# Magnetism in Dentistry: Review and Future Perspectives
## 3 SPIONs in the Biomedicine

Table 1: Additive manufacturing methods for oral tissue engineering. Adapted from [2]. molecules, can act as markers of specific cells in vivo; they can be used, for example, to identify tumour areas especially in the liver and lymph nodes. Another application is to functionalize the SPIONs with specific ligands for some biomolecules to act as a DNA marker to identify \"wrong\" sequences. Tissue repair involves transplanting stem cells into injured tissues, which growing, proliferating, and differentiating repair tissue damage. In this field the SPIONs have been proposed as tools to support stem cells and allow their delivery to desired sites. If the stem cells are labelled with SPIONs, it makes it easier to trace them inside the body using, for example, MRI. In doing so, in fact, it will be possible to follow the path of stem cells in vivo without using invasive techniques [88,89]. SPIONs are biocompatible magnetic nanoparticles and approved by the Food and Drug Administration (FDA) as contrast agents. The magnetic susceptibility of the nanoparticles makes the whole system a good contrast agent for MRI; moreover, they can undergo superficial modifications allowing different types of stem cells anchoring. Superparamagnetic nanocrystals of iron oxides act as contrast agents in MRI (magnetic resonance imaging), a technique used in the medical field that measures the relaxation of proton nuclear spin in tissues, managing to transform the signals into an image. Micrometric magnetic particles or chelated complexes of magnetic ions injected into tissues act as proton relaxation agents. Magnetic nanocrystals offer the advantage of being able to flow in the blood for a longer time than larger crystals, thus providing capillary walls crossing and reaching the lymph nodes. The use of hyperthermia for malignant tumours treatment have been widely investigated. The magnetic field cannot be absorbed by living tissues and is applied to deep areas of the body. When magnetic nanoparticles undergo the action of an alternating magnetic field, the magnetic loss of hysteresis generates heat. The amount of generated heat varies according to the nature of the magnetic material and the parameters of the field. The magnetic particles incorporated inside the tumour cells subjected to an oscillating magnetic field, warm up, reaching a different temperature that depends on the strength of the magnetic field, the magnetic properties of the material, the frequency of oscillation and the cooling capacity of the blood flow in the site where the tumour is present. Therefore, as cancer cells are sensitive to high temperatures will be destroyed when the temperature reaches values close to or above 43 \({}^{\circ}\)C, while normal cells, more resistant to high temperatures, will survive [90]. In magnetofection, superparamagnetic nanoparticles linked with DNA vectors are transfected inside the cells through the application of the external magnetic field. For this reason, superparamagnetic nanoparticles must be coated with polycations, such as polyethylene (PEI) [91]. SPIONs are able to release the gene of interest into the nucleus, once passed the endosomal barrier. Nanoparticles will be forced to follow the magnetic field by using permanent or alternating magnets, thus avoiding free diffusion. Recently, systems based on SPIONs and corticosteroids, have been shown to be useful in solving the problem related to arthritis therapy. In particular, corticosteroids directly injected directly into the affected joints can cause crystals formation over time and consequent joint infections. By using the external magnetic field, these systems can be retained in the joint capsules avoiding repeated injections and elimination due to macrophage and drainage systems [92]. Finally, an important application of SPIONs provides for the specific distribution of the drug, drug delivery systems (DDS), at the site of action. The functionalization of the surface of the SPIONs makes them excellent drug carriers that are thus directed into the organ target and released there.