The treatment of hydrocephalus often involves the placement of a shunt catheter into the cerebrospinal ventricular space, though such ventricular catheters often fail by tissue obstruction. While diverse cell types contribute to the obstruction, astrocytes are believed to contribute to late catheter failure that can occur months after shunt insertion. Using in vitro microfluidic cultures of astrocytes, we show that applied fluid shear stress leads to a decrease of cell confluency and the loss of their typical stellate cell morphology. Furthermore, we show that astrocytes exposed to moderate shear stress for an extended period of time are detached more easily upon suddenly imposed high fluid shear stress. In light of these findings and examining the range of values of wall shear stress in a typical ventricular catheter through computational fluid dynamics (CFD) simulation, we find that the typical geometry of ventricular catheters has low wall shear stress zones that can favour the growth and adhesion of astrocytes, thus promoting obstruction. Using high-precision direct flow visualization and CFD simulations, we discover that the catheter flow can be formulated as a network of Poiseuille flows. Based on this observation, we leverage a Poiseuille network model to optimize ventricular catheter design such that the distribution of wall shear stress is above a critical threshold to minimize astrocyte adhesion and growth. Using this approach, we also suggest a novel design principle that not only optimizes the wall shear stress distribution but also eliminates a stagnation zone with low wall shear stress, which is common to current ventricular catheters.

中文翻译：

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增强的壁剪切应力可防止心室导管中的星形胶质细胞阻塞

脑积水的治疗通常包括将分流导管放置到脑脊液腔内，尽管这种脑室导管经常因组织阻塞而失效。虽然不同的细胞类型会导致阻塞，但星形胶质细胞被认为会导致可能在分流器插入后数月发生的晚期导管故障。使用星形胶质细胞的体外微流体培养，我们表明施加的流体剪切应力导致细胞汇合度降低和其典型星状细胞形态的丧失。此外，我们发现星形胶质细胞长时间暴露在中等剪切应力下，在突然施加高流体剪切应力时更容易分离。根据这些发现并通过计算流体动力学 (CFD) 模拟检查典型心室导管中壁剪切应力值的范围，我们发现心室导管的典型几何形状具有低壁剪切应力区域，可以有利于生长和星形胶质细胞粘附，从而促进阻塞。使用高精度直接流可视化和 CFD 模拟，我们发现导管流可以表示为泊肃叶流网络。基于这一观察，我们利用泊肃叶网络模型来优化心室导管设计，使壁剪切应力的分布高于临界阈值，以最大限度地减少星形胶质细胞的粘附和生长。使用这种方法，