Combination Design of Time-Dependent Magnetic Field and Magnetic Nanocomposites to Guide Cell Behavior

The concept of magnetic guidance is still challenging and has opened a wide range of perspectives in the field of tissue engineering. In this context, magnetic nanocomposites consisting of a poly(epsilon-caprolactone) (PCL) matrix and iron oxide (Fe3O4) nanoparticles were designed and manufactured for bone tissue engineering. The mechanical properties of PCL/Fe3O4 (80/20 w/w) nanocomposites were first assessed through small punch tests. The inclusion of Fe3O4 nanoparticles improved the punching properties as the values of peak load were higher than those obtained for the neat PCL without significantly affecting the work to failure. The effect of a time-dependent magnetic field on the adhesion, proliferation, and differentiation of human mesenchymal stem cells (hMSCs) was analyzed. The Alamar Blue assay, confocal laser scanning microscopy, and image analysis (i.e., shape factor) provided information on cell adhesion and viability over time, whereas the normalized alkaline phosphatase activity (ALP/DNA) demonstrated that the combination of a time-dependent field with magnetic nanocomposites (PCL/Fe3O4 Mag) influenced cell differentiation. Furthermore, in terms of extracellular signal-regulated kinase (ERK)1/2 phosphorylation, an insight into the role of the magnetic stimulation was reported, also demonstrating a strong effect due the combination of the magnetic field with PCL/Fe3O4 nanocomposites (PCL/Fe3O4 Mag).