Polyphenol-functionalized silk fibroin incorporates self-assembled drug delivery platforms for oral ulcers treatment by robust wet adhesion and sustained drug release. International Journal of Biological Macromolecules 2025, 328, 147592.

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Oral ulcers (OU) represent a highly prevalent mucosal disease; however, treatment using existing dressings is often challenging due to insufficient wet adhesion and limited efficacy. In this study, a polyphenol-functionalized silk fibroin (SF) adhesive incorporating a drug delivery platform was developed for the treatment of OU. Silk fibroin (SF) was functionalized with epigallocatechin gallate (EGCG) to form dry granules (termed pwd#ES). Subsequently, drug delivery platforms loaded with dexamethasone (denoted CMC/CS@Ca@Dex) were doped into these granules, resulting in a composite dry granular SF dressing [pwd#ES-(CMC/CS@Ca@Dex)] designed for ulcerated mucosal tissue. The CMC/CS@Ca@Dex platform was prepared by self-assembling chitosan (CS) and carboxymethyl cellulose (CMC) layer-by-layer onto CaCO₃ cores, followed by dexamethasone loading. The resultant composite SF dressing exhibited strong wet tissue adhesion (32.8 kPa), mediated by synergistic interactions within the polyphenol-functionalized SF matrix, alongside excellent reactive oxygen species (ROS) scavenging and bactericidal activity attributed to EGCG. In a mouse model of OU, the pwd#ES-(CMC/CS@Ca@Dex) dressing significantly accelerated healing and promoted faster re-epithelialization. This pwd#ES-(CMC/CS@Ca@Dex) dressing is anticipated to improve the efficiency of OU treatment and inspire the rational design of wet tissue adhesives for the repair of moist tissue defects.