Halogen‐Engineered Covalent Organic Framework Hydrogel for Efficient Photocatalytic Hydrogen Release in Atopic Dermatitis Therapy

ABSTRACT Atopic dermatitis (AD) is a chronic inflammatory skin disease with intractable pruritus and barrier disruption. Current therapies offer limited efficacy and are associated with adverse effects, highlighting the urgent need for safer alternatives. Hydrogen (H 2 ) shows anti‐inflammatory and antioxidant potential, but effective topical delivery remains challenging. Herein, we report a halogen‐modulated covalent organic framework (COF) hydrogel that integrates a “halogen‐engineered internal electric field” strategy to achieve enhanced photocatalytic H 2 production with sustained release. Systematic substitution of halogens in an imine‐linked pyrene COF reveals that fluorine, due to its highest electronegativity, imparts the largest dipole moment and strongest built‐in field, which substantially facilitates photogenerated charge separation and prolongs carrier lifetime, affording an exceptional visible‐light H 2 evolution rate of 8.25 mmol g − 1 h − 1 . In an MC903‐induced AD mouse model, topical application of this H 2 COF hydrogel markedly alleviates lesion severity and attenuates scratching and anxiety‐like behaviors. Mechanistically, the hydrogel restores redox homeostasis, reduces NF‐κB‐associated inflammation, and modulates NRF2/HO‐1 signaling, supported by biochemical and immunofluorescence protein‐level evidence, consistent with transcriptomic reversal of AD‐related pathways. This hydrogen‑releasing system offers a safe, convenient, and translatable H 2 therapy for AD and other chronic inflammatory skin diseases.