Related Experiment Video
Updated: Sep 21, 2026
Confocal Time Lapse Imaging as an Efficient Method for the Cytocompatibility Evaluation of Dental Composites
Published on: November 9, 2014
CYTOTOXICITY OF ORTHODONTICS ALIGNERS: AN UMBRELLA REVIEW
Catarina Nunes1, Beatriz Ornelas2, Carlos Miguel Marto3
1Institute of Orthodontics, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Laboratory for Evidence-Based Sciences and Precision Dentistry, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Centre for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal; Centre for Mechanical Engineering, Materials and Processes (CEMMPRE), Advanced Production and Intelligent Systems (ARISE), University of Coimbra, Coimbra, Portugal.
Objective:
This umbrella review aims to determine if clear aligners promote cytotoxic and estrogenic effects.
Methodology:
The review was conducted in conformity with the PRISMA statement. A systematic search was carried out in March of 2025 in 5 databases (Medline through PubMed, Web of Science (all databases), Cochrane Library, Embase, and Epistemonikos). All systematic reviews (SRs) that reported the cytotoxicity and/or estrogenicity of orthodontic aligners were included. The quality of the included studies was evaluated using AMSTAR-2 and the degree of overlap was analysed using Corrected Covered Area (CCA).
Results:
The literature search resulted in 394 articles. Screening by title and abstract, resulted in 13 articles for full reading, and 4 articles were included in the umbrella review. According to the AMSTAR-2, all reviews were of low quality. The degree of overlap among SRs is high.
Discussion:
The included SRs indicate that aligners do not have significant estrogenic/cytotoxic capacity and, even in cases of bisphenol A (BPA) leaching, this occurs at levels well below what is considered toxic. The low quality, high risk of bias, considerable overlap, and significant heterogeneity among the included studies impacts the obtained results.
Conclusion:
It is not possible to affirm or refute the presence of estrogenic or cytotoxic effects or the leaching of monomers such as BPA. In the future, it is recommended that studies adopt a more detailed and prolonged analysis of BPA leaching and it is necessary to carry out clinical studies that evaluate the safety and biocompatibility of orthodontic aligners.
