due to stick-slip behaviour caused by polymer-on-polymer interaction of the catheter base material on the rubber counter-surface. We identified no deleterious effect due to the presence or design of catheter eyelets to either the CoF measurements or the degree of epithelium damage in our model. Furthermore, the epithelial damage did not correlate with the measured CoF of the low friction catheters, suggesting a more nuanced pathogenesis of urethral irritation and casting doubt on the translatability of a solely mechanical assessment of lubricity of urinary catheters to a clinical effect.