On-demand amorphous calcium phosphate-mediated regeneration of dentin and enamel using ion-regulated hydroxypropyl methylcellulose and carboxymethyl chitosan hydrogels.

This study presents an innovative heteropolysaccharide hydrogel system engineered through the synergistic combination of hydroxypropyl methylcellulose‑calcium (HPMC-Ca) and carboxymethyl chitosan-phosphate (CMCS-P). This dual-network hydrogel uniquely leverages the complementary physicochemical properties of both polysaccharides to achieve simultaneous biomimetic mineralization of enamel and dentin-addressing a long-standing challenge in restorative dentistry. The hydrophobic domains of HPMC-Ca facilitate sustained calcium ion release, establishing a stable mineralization reservoir, while CMCS-P provides phosphate sources that interact with calcium to form mineralization-competent amorphous calcium phosphate (ACP). Furthermore, the hydrogel acts as a biomimetic template, guiding dentin remineralization and enabling epitaxial growth of enamel-like structures. Advanced characterization techniques-including FTIR, Cryo-TEM, molecular simulations, and nanoindentation-collectively demonstrate that molecular-level interactions between HPMC and CMCS critically regulate the mineralization process. Remarkably, the system restores mechanical properties comparable to natural tooth tissues within just 7 days, confirming effective regeneration of both dentin and enamel. Beyond elucidating fundamental mechanisms of polysaccharide-mediated biomineralization, this work also provides new ideas for the research and development of dental caries prevention and restoration materials.