Directional cell migration plays an important role in embryonic development, tissue regeneration, wound healing, and proper immune responses. In order to control cell migration, various gradient biomaterials have been fabricated. Although most of these systems have been designed to study cell migration in the horizontal (XY) plane, the migration of cells in the vertical plane (bottom to top: XZ) is crucial for wound healing, development of the cerebellum, and metastatic processes. In this study, we designed new step-gradient nanocomposite (NC) scaffolds by 3D printing different layers of NC hydrogels containing increasing concentrations of bifunctional nanomaterials (NMs). The synthesized bifunctional NMs are stimuli (pH) responsive and, when integrated into the 3D network of the step-gradient NC scaffolds, provide sustained release of bioactive molecules, which is beneficial for local drug delivery applications. We demonstrate that bifunctional NMs used in vertically increasing concentrations can influence the migration of cells in the XZ plane of the step-gradient NC scaffolds. Further, the bifunctional NMs improve the viability of healthy cells and promote their migration in the XZ plane of the step-gradient NC scaffolds, they simultaneously inhibit the concurrent migration and growth of cancer cells due to the pH-responsive release of bioactive molecules.

中文翻译：

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通过双功能纳米材料在3D渐变纳米复合水凝胶中定向垂直细胞迁移

定向细胞迁移在胚胎发育，组织再生，伤口愈合和适当的免疫反应中起重要作用。为了控制细胞迁移，已经制造了各种梯度生物材料。尽管这些系统中的大多数已设计为研究水平面（XY）平面中的细胞迁移，但细胞在垂直平面中的迁移（底部到顶部：XZ）对于伤口愈合，小脑发育和转移过程至关重要。在这项研究中，我们通过3D打印包含增加浓度的双功能纳米材料（NMs）的NC水凝胶的不同层，设计了新的逐步梯度纳米复合材料（NC）支架。合成的双功能NM具有刺激性（pH）响应，当整合到逐步梯度NC支架的3D网络中时，可提供生物活性分子的持续释放，这对于局部药物递送应用非常有利。我们证明在垂直增加的浓度中使用的双功能NMs可以影响逐步梯度NC支架的XZ平面中的细胞迁移。此外，双功能NM可改善健康细胞的活力并促进其在XZ中的迁移 在梯度梯度NC支架的平面上，由于生物活性分子的pH响应释放，它们同时抑制了癌细胞的同时迁移和生长。