MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
Langmuir. 2013 May 28;29(21):6386-95. doi: 10.1021/la4004609. Epub 2013 May 14.
Directional migration of cells mediated by gradient cues in vitro can mimic the corresponding biological events in vivo and thereby provides a way to disclose the cascade responses in tissue regeneration processes and to develop novel criteria for design of tissue-inductive biomaterials. In this work, a molecular weight gradient of poly(2-hydroxyethyl methacrylate) (PHEMA) brushes with a thickness ranging from 3 to 30 nm and slopes of 0.8-3.2 nm/mm were fabricated by using surface-initiated atom transfer radical polymerization (ATRP) and a dynamically controlled reaction process. The PHEMA gradients were characterized by X-ray photoelectron spectrometry (XPS) and ellipsometry. The adhesion number, spreading area, adhesion force, and expression of focal adhesion and actin fibers of vascular smooth muscle cells (VSMCs) decreased along with the increase of the PHEMA brushes length. The VSMCs exhibited preferential orientation and enhanced directional migration toward the direction of reduced PHEMA thickness, whose extent was dependent on the gradient slope and polymer thickness. Most of the cells were oriented, and 87% of the cells moved directionally at the optimal conditions.
体外梯度线索诱导的细胞定向迁移可以模拟体内相应的生物学事件,从而为揭示组织再生过程中的级联反应提供了一种方法,并为设计组织诱导性生物材料制定了新的标准。在这项工作中,采用表面引发原子转移自由基聚合(ATRP)和动态控制反应过程,制备了厚度为 3 至 30nm 且斜率为 0.8-3.2nm/mm 的聚(2-羟乙基甲基丙烯酸酯)(PHEMA)刷的分子量梯度。通过 X 射线光电子能谱(XPS)和椭圆光度法对 PHEMA 梯度进行了表征。随着 PHEMA 刷长度的增加,血管平滑肌细胞(VSMCs)的黏附数量、铺展面积、黏附力以及焦点黏附和肌动蛋白纤维的表达均降低。VSMCs 表现出向 PHEMA 厚度减小方向的择优取向和增强的定向迁移,其程度取决于梯度斜率和聚合物厚度。大多数细胞被定向,并且在最佳条件下 87%的细胞呈定向迁移。