Engineering fast-acting anti-itching multifunctional dressing with quercetin-CD-MOF for atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by susceptibility to infection and recurrent pruritus. Clinical treatment often focuses solely on skin lesions while neglecting direct control of pruritus symptoms. Herein, this study reports a novel powdered dressing (Que@CD@PH) that integrates in situ gelation, wet adhesion, and burst release of drugs for the treatment of AD. This dressing is composed of ε-polylysine, NHS-esterified hyaluronic acid, and quercetin-loaded water-soluble cyclodextrin metal-organic frameworks (Que@CD). Upon application to moist skin, it rapidly forms an adhesive gel, providing physical protection. Under the action of water molecules, the metal-organic framework structure of Que@CD rapidly decomposes, releasing quercetin to exert antipruritic effects. Meanwhile, Que@CD exhibits excellent biocompatibility and can directly scavenge reactive oxygen species at the lesion site while inhibiting the proliferation of AD-susceptible pathogenic bacteria such as Staphylococcus aureus (with a clearance ratio exceeding 99%), thereby alleviating skin inflammation through two key pathological mechanisms-oxidative stress and bacterial infection-and laying the foundation for subsequent remodeling of the immune microenvironment. Further mechanistic studies revealed that the dressing promotes macrophage polarization from the M1 to the M2 phenotype through activation of the AMPK/NRF2/HO-1 pathway, thereby exerting immunomodulatory effects. In a DNCB-induced mouse model of AD, Que@CD@PH alleviated dermatitis symptoms, reduced scratching frequency by 71.4%, lowered IgE (Immunoglobulin E) levels by 45.6%, and suppressed Th2-type inflammatory cytokines. This work presents a translatable strategy for managing AD through a biocompatible dressing with synergistic antipruritic, antibacterial, and immunomodulatory functions.