# Cytotoxicity of Orthodontic Archives Used in Clinical Practice: In Vitro Study
## 4 Discussion  
### Review of the Literature  
As mentioned in Section 1, [PERSON] and [PERSON] [1] emphasize that an ideal orthodontic wire should possess not only optimal physical characteristics such as elasticity, stiffness, malleability, and low friction but also essential chemical traits, particularly biocompatibility and stability, to function effectively in fluctuating conditions of the oral cavity. The biocompatibility of components used in fixed thin-arch orthodontic devices is determined both by their composition and resistance to corrosion, that is, by their ability to release metal ions. It must be emphasized that the specific, \"aggressive\" conditions prevailing in the oral cavity (such as variable pH, temperature, microbial colonization) create favorable conditions for various types of corrosion, which occurs in all metal alloys used in orthodontics, as noted by [PERSON] [12]. The principles for the biological evaluation of medical devices are specified in ISO 10993 [13]; however, ISO 15841 [14] and the ADA specification No. 32, relating to orthodontic wires, do not contain clear guidelines for the evaluation of ion release, which are pointed out by [PERSON] and [PERSON] [7], leading to a diversity of methods for testing arches both in vitro and in vivo. Common methods to assess the biocompatibility of metal alloys in orthodontics include examining the impact of metals on cell cultures and analyzing ion release in solutions such as artificial saliva or NaCl. Due to potential allergenic, cytotoxic, and mutagenic properties, the effects of nickel and chromium ions are most frequently assessed in biocompatibility studies. Nickel, being a component of alloys, is considered potentially toxic and is capable of causing gum inflammation even in non-allergic individuals with good hygiene, as stated by [PERSON] [10]. However, opinions on NiTi arches in the literature are divided, being described as both toxic [15] and non-toxic [16; 17; 18]. The results of the in vitro study on the cytotoxic action of released metal ions are varied. [PERSON] and associates found that nickel-chromium alloys were nontoxic in the agar diffusion test, and microscopic observation of cells exposed to nickel-containing alloys showed no differences compared to those of the control group. In contrast, [PERSON] and [PERSON] [19] observed toxic cellular reactions in the form of reduced proliferation of gingival fibroblasts, similarly as reported by [PERSON] et al. [20] and [PERSON] et al. [21]. Meanwhile, studies by [PERSON] et al. [22] and [PERSON] et al. [23] present diverse results regarding the impact of orthodontic arches on cells. Based on research by [PERSON] [24], the results of cell viability and proliferation tests showed the following order of biocompatibility of alloys: steel > nickel-titanium alloys > titanium. The most favorable ratio of living cells to dead cells was found in nickel-titanium alloys > titanium > steel > nickel. Several modern studies have explored the cytotoxic effects of orthodontic archives. [PERSON] et al. [25] found that while NiTi archives generally show minimal direct cytotoxicity, their physical and chemical properties, such as surface microstructures and corrosion resistance, can influence cellular responses. [PERSON] et al. [26] observed minimal cytotoxic effects in most orthodontic wires after use, except Polytetrafluoroethylene PTFE-coated copper-nickel-titanium wires, which demonstrated significant reductions in cell viability and changes in chemical composition and surface wear. [PERSON] et al. [27] highlighted that recasting dental alloys affects cytotoxicity levels and metal ion release, impacting the biocompatibility of Co-Cr, Ni-Cr, and Au-Pt materials. [PERSON] [28] noted that the cytotoxicity of nickel-titanium orthodontic wires vary over time, increasing in cytotoxicity after 30 days, contrasting with the stable biocompatibility of others. These findings underscore the varying impacts of material properties and usage duration on the safety and effectiveness of orthodontic wires.