Integration of a Superparamagnetic Scaffold and Magnetic Field To Enhance the Wound-Healing Phenotype of Fibroblasts.

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.