# Effects of Magnetic Stimulation on Dental Implant Osseointegration: A Scoping Review
## 3 Results
### In Vitro Studies  
#### 3.1.1 Static Magnetic Fields from Permanent Magnets  
Three studies treated the effects of SFM on bone cells cultured on Ti surfaces.  
[PERSON] and colleagues [32] focused on SFM generated by small neodymium-iron-bore (Nd-Fe-B) cover screws as a strategy for non-invasive and local stimulation. They performed in vitro tests, by using MG63 osteoblast-like cell line exposed or not to the magnetic cover screws (with or without Ti implants) for 24, 48 and 72 h. The reported results indicated that SFM application had a negative effect on proliferation; particularly, cells in direct contact with the magnetic cover screw (exposed to the highest magnetic flux density, reportedly 618 mT) showed the lowest proliferation rate compared to cells not exposed to SFM and cells in direct contact with Ti implants at the furthest distance from the magnetic cover screws. Despite its very low thickness, the interposition of the implant surface between cells and magnets reduced the magnetic flux and, therefore, the SFM effect on the proliferation rate. However, the major evidence of a SFM effect was related to the expression of markers of osteoblast differentiation and specifically an upregulation of genes involved in cell differentiation and matrix mineralization processes, such as transforming growth factor-\(\beta\)1 (TGF\(-\)\(\beta\)1), _COL10A1_, Bone Morphogenetic Protein-2 (_BMP-2_) for an incubation of 72 h, and a downregulation of osteoclastsing markers (_VCAM-1_).  
[PERSON] et al. [33] focused first on the interference of various MF intensities (ranging from 0 to 10 mT) with the fibronectin adsorption on the Ti surfaces without observing any significant difference compared to unexposed cells. Then, SMF effects on human osteosarcoma cells (TE-85) grown on the prepared surfaces were evaluated. While differences in the proliferation rate could not be recorded, SFM exposure caused: (i) an enhanced attachment of TE-85 cells on Ti surfaces at 1, 2, 5 and 10 mT and (ii) changes in cell morphology (strand- and sheet-like filopodia) just 2 h after cell seeding, at all applied SFM intensities. The authors hypothesized that SFM has an effect on the 3D structure of fibronectin, which could result in an increase in cell attachment index. In agreement with the reported data [32; 33], [PERSON] et al. [31] found that human bone-derived mesenchymal stem cells (hBMSCs) cultured on 3D-printed porous Ti scaffolds and exposed to increasing intensities of SFMs (50, 100, 150 mT) did not experience differences in viability and proliferation compared to unexposed controls, but showed a higher production and mineralization of ECM and a multipolar and well-spread morphology on Ti surfaces. Furthermore, the SFM exposure led to higher expression (mRNA and protein) of type-I collagen, Alkaline Phosphatase (ALP), Runt-related transcription factor-2 (RUNX2), osteopontin (OPN), and osteoclast (OCN) at 14 day, emphasizing the SFM-dependent stimulation of osteogenesis. The study also pointed mechanistically (by means of proteomic tools, western blotting and immunofluorescence) to the activation of BMP-SMAD1/5/8 signaling pathway and to SMAD4 protein increase as a key factor in the SMAD-dependent transcription activation of genes involved in osteogenic differentiation.