# Magnetism in Dentistry: Review and Future Perspectives
## 3 SPIONs in the Biomedicine
It has been already proved that it would be possible to obtain magnetic field gradients capable to attract bioaggregates into the completely biodegradable scaffolds with a fully interconnected pore network just embedding a small amount of superparamagnetic nanoparticles in polymer matrix [103; 107; 108]. In vivo pilot experiments, carried out in rabbit animal model, suggested that 3D nanocomposite magnetic scaffold could represent a potential innovative option to autologous bone implantation [103; 107; 108]. Furthermore, magnetic force may induce adaptive changes in microenvironments, including the cell matrix, cell membrane, cytoskeleton, nucleoprotein, and genome. Consequently, signals are transduced to the cell nucleus, regulating and stimulating different biological responses. The design and development of fully bio-degradable and magnetic nanocomposite substrates and the correlation between the application of a time-dependent magnetic field and hMSCs biological performance has been studied [109]. In particular, Alamar Blue assay, ALP activity normalized for the DNA content (ALP/DNA), CLSM analysis and cell shape factor, p-ERK1/2 expression suggested interesting and, sometimes in many cases, unreported information, on the synergistic combination of PCL/Fe\({}_{3}\)O\({}_{4}\) magnetic nanocomposites with a discontinuous application of the external magnetic field on cell behaviour over time: the use of the time-dependent magnetic field enhanced the activation of the MAPK pathway, as evidenced by an increase of ERK phosphorylation for both PCL and PCL/Fe\({}_{3}\)O\({}_{4}\) scaffolds [109]. On the same way, multifunctional hybrid scaffolds have been proposed to reproduce the different features of periodontal ligament, alveolar bone, and cementum. Specifically, the integration of biomineralization process, electrospinning techniques and tape casting have been brought together, also employing superparamagnetic apatite phase for promoting osteogenesis via remote magnetic field signals. The periodontal scaffold has been obtained by engineering three different layers, reproducing the crucial compositional and microstructural features of the target tissues, into a monolithic multifunctional graded device. Results confirm that the proposed biocompatibility structure exhibits a good mimicry of the periodontal tissue complex, making innovative regenerative applications in dentistry [110]. A preliminary concept of multifunctional CaP-based scaffolds obtained via additive manufacturing from an innovative ink composition, with potential for bone tissue regeneration, drug delivery and cancer treatment by local magnetic hyperthermia platforms has been demonstrated. A highly loaded ink composed by iron-doped hydroxyapatite and \(\beta\)-tricalcium phosphate powders mixed in a chitosan-based solution, in the presence of levofloxacin (LEV) as model drug and magnetic nanoparticles (MNP) have been used, highlighting a synergistic effect between the iron-doped CaP-based powders and the MNP due to ferro/ferrimagnetic interactions. Furthermore, the iron presence enhances human mesenchymal stem cell metabolic activity and proliferation [111]. Additive manufactured magnetic scaffolds have been also proposed as a novel strategy for three-dimensional magnetic patterning of two cell types in vitro, also as a conceptual precursor for the vascularised tissue. The realisation of separate arrangements of vascular and osteoprogenitor cells, labelled with biocompatible magnetic nanoparticles, was established adopting nonhomogeneous magnetic gradients and loading magnetic configuration. It has been shown that scaffold magnetisation was able to amplify the cell guiding effects by an additional trapping of cells due to short range magnetic forces. Thus, the proposed solution should be employed as a compact assembled strategy for adequate arrangement of cellular constructs [112].