{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T15:45:08Z","timestamp":1775058308412,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T00:00:00Z","timestamp":1641168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Three-dimensional (3D) resin medical-dental devices have been increasingly used in recent years after the emergence of digital technologies. In Orthodontics, therapies with aligners have gained popularity, mainly due to the aggressive promotion policies developed by the industry. However, their systemic effects are largely unknown, with few studies evaluating the systemic toxicity of these materials. The release of bisphenol A and other residual monomers have cytotoxic, genotoxic, and estrogenic effects. This systematic review aims to analyze the release of toxic substances from 3D resins used in Orthodontics and their toxic systemic effects systematically. The PICO question asked was, \u201cDoes the use of 3D resins in orthodontic devices induce cytotoxic effects or changes in estrogen levels?\u201d. The search was carried out in several databases and according to PRISMA guidelines. In vitro, in vivo, and clinical studies were included. The in vitro studies\u2019 risk of bias was assessed using the guidelines for the reporting of pre-clinical studies on dental materials by Faggion Jr. For the in vivo studies, the SYRCLE risk of bias tool was used, and for the clinical studies, the Cochrane tool. A total of 400 articles retrieved from the databases were initially scrutinized. Fourteen articles were included for qualitative analysis. The risk of bias was considered medium to high. Cytotoxic effects or estrogen levels cannot be confirmed based on the limited preliminary evidence given by in vitro studies. Evidence of the release of bisphenol A and other monomers from 3D resin devices, either in vitro or clinical studies, remains ambiguous. The few robust results in the current literature demonstrate the absolute need for further studies, especially given the possible implications for the young patient\u2019s fertility, which constitutes one of the largest groups of patients using these orthodontic devices.<\/jats:p>","DOI":"10.3390\/bioengineering9010015","type":"journal-article","created":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T22:51:50Z","timestamp":1641250310000},"page":"15","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["The Biological Effects of 3D Resins Used in Orthodontics: A Systematic Review"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3283-5104","authenticated-orcid":false,"given":"In\u00eas","family":"Francisco","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Institute of Orthodontics, University of Coimbra, 3004-531 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6154-4173","authenticated-orcid":false,"given":"Anabela Baptista","family":"Paula","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Institute of Orthodontics, University of Coimbra, 3004-531 Coimbra, Portugal"},{"name":"Faculty of Medicine, Institute of Integrated Clinical Practice, University of Coimbra, 3004-531 Coimbra, Portugal"},{"name":"Faculty of Medicine, Area of Environment Genetics and Oncobiology (CIMAGO), Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, 3004-531 Coimbra, Portugal"},{"name":"Centre for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-531 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-531 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5682-3191","authenticated-orcid":false,"given":"Madalena","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Institute of Orthodontics, University of Coimbra, 3004-531 Coimbra, Portugal"}]},{"given":"Filipa","family":"Marques","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Institute of Orthodontics, University of Coimbra, 3004-531 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8937-361X","authenticated-orcid":false,"given":"Raquel","family":"Travassos","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Institute of Orthodontics, University of Coimbra, 3004-531 Coimbra, Portugal"}]},{"given":"Catarina","family":"Nunes","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Institute of Orthodontics, University of Coimbra, 3004-531 Coimbra, Portugal"}]},{"given":"Fl\u00e1via","family":"Pereira","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Institute of Orthodontics, University of Coimbra, 3004-531 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9269-5417","authenticated-orcid":false,"given":"Carlos Miguel","family":"Marto","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Institute of Integrated Clinical Practice, University of Coimbra, 3004-531 Coimbra, Portugal"},{"name":"Faculty of Medicine, Area of Environment Genetics and Oncobiology (CIMAGO), Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, 3004-531 Coimbra, Portugal"},{"name":"Centre for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-531 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-531 Coimbra, Portugal"},{"name":"Faculty of Medicine, Institute of Experimental Pathology, University of Coimbra, 3004-531 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5759-5557","authenticated-orcid":false,"given":"Eunice","family":"Carrilho","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Institute of Integrated Clinical Practice, University of Coimbra, 3004-531 Coimbra, Portugal"},{"name":"Faculty of Medicine, Area of Environment Genetics and Oncobiology (CIMAGO), Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, 3004-531 Coimbra, Portugal"},{"name":"Centre for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-531 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-531 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2615-2929","authenticated-orcid":false,"given":"Francisco","family":"Vale","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Institute of Orthodontics, University of Coimbra, 3004-531 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41432-020-0079-5","article-title":"Are clear aligners as effective as conventional fixed appliances?","volume":"21","author":"Kassam","year":"2020","journal-title":"Evid. 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