Motealleh Andisheh, Kehr Nermin S
Physikalisches Institute and Center for Soft Nanoscience, Westfälische Wilhelms-Universität Münster, Busso-Peus-Strasse 10, 48149 Münster, Germany.
Biomater Sci. 2020 Oct 21;8(20):5628-5637. doi: 10.1039/d0bm01133a. Epub 2020 Sep 30.
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.
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着重要作用。为了控制细胞迁移，人们制备了各种梯度生物材料。尽管这些系统大多设计用于研究细胞在水平（XY）平面内的迁移，但细胞在垂直平面（从底部到顶部：XZ）内的迁移对于伤口愈合、小脑发育和转移过程至关重要。在本研究中，我们通过3D打印不同层含有浓度递增的双功能纳米材料（NMs）的NC水凝胶，设计了新型阶梯梯度纳米复合材料（NC）支架。合成的双功能NMs对刺激（pH）有响应，当整合到阶梯梯度NC支架的3D网络中时，可实现生物活性分子的持续释放，这有利于局部药物递送应用。我们证明，浓度垂直递增的双功能NMs可影响阶梯梯度NC支架XZ平面内细胞的迁移。此外，双功能NMs提高了健康细胞的活力，并促进其在阶梯梯度NC支架的XZ平面内迁移，同时由于生物活性分子的pH响应释放，它们抑制了癌细胞的同时迁移和生长。
