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(1) Background: The use of removable orthodontic appliances, which is common in early ages, requires careful hygiene, as several different microorganisms are found on their surface during the orthodontic treatment. (2) Methods: Comprehensive electronic searches were conducted up to May 2021. Randomized controlled trials (RCTs) or controlled clinical trials (CCTs), prospective or retrospective, evaluating the efficacy of cleaning and disinfection methods for acrylic removable orthodontic appliances, redacted in the English language, were included. Three independent blinding review authors were involved in study selection, data extraction, and bias assessment. (3) Results: A total of 2491 records were screened and eight studies (six RCTs and two CCTs) fulfilled the inclusion criteria. Among the overall cleaning and disinfection methods described in the included studies, four categories could be defined: liquid antimicrobial agents, commercial tablet cleansers, natural plant extracts and incorporation of quaternary ammonium methacryloxy silicate, all of which demonstrated superior efficacy compared to the placebo/negative control. However, the different methods were not compared with each other. (4) Conclusions: Biofilm control on acrylic orthodontic removable appliances can be performed using the different cleaning and disinfection methods considered in the included studies. Further studies are needed to define the most effective technique. Registration: PROSPERO CRD 42021269297.

What Are the Cleaning and Disinfection Methods for Acrylic Orthodontic Removable Appliance? A Systematic Review