De Grazia Antonio, LuTheryn Gareth, Meghdadi Alireza, Mosayyebi Ali, Espinosa-Ortiz Erika J, Gerlach Robin, Carugo Dario
Bioengineering Science Research Group, Faculty of Engineering and Physical Sciences, University of Southampton, Southampton SO17 1BJ, UK.
Institute for Life Sciences (IfLS), University of Southampton, Southampton SO17 1BJ, UK.
Micromachines (Basel). 2020 Apr 13;11(4):408. doi: 10.3390/mi11040408.
Obstructions of the ureter lumen can originate from intrinsic or extrinsic factors, such as kidney stones, tumours, or strictures. These can affect the physiological flow of urine from the kidneys to the bladder, potentially causing infection, pain, and kidney failure. To overcome these complications, ureteral stents are often deployed clinically in order to temporarily re-establish urinary flow. Despite their clinical benefits, stents are prone to encrustation and biofilm formation that lead to reduced quality of life for patients; however, the mechanisms underlying the formation of crystalline biofilms in stents are not yet fully understood. In this study, we developed microfluidic-based devices replicating the urodynamic field within different configurations of an occluded and stented ureter. We employed computational fluid dynamic simulations to characterise the flow dynamic field within these models and investigated bacterial attachment ( ) by means of crystal violet staining and fluorescence microscopy. We identified the presence of hydrodynamic cavities in the vicinity of a ureteric occlusion, which were characterised by low levels of wall shear stress (WSS < 40 mPa), and observed that initiation of bacterial attachment occurred in these specific regions of the stented ureter. Notably, the bacterial coverage area was directly proportional to the number of cavities present in the model. Fluorescence microscopy confirmed that the number density of bacteria was greater within cavities (3 bacteria·mm) when compared to side-holes of the stent (1 bacterium·mm) or its luminal surface (0.12·bacteria mm). These findings informed the design of a novel technological solution against bacterial attachment, which reduces the extent of cavity flow and increases wall shear stress over the stent's surface.
输尿管管腔梗阻可源于内在或外在因素，如肾结石、肿瘤或狭窄。这些因素会影响尿液从肾脏到膀胱的生理流动，可能导致感染、疼痛和肾衰竭。为克服这些并发症，临床上常置入输尿管支架以暂时恢复尿流。尽管支架具有临床益处，但它们易于结垢和形成生物膜，从而导致患者生活质量下降；然而，支架中结晶生物膜形成的潜在机制尚未完全明确。在本研究中，我们开发了基于微流控的装置，以复制不同构型的梗阻和置入支架的输尿管内的尿动力学场。我们采用计算流体动力学模拟来表征这些模型内的流动动力学场，并通过结晶紫染色和荧光显微镜研究细菌附着情况。我们发现在输尿管梗阻附近存在流体动力学腔，其特征是壁面剪应力水平较低（WSS < 40 mPa），并观察到细菌附着起始发生在置入支架输尿管的这些特定区域。值得注意的是，细菌覆盖面积与模型中存在的腔的数量成正比。荧光显微镜证实，与支架侧孔（1个细菌·mm）或其管腔表面（0.12个细菌·mm）相比，腔内细菌数密度更高（3个细菌·mm）。这些发现为一种新型抗细菌附着技术解决方案的设计提供了依据，该方案可减少腔流程度并增加支架表面的壁面剪应力。
