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

Abstract

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.

Keywords: animal models; design; encrustation; evaluation; ex vivo; in vitro; in vivo; material; urinary stent; urinary tract models.

Figure A1

PRISMA flow algorithm; search of databases: PubMed, Scopus, Web of Science. Keywords: in vitro, encrustation, artificial urine, ureteral, urethral, stent, catheter, in combination with Boolean operators; time period until 2021. Exclusion criteria: non-relevant, non-English articles, no abstract available, non-full-text.

Figure A2

PRISMA flow algorithm; search of databases: PubMed, Scopus, Web of Science. Keywords: stent, design, material, encrustation, biodegradable, ex vivo, ureter, urinary tract models; time period until 2021. Exclusion criteria: non relevant or not meeting objective of our study or not ex vivo, non-English or non-Spanish articles, no abstract available, non-full-text.

Figure A3

PRISMA flow algorithm; search of databases: PubMed, Scopus, Web of Science. Keywords: validation; testing; urinary stent; ureteral stent; urethral stent; animal model; in vivo; time period until 2021. Exclusion criteria: non-relevant, not in vivo, non-English, no abstract available, non-full-text.

Figure 1

Bioreactor Labfors 5.

Figure 2

Flow modeling.

Figure 3

Navier–Stokes equations to investigate the movement of urine within the ureter. Legend: v = spatial velocity vector; ρ = fluid density; p = static pressure; μ = dynamic viscosity; f = body force vector.

Figure 4

Retrograde ureteropyelography of a porcine left nephroureteral unit.