In situ Synthesis of Amorphous Fluorinated Calcium Phosphate Nanoparticles via a Dual-Component Hydrogel for Biomimetic Tooth Remineralization.

OBJECTIVE: To report the in situ synthesis of amorphous fluorinated calcium phosphate (AFCP) nanoparticles within a dual-component hydrogel and evaluate their efficacy for enamel remineralization and dentinal tubules (DTs) occlusion. MATERIALS AND METHODS: The AFCP hydrogel was constructed using hydroxypropyl methylcellulose (HPMC) and carboxymethyl chitosan (CMC) to stabilize calcium, phosphate, and fluoride ions in a metastable amorphous state. Physicochemical characterization was performed by FTIR, XRD, TEM, and SEM-EDX. Biocompatibility was assessed via CCK-8 assays and oral mucosal irritation test. Demineralized enamel and dentin specimens (n=8) were treated with deionized water, fluoride (NaF, 2000 ppm F), 10% CPP-ACP with 900 ppm F (GC Tooth Mousse Plus, Japan), or AFCP hydrogel, and immersed in artificial saliva for 7 days. Remineralization was evaluated by SEM, XRD, and nanoindentation, followed by in vivo validation in a rabbit model. RESULTS: The hydrogel generated AFCP nanoparticles (30-80 nm) that remained amorphous in artificial saliva for over 2 hours before crystallizing into hydroxyapatite. The hydrogel exhibited negligible cytotoxicity and no oral mucosal irritation. After 7 days, the AFCP hydrogel induced dense mineral deposition that completely occluded exposed DTs and formed a ~32 µm remineralized layer on acid-etched enamel, substantially outperforming fluoride and CPP-ACP + NaF. XRD confirmed the newly formed mineral as hydroxyapatite-like. Treatment with the AFCP hydrogel restored the mechanical properties of enamel and dentin to near-physiological levels, achieving the greatest recovery among the four groups (P < 0.05). In vivo results further validated its remineralization and tubule-occluding efficacy. CONCLUSION: The AFCP hydrogel functions as an exogenous mineral reservoir, enabling sustained ion release or direct transformation into hydroxyapatite for in situ enamel remineralization and DTs occlusion. This non-invasive strategy offers a promising therapeutic approach for early caries and dentin hypersensitivity.