Bioactive performance of resin-modified glass ionomer cement functionalized with polyvalent metals and cyclic phosphates: Effects on demineralization resistance and mineralization-related cellular responses

OBJECTIVE: To investigate whether functionalization of a resin-modified glass ionomer cement (RMGIC) with sodium trimetaphosphate (TMP) and stannous chloride (SnCl₂), individually or in combination, affects its resistance to demineralization, cytocompatibility, and mineralization-related cellular responses. METHODS: Six experimental RMGIC formulations were prepared: (1) RMGIC; (2) RMGIC + 14% TMP; (3) RMGIC + 400 ppm SnCl₂; (4) RMGIC + 14%TMP + 400 ppm SnCl₂; (5) RMGIC + 800 ppm SnCl₂; and (6) RMGIC + 14%TMP + 800 ppm SnCl₂. The anti-demineralization effect was evaluated using a pH-cycling model by determining final surface hardness (fSH), percentage of surface hardness loss (%SHL), and integrated subsurface hardness loss (ΔKHN). Biological performance was assessed by cell viability, alkaline phosphatase (ALP) activity, and mineralized nodule formation. RESULTS: The modified RMGIC formulation showed significantly improved anti-demineralization performance compared with the unmodified RMGIC. Formulations containing both additives exhibited higher final surface hardness and lower surface (%SHL) and subsurface (ΔKHN) mineral loss than the unmodified RMGIC (p < 0.05), whereas formulations containing TMP or SnCl₂ alone showed intermediate effects. None of the modifications adversely affected cell viability, with all formulations maintaining viability above 95%. In addition, the combined incorporation of TMP and SnCl₂ significantly increased ALP activity and mineralized nodule formation compared with the unmodified RMGIC (p ≤ 0.0001), indicating enhanced mineralization-related cellular responses. CLINICAL SIGNIFICANCE: Incorporation of TMP and SnCl₂ enhanced RMGIC resistance to demineralization while maintaining cytocompatibility and promoting mineralization-associated responses. This functionalization strategy supports the development of multifunctional restorative materials with improved mineral protection and biological activity beyond the properties of conventional glass ionomer cements.