In the tumor environment, interstitial pressure drives interstitial flow drainage from the tumor core to the lymphatic vessels. Recent studies have highlighted the key role of interstitial pressure in tumor development and cell migration. High intratumoral pressures, up to 60 mm Hg , have been reported in cancer patients. In a previous study, we showed that such pressure levels induce fracture in an experimental tumor model consisting of a microfluidic system holding a cellular aggregate. Here, we investigate and quantify the characteristics of tumor model fracture under a range of flow conditions. Our findings suggest a strong dependence of viscoelastic fracture behavior on the loading rate exerted by flow. The aggregate exhibits fragile fracture at high loading rates and ductile fracture at lower rates. The loading rate also modifies the permeability of the cellular aggregate, as well as the persistence time of the load required to induce fracture. The quantification parameters we propose here, evaluated for an in vitro model tumor without the extracellular matrix, could be applied to characterize tumor fracture under more realistic interstitial flow conditions.

中文翻译：

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时间依赖性肿瘤内压力在3D模型肿瘤中诱发的粘弹性骨折的定量表征。

在肿瘤环境中，组织间压力驱使组织间流从肿瘤核心流向淋巴管。最近的研究突出了间质压力在肿瘤发展和细胞迁移中的关键作用。据报道，癌症患者的肿瘤内压力高达60 mm Hg。在先前的研究中，我们表明，这样的压力水平会在实验性肿瘤模型中诱发骨折，该模型由包含细胞聚集体的微流体系统组成。在这里，我们调查和量化一系列流动条件下肿瘤模型骨折的特征。我们的研究结果表明粘弹性断裂行为对流动施加的载荷速率有很强的依赖性。骨料在高负荷率下表现出脆性断裂，而在低负荷率下表现出韧性断裂。加载速率还改变了细胞聚集体的渗透性，以及诱导破裂所需的负载的持续时间。我们在此提出的定量参数，用于评估不含细胞外基质的体外模型肿瘤，可用于表征更现实的组织间液流动条件下的肿瘤骨折。