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Title: Mechanisms of encrustation within ureteral stents
Author: Mosayyebi, Ali
ISNI:       0000 0004 7960 6899
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2018
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Ureteric obstructions due to intrinsic or extrinsic causes (e.g., stones, tumours, and fibrosis) can impair urine flow, resulting in pain, urinary tract infection, and kidney damage. Ureteral stenting is one of the most effective and least invasive clinical procedures for restoring urine drainage in the occluded ureter. A ureteric stent is a hollow tube with side-holes, which allows the urine to bypass the source of obstruction. Despite their clinical success, stents often suffer from failures and side effects that impact on both patient's quality of life and costs for national health services. One of the most common complications is encrustation of the stent's surface caused by calcifications, and particularly of side-holes, which are essential for maintaining urine drainage. Despite efforts have been devoted to develop novel materials and stent coatings; encrustation still remains a major complication. Few studies have however suggested that flow dynamics can potentially govern formation and deposition of encrusting crystals; however, improvements to the flow performance of stents are hindered by a lack of quantitative correlation between flow and encrustation processes. This study aims to develop a novel ureteric stent architecture, which flow performance is designed to reduce encrustation rates. In a first step of the study, a correlation between flow metrics - specifically wall shear stress (WSS) - and the accumulation of encrusting particles in stents was investigated. For this purpose, microfluidic-based models of the occluded and stented ureter (referred to as 'stent-on-chip' models) were developed, replicating the complexity of the WSS field at key hydrodynamic regions of interest (such as side-holes of the stent and the cavity formed by a ureteric occlusion). Using this model, a robust and inverse correlation between WSS and size/growth rate of encrusting deposits was demonstrated. Critical regions suffering from low WSS, and thus prone to faster encrustation, were also identified. These included holes that did not experience flow exchange between the stent and the ureter (referred to as 'inactive' holes), and the occluded cavity. The presence of these critical regions was also verified at a full-scale, both experimentally and numerically, to further validate the ability of microfluidic-based models to replicate relevant flow domains of a stented ureter. Stent-on-chip models were then employed as a technology platform to screen the effect of changing different architectural features of the stent. Changes to the thickness and shape of the side-holes were investigated, with a focus on those alterations that could be easily implemented within industrial constraints. A novel stent design, combining optimal thickness and a triangular hole shape, was developed; it showed significantly lower encrustation rates when compared to a standard stent design. Finally, a fabrication method was developed and validated for fabricating triangular side holes on a commercial ureteric stent. The developed stent design and fabrication method are easy-to-implement and thus the novel stent prototype can be potentially employed as an adjuvant approach to existing material and surface coatings against encrustation. Future pre-clinical investigations are required to evaluate the potential clinical benefit of the proposed stent design.
Supervisor: Carugo, Dario Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available