From Polyethylene Terephthalate Glycol (PETG) to 3D-Printed Resins: A Systematic Review and Meta-Analysis of Clear Aligner Material Performance and Safety.

Clear aligner therapy depends on polymeric materials that differ in stiffness, elasticity, force retention, surface stability, optical behavior, and biological safety. Polyethylene terephthalate glycol (PETG), thermoplastic polyurethane (TPU), polyurethane (PU), copolyesters, multilayer polymers, polypropylene/polyethylene (PP/PE)-based materials, and three-dimensional (3D)-printed resins are increasingly used, but their comparative performance remains heterogeneous. This systematic review and meta-analysis evaluated the mechanical performance, aging behavior, cytotoxicity, chemical release, microplastic release, and surface stability of orthodontic clear aligner materials. PubMed/MEDLINE, Scopus, Web of Science Core Collection, Cochrane Library, Google Scholar, Embase, and ScienceDirect were searched for English-language full-text studies published from January 2000 through June 23, 2026. Eligible studies evaluated material-specific mechanical, optical, biological, chemical, surface, or clinically relevant outcomes. Findings were synthesized narratively, and exploratory random-effects quantitative syntheses were conducted when numerical outcomes were sufficiently compatible. Methodological quality was evaluated using the Quality Assessment Tool for In Vitro Studies (QUIN) for the 22 laboratory investigations and the Joanna Briggs Institute (JBI) critical appraisal checklist for quasi-experimental studies for the prospective clinical/laboratory investigation. The review was not prospectively registered. Twenty-three studies were included, of which 22 were predominantly in vitro laboratory investigations. PETG, TPU, polyurethane, copolyesters, multilayer polymers, PP/PE-based materials, and direct 3D-printed resins showed substantial variation in modulus, flexural performance, stress relaxation, force decay, aging response, and surface roughness. QUIN assessment classified 18 in-vitro studies as having a medium risk of bias and four as having a high risk of bias; no study met the threshold for low risk of bias. Frequent methodological limitations included absent sample-size calculations, incomplete sampling descriptions, limited reporting of randomization and blinding, and inadequate reporting of operator or assessor calibration. Cytotoxicity findings were generally favorable under standard laboratory conditions, although reduced cell viability occurred with selected materials, concentrated extracts, or prolonged exposure. Evidence regarding BPA was limited, while other chemical leachables and microplastic release remained emerging concerns. Several quantitative outcomes showed high or extreme heterogeneity. Current evidence does not establish a universally superior clear aligner material. Material behavior and safety appear dependent on polymer composition, manufacturing method, thickness, post-processing, aging, and testing conditions. Because the evidence was predominantly laboratory-based, frequently at medium or high risk of bias, and methodologically heterogeneous, pooled estimates should not be translated directly into clinical material-selection or wear-schedule recommendations. Standardized laboratory methods and prospective clinical validation are required.