<b>Genotoxic and Cytotoxic Effects Induced by Orthodontic Appliances on the Buccal Mucosal Cells: A Systematic Review</b>

Background: Orthodontic appliances are widely used for the correction of malocclusion and improvement of oral function and aesthetics. These appliances are fabricated from various metallic and polymeric materials that remain in prolonged contact with oral tissues, raising concerns regarding potential genotoxic and cytotoxic effects on oral epithelial cells due to ion release, corrosion, and material degradation in the oral environment. Objective: To systematically evaluate the available in vivo human evidence on the genotoxic and cytotoxic effects induced by orthodontic appliances on buccal mucosal cells. Methods: A systematic literature search was conducted using PubMed, Scopus, Google Scholar, and ProQuest databases following PRISMA guidelines. Clinical in vivo studies assessing genotoxicity and/or cytotoxicity of fixed or removable orthodontic appliances using micronucleus testing, Comet assay, or cell viability-related methods were included. Data extraction and quality assessment were performed independently by two reviewers using Joanna Briggs Institute criteria, and findings were synthesized narratively due to methodological heterogeneity. Results: Five clinical studies involving 185 participants were included. Two studies reported increased DNA damage and reduced cell viability following prolonged exposure to fixed orthodontic appliances. Other studies demonstrated no significant increase in micronuclei frequency in buccal mucosal cells, while one study reported localized genotoxic effects in palatal cells associated with removable acrylic appliances. Overall findings were inconsistent and influenced by appliance type, material composition, exposure duration, and tissue site assessed. Conclusion: Orthodontic appliances may induce mild and inconsistent genotoxic or cytotoxic effects on oral epithelial cells, which appear to be transient in most cases. Further well-designed longitudinal studies with standardized biomonitoring protocols are required to clarify clinical relevance and support the development of highly biocompatible orthodontic materials