Institute of Basic Medicine, Peking Union Medical College , Chinese Academy of Medical Sciences , Beijing 100005 , China.
School of Biological Sciences and Medical Engineering , Southeast University , Nanjing 210096 , China.
ACS Appl Mater Interfaces. 2018 Jul 11;10(27):22913-22923. doi: 10.1021/acsami.8b04149. Epub 2018 Jun 26.
Most of the existing scaffolds for guiding tissue regeneration do not provide direct mechanical stimulation to the cells grown on them. In this work, we used nanofibrous superparamagnetic scaffolds with applied magnetic fields to build a "dynamic" scaffold platform and investigated the modulating effects of this platform on the phenotypes of fibroblasts. The results of enzyme-linked immunosorbent and transwell assays indicated that fibroblasts cultivated in this platform secreted significantly higher type I collagen, vascular endothelial growth factor A, and transforming growth factor-β1 and did so in a time-dependent manner. At the same time, they produced fewer pro-inflammatory cytokines, including interleukin-1β and monocyte chemoattractant protein-1; this, in turn, accelerated the osteogenesis of preosteoblasts with the help of increased basic fibroblast growth factor as well as balanced extracellular matrix components. Mechanistic studies revealed that the platform modulated the phenotypic polarization of fibroblasts through the activation of components of integrin, focal adhesion kinase, and extracellular signal-regulated kinase signaling pathways and the inhibition of the activation of Toll-like receptor-4 and nuclear factor κB. Overall, the platform promoted the wound-healing phenotype of fibroblasts, which would be of great benefit to the scaffold-guided tissue regeneration.
大多数现有的组织再生引导支架并不能为其表面生长的细胞提供直接的机械刺激。在这项工作中，我们使用具有外加磁场的纳米纤维超顺磁支架构建了一个“动态”支架平台，并研究了该平台对成纤维细胞表型的调节作用。酶联免疫吸附和 Transwell 检测的结果表明，在该平台上培养的成纤维细胞分泌的 I 型胶原、血管内皮生长因子 A 和转化生长因子-β1 显著更高，且呈时间依赖性。同时，它们产生的促炎细胞因子（包括白细胞介素-1β和单核细胞趋化蛋白-1）较少；这反过来又在增加碱性成纤维细胞生长因子和平衡细胞外基质成分的帮助下，加速了前成骨细胞的成骨作用。机制研究表明，该平台通过激活整合素、粘着斑激酶和细胞外信号调节激酶信号通路的成分，以及抑制 Toll 样受体 4 和核因子 κB 的激活，调节成纤维细胞的表型极化。总的来说，该平台促进了成纤维细胞的伤口愈合表型，这将极大地有益于支架引导的组织再生。
