Ding Laiqian, Wang Zhongyu, Li Xinxin, Uddin Emad, Jiang Qingyun, Sun Dexian, Wei Juan, Chen Li, Liu Bo, Liu Chong, Li Jingmin
Key Laboratory for Micro/Nano Technology and System of Liaoning Province, Dalian University of Technology, Dalian 116024, China.
School of Mechanical & Manufacturing Engineering, National University of Sciences and Technology, Islamabad 44000, Pakistan.
Analyst. 2025 Jul 21;150(15):3298-3310. doi: 10.1039/d5an00582e.
Tumor cell migration plays a significant role in the processes of local invasion and distant metastasis, closely related to the high mortality rate of malignancies. The mechanical properties of the extracellular matrix can regulate tumor cell behaviors. However, classical methods for studying cell migration mostly use stiffer (≥MPa level) materials to mimic the physical microenvironments, neglecting the viscoelasticity of soft physiological tissues containing a dynamic interstitial fluid microenvironment. In this paper, a versatile microfluidic device integrated with a hydrogel for wound healing assays is proposed to investigate the effects of matrix viscoelasticity on tumor cell migration. A long, narrow cell-free area with a width of 500 μm is created to simulate a wound at the bottom of the chamber by adjusting the pressure imposed on the upper layer of the device. The flow fields in the chambers are evaluated by numerical simulation and particle tracking assays. Viscoelastic and elastic hydrogels with similar compressive moduli (∼2 kPa) are used to mimic the mechanical microenvironments. HeLa cells are cultured in hydrogel extracts to assess their cytotoxicity. For wound healing assays, hydrogels are perfused into the chambers of the device and cover the cell monolayer and cell-free area. The higher closure of the wound exposed to the viscoelastic hydrogel indicates that hydrogel viscoelasticity can promote tumor cell migration. The wound healing assays also show a dose-dependent response to doxorubicin hydrochloride treatment. All results demonstrate that the proposed microfluidic strategy provides a prospective platform for cell research and anti-cancer drug screening.
肿瘤细胞迁移在局部侵袭和远处转移过程中起着重要作用，这与恶性肿瘤的高死亡率密切相关。细胞外基质的力学性质可以调节肿瘤细胞的行为。然而，经典的细胞迁移研究方法大多使用较硬（≥兆帕水平）的材料来模拟物理微环境，而忽略了含有动态间质液微环境的柔软生理组织的粘弹性。本文提出了一种集成水凝胶的多功能微流控装置用于伤口愈合检测，以研究基质粘弹性对肿瘤细胞迁移的影响。通过调节施加在装置上层的压力，在腔室底部创建一个宽度为500μm的狭长无细胞区域来模拟伤口。通过数值模拟和粒子追踪检测来评估腔室内的流场。使用具有相似压缩模量（约2kPa）的粘弹性和弹性水凝胶来模拟力学微环境。将HeLa细胞培养在水凝胶提取物中以评估其细胞毒性。对于伤口愈合检测，将水凝胶灌注到装置的腔室中并覆盖细胞单层和无细胞区域。暴露于粘弹性水凝胶的伤口具有更高的闭合率，这表明水凝胶的粘弹性可以促进肿瘤细胞迁移。伤口愈合检测还显示了对盐酸阿霉素治疗的剂量依赖性反应。所有结果表明，所提出的微流控策略为细胞研究和抗癌药物筛选提供了一个有前景的平台。
