Ferreira, MarianaCosta, HélderVeiga, NélioCorreia, Maria J.Gomes, Ana T. P. C.Lopes, Pedro C.2025-08-132025-08-132025-05-10Ferreira, M., Costa, H., Veiga, N., & Correia, M. J. et al. (2025). Do clear aligners release toxic chemicals? - a systematic review. Journal of Functional Biomaterials, 16(5), Article 173. https://doi.org/10.3390/jfb160501732079-4983040f9f1e-e510-46f8-9d61-c545739d3e7chttp://hdl.handle.net/10400.14/54559Clear aligners are a modern orthodontic solution designed to address dental malocclusions discreetly and effectively. In terms of clinical side effects, the most reported issues among aligner users are mild irritation of the oral mucosa, localized inflammation, and hypersensitivity. The use of advanced polymer materials in clear aligners, such as polyurethane and PET-G, has gained widespread acceptance due to their mechanical properties, biocompatibility, and aesthetic appeal. However, concerns persist regarding their potential to release chemical compounds. Our goal is to understand the impact of clear aligner toxicity on the oral cavity of orthodontic patients. An extensive systematic search was conducted in the electronic databases PubMed, Scopus, and Cochrane to identify articles with relevant data. This systematic review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines (PRISMA) to answer a question formulated according to the Population, Intervention, Comparison, and Outcomes. Four hundred and thirteen articles potentially relevant were identified and after applying PRISMA guidelines and inclusion/exclusion criteria, seven articles were included in this review. Our results suggest that clear aligners are generally safe, but concerns remain regarding the chemical leaching of thermoplastic materials, bacterial accumulation due to reduced saliva flow, and mild inflammatory responses. Our review emphasizes that although most materials are biocompatible, some exhibit moderate cytotoxicity, with the potential to impact these patients’ oral health, underscoring the need for continued research and improvements in material composition.engAdvanced polymer materialsClear alignersCytotoxicityOrthodonticsreview article10.3390/jfb16050173105006541814001496763800001