Activation of Inflammatory and Apoptosis Pathways on Human Gingival Fibroblasts Exposed to Dental Resin Composites

The use of dental composite resins has significantly increased over recent years, thanks to their esthetics and mechanical features, despite some doubts being raised about their biocompatibility. Residual methacrylate can be eluted from bulk composites, and its amount may significantly increase over time, leading to cytotoxic effects that can involve several inflammatory patterns. The aim of this in vitro study was to evaluate the activation of the inflammatory pathway NFκB p65/MyD88/NALP3 and the apoptosis pathway of BCL-2/BAX/Caspase-3 (CASP-3) expression on human gingival fibroblasts (hGFs) after 24 h and 1-week exposure to the eluates of three heat-cured dental composite resins: GrandioSO, VOCO (GR); Enamel Plus HRi Biofunction, Micerium (BF); and Filtek universal restorative, 3M (FU). The results highlighted that NFκB p65/MyD88/NALP3 was activated after resin exposure in a time-dependent manner. Moreover, immunofluorescence and gene expression analyses showed that pro-apoptotic markers CASP-3 and BAX were elevated, while anti-apoptotic protein BCL-2 was suppressed in hGFs after dental resin exposure. The present in vitro study analyzed mechanisms related to cytotoxicity and apoptosis, suggesting ways to limit composite cytotoxicity through advancements in material technology. The activation of inflammation and apoptotic pathways appeared to be material-dependent, and was less pronounced with BF and FU, which could hypothetically indicate them being a safer clinical choice to preserve periodontal health in daily dental practice.