Biocompatibility of direct printed clear aligners: A systematic review of in vitro studies

OBJECTIVE: Three-dimensional printing of aligners has gained in popularity as an alternative to thermoformed aligners. Only few studies evaluate the biological effects of these new materials. This systematic review aims to investigate the residual monomers leaching from direct printed clear aligners and their possible toxic effects. SEARCH METHODS: A search was conducted on several databases in accordance with PRISMA guidelines. In vitro, in vivo and clinical studies in English were included. The risk of bias of in vitro studies was assessed by QUIN Tool, for in vivo studies with the SYRCLE tool and for clinical studies with the RoB-2 tool. RESULTS: In all, 524 articles were initially identified and nine were included in the qualitative analysis. All the included studies were in vitro research with a moderate risk of bias. Seven studies were focused on cell toxicity and two on monomer release. Although mixed results are described, 3D printed aligners could present a slight cytotoxicity. Compared with thermoformed aligners, direct printed aligners had higher cytotoxicity levels. No estrogenic effects and no trace of Bisphenol A (BPA) release were detected from printed aligners when investigated but a leaching of Urethane Dimethacrylate (UDMA) have been reported in all studies. Post-curing was an important step to obtain satisfactory biocompatibility of printed aligners. CONCLUSIONS: There is no consensus on the absence of cytotoxic effects of direct printed aligners but the release of some potentially active monomers including UDMA requires further investigations on long-term effects on patients' health.