# Effects of Magnetic Stimulation on Dental Implant Osseointegration: A Scoping Review
## 4 Discussion  
To the best of our knowledge, this is the first PRISMA-driven scoping review which analyzes the effects of MFs on the dental implant osseointegration. Considering that clinical studies are still limited in number, are pioneering and are not supported by a solid and unequivocal preclinical assessment, a scoping review approach was chosen [63, 64] in order to identify and analyse the available evidence, but also knowledge gaps, and to provide indications for future research. It must be emphasised that an assessment of applied protocols indicates wide intensity and frequency ranges for the MFs used, with some studies not even reporting any MF characteristics. This makes any accurate results comparison extremely difficult. In addition, the cellular models vary considerably in the studies with both cell-lines and primary cultures used to test the in vitro effects of MFs. Particularly relevant are the investigations performed on primary hbMSC. These multipotent cells can differentiate into osteoblasts and therefore represent a particularly suitable system for evaluating the interference of chemical and physical agents on osteogenesis [65; 66; 67; 68]. Regarding the analysis of the effect of the MFs on the implant surface adhesion, both PEMF and SFM were effective in promoting the adhesion on Ti surfaces. Some differences emerge between the SFM and PEMF effects on the proliferation rate of exposed cells: in general, all the results from PEMF application show an increased proliferation rate compared to unexposed controls, regardless of the cell type used. Conversely, the application of an SFM determined no significant differences or even a reduction of the proliferation rate [32]. With regard to implant materials, some studies highlight the influence of the topographic and chemical properties of the implant surface on PEMF-induced cell response. In particular, nano-rough surface topographies proved to be the most effective in inducing early cell adhesion, early cell proliferation and osteogenic differentiation under PEMF stimulation [37], Furthermore, cell viability, proliferation, and early differentiation was significantly more pronounced on osteoblasts cultured on the cpTi surface compared to TiZr discs [38]. Finally, both PEMF and SFM appear to increase the osteoblast function in terms of upregulation of genes related to osteogenic differentiation, with a concomitant deposition of mineralized ECM [34; 35; 37; 40; 41; 42; 49]. The mechanisms through which MFs stimulate osteogenesis have been the object of several studies (reviewed in [PERSON] et al., 2019 [69] and [PERSON] et al., 2020 [70]). A direct effect seems to be exerted on the cell membrane, involving sensor structures (i.e., primary cilia) and ion, particularly calcium, flux. While PEMF treatment directly applies electric currents, SFMs can generate a biological-derived EMF with a cascade of intracellular signaling pathways. Activation of, among others, Ca- Calmodulin, PKA, MAPK, Wnt and BMP-SMADs pathways have been reported as responsible for MF-dependent induction of osteogenesis markers, although they are extremely dependent on the physical parameters of the applied MF and on the cellular context, i.e., cell type, developmental stage and tissue environment [70]. From the analysis of the studies selected for this review, it appears that PEMF might improve bone anabolism through canonical Wnt/\(\beta\)-catenin signaling [21], while activation of BMP-SMADs signaling pathway appears to be involved in SMF-induced osteogenesis [31]. According to the pro-osteogenetic effects observed in vitro, animal studies evaluating the effects of SFM on osseointegration reported higher BIC values for implants receiving SFM compared to controls [44; 45; 46]. However, more precise kinetic studies should be performed in order to characterize such effects in the different phases of osteogenesis, since no univocal results about have yet been provided [47].