Cell migration is an essential process involved in crucial stages of tissue formation, regeneration or immune function as well as in pathological processes including tumor development or metastasis. During the last few years, the effect of gradients of soluble molecules on cell migration has been widely studied, and complex systems have been used to analyze cell behavior under simultaneous mechano-chemical stimuli. Most of these chemotactic assays have, however, focused on specific substrates in 2D. The aim of the present work is to develop a novel microfluidic-based chip that allows the long-term chemoattractant effect of growth factors (GFs) on 3D cell migration to be studied, while also providing the possibility to analyze the influence of the interface generated between different adjacent hydrogels. Namely, 1.5, 2, 2.5 and 4 mg ml-1 concentrations of collagen type I were alternatively combined with 5, 10 or 50 ng ml-1 concentrations of PDGF and VEGF (as a negative control). To achieve this goal, we have designed a new microfluidic device including three adjacent chambers to introduce hydrogels that allow the generation of a collagen concentration step gradient. This versatile and simple platform was tested by using dermal human fibroblasts embedded in 3D collagen matrices. Images taken over a week were processed to quantify the number of cells in each zone. We found, in terms of cell distribution, that the presence of PDGF, especially in small concentrations, was a strong chemoattractant for dermal human fibroblasts across the gels regardless of their collagen concentration and step gradient direction, whereas the effects of VEGF or collagen step gradient concentrations alone were negligible.

中文翻译：

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使用胶原蛋白水凝胶浓度的阶跃梯度来量化基于微流体的芯片中的3D趋化性。

细胞迁移是涉及组织形成，再生或免疫功能的关键阶段以及包括肿瘤发展或转移在内的病理过程的重要过程。在最近几年中，可溶分子梯度对细胞迁移的影响已得到广泛研究，并且复杂的系统已被用于分析在同时机械化学刺激下的细胞行为。然而，大多数这些趋化测定法都集中在二维的特定底物上。本工作的目的是开发一种新型的基于微流体的芯片，该芯片可以研究生长因子（GFs）对3D细胞迁移的长期化学吸引作用，同时还提供了分析所产生界面的影响的可能性在不同的相邻水凝胶之间。即1.5、2、2。将5和4 mg ml-1浓度的I型胶原与5、10或50 ng ml-1浓度的PDGF和VEGF组合（作为阴性对照）。为了实现这一目标，我们设计了一种新的微流控设备，该设备包括三个相邻的腔室，以引入水凝胶，从而产生胶原蛋白浓度阶跃梯度。通过使用嵌入3D胶原蛋白基质中的真皮人成纤维细胞，测试了这个多功能，简单的平台。处理一周内拍摄的图像以量化每个区域中的细胞数量。我们发现，就细胞分布而言，PDGF的存在，特别是小浓度的PDGF，对于真皮中的人类成纤维细胞而言，无论其胶原蛋白浓度和阶跃梯度方向如何，都是一种强大的化学吸引剂，