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Oxidative stress is a key factor exacerbating inflammation and itching. To address the challenge that existing local therapies struggle to sustainably regulate redox balance in the microenvironment, this study cross-linked carboxymethylated housefly chitosan (CMCS) with oxidized fucoidan (OFUA) to form an imine-linked hydrogel (C\/O) via a Schiff base reaction and loaded it with a functionalized nanoparticle. This nanoparticle was a cyclodextrin metal\u2013organic framework (P-M@CA) loaded with chlorogenic acid (CA) and surface-modified with polydopamine (PDA). A composite hydrogel system (C\/O\/P) for AD treatment was successfully constructed. This system exhibited strong antioxidant activity both in vitro and in vivo and effectively alleviated oxidative stress associated with AD. The C\/O\/P hydrogel dramatically decreased epidermal thickening, inhibited mast cell infiltration, downregulated the key inflammatory factor thymic stromal lymphopoietin (TSLP), and lowered serum immunoglobulin E (IgE) levels in an AD mouse model established by induction with 1-chloro-2,4-dinitrobenzene (DNCB). In summary, C\/O\/P hydrogels effectively clear reactive oxygen species and regulate the oxidative stress microenvironment, offering a promising local delivery strategy for AD treatment.<\/jats:p>","DOI":"10.1021\/acsami.6c17073","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T19:02:16Z","timestamp":1789585336000},"page":"52219-52237","source":"Crossref","is-referenced-by-count":0,"title":["Sprayable Integrated Hydrogel for Synergistic Alleviation of Oxidative Stress in Atopic Dermatitis Treatment"],"prefix":"10.1021","volume":"18","author":[{"given":"Shuang","family":"Liu","sequence":"first","affiliation":[{"name":"Chengdu University of Traditional Chinese Medicine , , ,","place":["Chengdu, China, 611137"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Chengdu University of Traditional Chinese Medicine , , ,","place":["Chengdu, China, 611137"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huacheng","family":"Tang","sequence":"additional","affiliation":[{"name":"Chengdu University of Traditional Chinese Medicine , , ,","place":["Chengdu, China, 611137"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Chengdu University of Traditional Chinese Medicine , , ,","place":["Chengdu, China, 611137"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxi","family":"Li","sequence":"additional","affiliation":[{"name":"Chengdu University of Traditional Chinese Medicine , , ,","place":["Chengdu, China, 611137"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Duan","sequence":"additional","affiliation":[{"name":"Chengdu University of Traditional Chinese Medicine , , ,","place":["Chengdu, China, 611137"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxuan","family":"He","sequence":"additional","affiliation":[{"name":"Chengdu University of Traditional Chinese Medicine , , ,","place":["Chengdu, China, 611137"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengxin","family":"Su","sequence":"additional","affiliation":[{"name":"Chengdu University of Traditional Chinese Medicine , , ,","place":["Chengdu, China, 611137"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuchen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Southwest University , , ,","place":["Chongqing, China, 400715"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Huang","sequence":"additional","affiliation":[{"name":"Chengdu University of Traditional Chinese Medicine , , ,","place":["Chengdu, China, 611137"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomin","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Plastic and Cosmetic Dermatology, Deyang People's Hospital , ,","place":["Deyang, China, 6l8000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1625-8682","authenticated-orcid":true,"given":"Jun","family":"Lu","sequence":"additional","affiliation":[{"name":"Chengdu University of Traditional Chinese Medicine , , ,","place":["Chengdu, China, 611137"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4982-1056","authenticated-orcid":true,"given":"Xiaoli","family":"Pan","sequence":"additional","affiliation":[{"name":"Chengdu University of Traditional Chinese Medicine , , ,","place":["Chengdu, China, 611137"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"2026093001073714800_cit1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23105318","article-title":"Revisiting the Roles of Filaggrin in Atopic Dermatitis","volume":"23","author":"Moosbrugger-Martinz","year":"2022","journal-title":"Int. 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