Insights into the Molecular Mechanisms Regulating Cell Behavior in Response to Magnetic Materials and Magnetic Stimulation in Stem Cell (Neurogenic) Differentiation.

Magnetic materials and magnetic stimulation have gained increasing attention in tissue engineering (TE), particularly for bone and nervous tissue reconstruction. Magnetism is utilized to modulate the cell response to environmental factors and lineage specifications, which involve complex mechanisms of action. Magnetic fields and nanoparticles (MNPs) may trigger focal adhesion changes, which are further translated into the reorganization of the cytoskeleton architecture and have an impact on nuclear morphology and positioning through the activation of mechanotransduction pathways. Mechanical stress induced by magnetic stimuli translates into an elongation of cytoskeleton fibers, the activation of linker in the nucleoskeleton and cytoskeleton (LINC) complex, and nuclear envelope deformation, and finally leads to the mechanical regulation of chromatin conformational changes. As such, the internalization of MNPs with further magnetic stimulation promotes the evolution of stem cells and neurogenic differentiation, triggering significant changes in global gene expression that are mediated by histone deacetylases (e.g., HDAC 5/11), and the upregulation of noncoding RNAs (e.g., miR-106b~25). Additionally, exposure to a magnetic environment had a positive influence on neurodifferentiation through the modulation of calcium channels' activity and cyclic AMP response element-binding protein (CREB) phosphorylation. This review presents an updated and integrated perspective on the molecular mechanisms that govern the cellular response to magnetic cues, with a special focus on neurogenic differentiation and the possible utility of nervous TE, as well as the limitations of using magnetism for these applications.

Gelatin Meshes Enriched with Graphene Oxide and Magnetic Nanoparticles Support and Enhance the Proliferation and Neuronal Differentiation of Human Adipose-Derived Stem Cells.

The field of tissue engineering is constantly evolving due to the fabrication of novel platforms that promise to stimulate tissue regeneration in the scenario of accidents. Here, we describe the fabrication of fibrous nanostructured substrates based on fish gelatin (FG) and enriched with graphene oxide (GO) and magnetic nanoparticles (MNPs) and demonstrate its biological properties in terms of cell viability and proliferation, cell adhesion, and differentiation. For this purpose, electrospun fibers were fabricated using aqueous precursors containing either only GO and only MNP nanospecies, or both of them within a fish gelatin solution. The obtained materials were investigated in terms of morphology, aqueous media affinity, tensile elasticity, and structural characteristics. The biological evaluation was assessed against adipose-derived stem cells by MTT, LDH, Live/Dead assay, cytoskeleton investigation, and neuronal trans-differentiation. The results indicate an overall good interaction and show that these materials offer a biofriendly environment. A higher concentration of both nanospecies types induced some toxic effects, thus 0.5% GO, MNPs, and GO/MNPs turned out to be the most suitable option for biological testing. Moreover, a successful neuronal differentiation has been shown on these materials, where cells presented a typical neuronal phenotype. This study demonstrates the potential of this scaffold to be further used in tissue engineering applications.