A Starch Gum with a Multi‐Cascade Enzymatic Reaction Targeting Dental Caries Biofilm Eradication and Enamel Regeneration

The progression of dental caries is exacerbated by the presence of bacterial biofilms on carious enamel surfaces, which inhibit remineralization and exacerbate caries. Existing caries treatment protocols are often complex and costly. To simultaneously eradicate caries-associated biofilms and repair demineralized enamel, this study develope a starch-based gum containing calcium carbonate nanoparticles loaded with L-arginine (CaCO₃@L-Arg) and glucose oxidase (GOx). The gum can absorb water and swell into a gel. Due to the hydrogen bonding and adhesive properties of gelatinized starch, the starch gel can be freely shaped to fill and adhere to irregular carious cavities. In particular, under the weak acid microenvironment of caries biofilms and the enzymatic action of salivary amylase (Amy), the gel degrades within 3-5 hours, releasing GOx and L-Arg. These components trigger a dual enzyme (Amy and GOx) mediated multi-cascade reaction (starch → glucose → H₂O₂ → NO) that effectively disrupts biofilms formed by Streptococcus mutans (S. mutans) and other cariogenic bacteria. At the same time, calcium and phosphate ions released from the gel use the starch as a template to form calcium phosphate in situ, promoting enamel remineralization. This dual-functional system effectively eradicates interdental biofilms and restores enamel, representing a promising strategy for the treatment of early caries.