Endothelial cell migration is a crucial step in the process of new blood vessel formation-a necessary process to maintain cell viability inside thick tissue constructs. Here, we report a new method for maintaining cell viability and inducing cell migration using a perfused microfluidic platform based on collagen gel and a gradient hydrogel sheet. Due to the helpful role of the extracellular matrix components in cell viability, we developed a hydrogel sheet from decellularized tissue (DT) of the bovine heart and chitosan (CS). The results showed that hydrogel sheets with an optimum weight ratio of CS/DT = 2 possess a porosity of around 75%, a mechanical strength of 23 kPa, and display cell viability up to 78%. Then, we immobilized a radial gradient of vascular endothelial growth factor (VEGF) on the hydrogel sheet to promote human umbilical vein endothelial cell migration. Finally, we incorporated the whole system as an entirety on the top of the microfluidic platform and studied cell migration through the hydrogel sheet in the presence of soluble and immobilized VEGF. The results demonstrated that immobilized VEGF stimulated cell migration in the hydrogel sheet at all depths compared with soluble VEGF. The results also showed that applying a VEGF gradient in both soluble and immobilized states had a significant effect on cell migration at limited depths (<100 μm). The main finding of this study is a significant improvement in cell migration using an in vivo imitating, cost-efficient and highly reproducible platform, which may open up a new perspective for tissue engineering applications.

中文翻译：

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基于生物活性水凝胶片与灌注微流体系统相结合的诱导细胞迁移。

内皮细胞迁移是新血管形成过程中的关键步骤——这是在厚组织结构内维持细胞活力的必要过程。在这里，我们报告了一种使用基于胶原凝胶和梯度水凝胶片的灌注微流体平台来维持细胞活力和诱导细胞迁移的新方法。由于细胞外基质成分在细胞活力中的有用作用，我们从牛心脏的脱细胞组织 (DT) 和壳聚糖 (CS) 中开发了一种水凝胶片。结果表明，最佳重量比为 CS/DT = 2 的水凝胶片具有约 75% 的孔隙率、23 kPa 的机械强度和高达 78% 的细胞活力。然后，我们将血管内皮生长因子 (VEGF) 的径向梯度固定在水凝胶片上，以促进人脐静脉内皮细胞迁移。最后，我们将整个系统作为一个整体整合到微流体平台的顶部，并研究了在可溶性和固定化 VEGF 存在下细胞通过水凝胶片的迁移。结果表明，与可溶性 VEGF 相比，固定化 VEGF 在所有深度都刺激了水凝胶片中的细胞迁移。结果还表明，在可溶性和固定状态下应用 VEGF 梯度对有限深度（<100 μm）的细胞迁移有显着影响。这项研究的主要发现是使用体内模拟、经济高效和高度可重复的平台显着改善细胞迁移，