{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T04:26:36Z","timestamp":1786854396250,"version":"build-2736575974"},"reference-count":51,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82373999"],"award-info":[{"award-number":["82373999"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82373999"],"award-info":[{"award-number":["82373999"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Liaoning BaiQianWan Talents Program","award":["2021A039"],"award-info":[{"award-number":["2021A039"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gels"],"abstract":"<jats:p>(1) Background: Impaired diabetic wound healing stems from systemic dysregulation of the wound-healing cascade under hyperglycemic conditions, producing a disordered microenvironment marked by sustained inflammation, defective angiogenesis, and aberrant extracellular matrix remodeling, multifactorial, multistage pathological interactions demanding multi-target intervention. (2) Methods: We constructed a multifunctional nanocomposite hydrogel dressing (PGAs@CDV) based on a \u201cdrug-carrier integration\u201d strategy, targeting the dysregulated hemostasis, inflammation, and proliferation phases of diabetic wound healing. An amphiphilic micelle carrier (PNO-GA) was synthesized by covalently conjugating Panax notoginseng\u00a0oligosaccharide with gallic acid, loaded with Anemoside B4 to yield drug-loaded nanomicelles (PGAs), embedded into a carboxymethyl chitosan-dopamine-vanillin hydrogel (CDV) matrix to form PGAs@CDV. We then examined how PGAs@CDV affected diabetic wound healing. (3) Results: In vitro, PGAs@CDV enhanced cell migration and angiogenic capacity, exhibited potent antioxidant activity, and promoted M1-to-M2 macrophage polarization. We tested PGAs@CDV in a streptozotocin-induced diabetic mouse wound model. Wounds treated with PGAs@CDV closed faster than those treated with the control, CDV, PNO@CDV, and AB4@CDV. Four readouts tracked this difference: hemostasis was quicker, inflammation was lower, more blood vessels formed, and collagen deposition was higher. At the pathway level, PGAs@CDV suppressed NF-\u03baB signaling and activated PI3K\/AKT\/HIF-1\u03b1. These two arms map onto the anti-inflammatory and pro-angiogenic effects observed above. (4) Conclusions: This nanocomposite hydrogel integrates a bioactive carrier with a therapeutic payload to enable coordinated intervention across multiple phases of diabetic wound repair. By combining structural support with sustained pharmacological activity, it offers a promising strategy for the treatment of chronic diabetic wounds.<\/jats:p>","DOI":"10.3390\/gels12080722","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T08:08:29Z","timestamp":1786694909000},"page":"722","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["AB4-Loaded Nanomicelle Hydrogel Promotes Targeting of the Dysregulated Diabetic Wound Microenvironment via Coordinated Multistage Repair"],"prefix":"10.3390","volume":"12","author":[{"given":"Xue","family":"Shao","sequence":"first","affiliation":[{"name":"School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De-Jing","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Ni","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bang-Yun","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Fei","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Yan","family":"Hua","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Yun","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0608-4669","authenticated-orcid":false,"given":"Xue-Tao","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0140-6736(23)01301-6","article-title":"Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: A systematic analysis for the Global Burden of Disease Study 2021","volume":"402","author":"Ong","year":"2023","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e1801210","DOI":"10.1002\/adhm.201801210","article-title":"Nitric Oxide Therapy for Diabetic Wound Healing","volume":"8","author":"Maloney","year":"2019","journal-title":"Adv. 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