Magnetic nanocomposite scaffolds combined with static magnetic field in the stimulation of osteoblastic differentiation and bone formation

Magnetism has recently been implicated to play significant roles in the regulation of cell responses. Allowing cells to experience a magnetic field applied externally or scaffolding them in a material with intrinsic magnetic properties has been a possible way of utilizing magnetism. Here we aim to investigate the combined effects of the external static magnetic field (SMF) with magnetic nanocomposite scaffold made of polycaprolactone/magnetic nanoparticles on the osteoblastic functions and bone formation. The SMF synergized with the magnetic scaffolds in the osteoblastic differentiation of primary mouse calvarium osteoblasts, including the expression of bone-associated genes (Runx2 and Osterix) and alkaline phosphatase activity. The synergism was demonstrated in the activation of integrin signaling pathways, such as focal adhesion kinase, paxillin, RhoA, mitogen-activated protein kinase, and nuclear factor-kappaB, as well as in the up-regulation of bone morphogenetic protein-2 and phosphorylation of Smad1/5/8. Furthermore, the SMF/magnetic scaffold-stimulated osteoblasts promoted the angiogenic responses of endothelial cells, including the expression of vascular endothelial growth factor and angiogenin-1 genes and the formation of capillary tubes. When the magnetic scaffolds were implanted in mouse calvarium defects, the application of SMF significantly enhanced the new bone formation at 6 weeks, as revealed by the histological and micro-computed tomographic analyses. Current findings suggest that the combinatory application of external (SMF) and internal (scaffold) magnetism can be a promising tool to regenerative engineering of bone.