Kazantseva Jekaterina, Ivanov Roman, Gasik Michael, Neuman Toomas, Hussainova Irina
Cellin Technologies LLC, Mäealuse 4, Tallinn 12618, Estonia.
Department of Mechanical and Industrial Engineering, Tallinn University of Technology, Ehitajate 5, Tallinn 19086, Estonia.
ACS Biomater Sci Eng. 2018 May 14;4(5):1622-1629. doi: 10.1021/acsbiomaterials.8b00228. Epub 2018 Apr 20.
Three-dimensional (3D) customized scaffolds are anticipated to provide new frontiers in cell manipulation and advanced therapy methods. Here, we demonstrate the application of hybrid 3D porous scaffolds, representing networks of highly aligned self-assembled ceramic nanofibers, for culturing four types of cancer cells. Ultrahigh aspect ratio (∼10) of graphene augmented fibers of tailored nanotopology is shown as an alternative tool to substantially affect cancerous gene expression, eventually due to differences in local biomechanical features of the cell-matrix interactions. Here, we report a clear selective up- and down-regulation of groups of markers for breast cancer (MDA-MB231), colorectal cancer (CaCO2), melanoma (WM239A), and neuroblastoma (Kelly) depending on only fiber orientation and morphology without application of any other stimulus. Changes in gene expression are also revealed for Mitomycin C treatment of MDA-MB231, making the scaffold a suitable platform for testing of anticancer agents. This allows an opportunity for selective "clean" guidance to a deep understanding of mechanisms of cancer cells progressive growth and tumor formation without possible side effects by manipulation with the specific markers.
三维(3D)定制支架有望为细胞操控和先进治疗方法开辟新领域。在此,我们展示了混合3D多孔支架的应用,该支架代表高度排列的自组装陶瓷纳米纤维网络,用于培养四种癌细胞。具有定制纳米拓扑结构的石墨烯增强纤维的超高长径比(约10)被证明是一种可显著影响癌基因表达的替代工具,最终是由于细胞 - 基质相互作用的局部生物力学特征存在差异。在此,我们报告,仅根据纤维方向和形态,在不施加任何其他刺激的情况下,乳腺癌(MDA - MB231)、结直肠癌(CaCO2)、黑色素瘤(WM239A)和成神经细胞瘤(Kelly)的标志物组出现明显的选择性上调和下调。丝裂霉素C处理MDA - MB231后也揭示了基因表达的变化,这使得该支架成为测试抗癌药物的合适平台。这为选择性“精准”引导提供了契机,有助于深入了解癌细胞渐进性生长和肿瘤形成的机制,且通过操控特定标志物不会产生可能的副作用。