Cytotoxic effects of glass ionomer cements modified by metallic agents: A systematic review and meta-analysis

OBJECTIVES: This systematic review and meta-analysis (SRM) aimed to assess the effect of incorporating metallic agents into glass ionomer cements on cytotoxicity. DATA SOURCES: Following PRISMA guidelines, a systematic search of PubMed (MEDLINE), Scopus, Embase, Library Cochrane and Web of Science was performed to identify eligible studies published up to February 1, 2026. STUDY SELECTION: The eligibility criteria included in vitro studies. The data were analyzed using RevMan software, and bias risk was assessed with the Joanna Briggs Institute's Checklist for in vitro studies. RESULTS: Out of 924-screened records, 13 studies were included. Results showed that the incorporation of metallic agents such as silver, zinc oxide, titanium dioxide, and magnesium carbonate apatite did not significantly compromise the cytocompatibility of glass ionomer cements. Quantitative analyses demonstrated that cell viability of pulp cells and fibroblasts remained comparable to control groups, indicating that these modifications maintain baseline cytotoxicity profiles while potentially providing additional functional properties. The meta-analysis showed that metallic agent-modified glass ionomer cements did not affect the viability of pulp cells or fibroblasts at any of the evaluated time points, indicating that these modifications preserve baseline cytocompatibility. The studies showed a low risk of bias. CONCLUSIONS: The available evidence indicates that the incorporation of metallic agents into glass ionomer cements generally preserves cytocompatibility, with most in vitro studies reporting no significant cytotoxic effects. Cytotoxic responses are influenced by the type and concentration of the metallic additive. Nevertheless, the predominance of laboratory-based evidence highlights the need for well-designed in vivo studies to confirm biological safety and support the translational potential of these modified materials. CLINICAL RELEVANCE: Glass ionomer cements modified with metallic agents show favorable cytocompatibility in vitro when proper formulation parameters are followed. Concentration-dependent biological effects highlight the need for careful material design. These findings support further research on metal-modified glass ionomer cements as restorative materials that maintain biocompatibility while improving physicomechanical properties.