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To address these challenges, this study developed an injectable hydrogel based on covalent cross\u2010linking between polyethylene glycol derivatives and \u03b5\u2010polylysine. This hydrogel is further loaded with recombinant Milk fat globule\u2010epidermal growth factor\u2010VIII (rMFG\u2010E8) and ferulic acid (FA)\u2010loaded mesoporous manganese dioxide (HM\u2010FA), forming a \u201csingle application, multiple benefits\u201d platform. The hydrogel effectively inhibited planktonic bacteria and controlled wound infection owing to the inherent antibacterial activity of \u03b5\u2010polylysine. Under the acidic microenvironment of diabetic ulcers, the hydrogel gradually degraded and released HM\u2010FA, which scavenged excess ROS and continuously generated oxygen via, thereby alleviating local hypoxia and oxidative stress and reducing inflammatory responses. Subsequently, FA released from the further disintegration of HM\u2010FA acted synergistically with rMFG\u2010E8 to activate the PI3K\/Akt signaling pathway, promoting angiogenesis and tissue regeneration. In vivo experiments demonstrated that the hydrogel exhibited good biocompatibility, significantly suppressed inflammatory responses, and accelerated wound closure in a diabetic ulcer mouse model. In summary, the integrated treatment strategy proposed in this study significantly simplifies clinical procedures and shows promising potential for translational application in diabetic ulcer therapy.<\/jats:p>","DOI":"10.1002\/adhm.202503908","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T07:54:33Z","timestamp":1762847673000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Multi\u2010Modal Therapy for Diabetic Ulcers: A Hydrogel Platform Combining Antibacterial, Oxygenating, ROS\u2010Scavenging, and Pro\u2010Healing Functions"],"prefix":"10.1002","volume":"15","author":[{"given":"Yang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital of Anhui Medical University Hefei Anhui 230601 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of thyroid gland Thyroid Surgery Department of Binzhou People's Hospital Binzhou Shandong 256600 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhennan","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital of Anhui Medical University Hefei Anhui 230601 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital of Anhui Medical University Hefei Anhui 230601 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital of Anhui Medical University Hefei Anhui 230601 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital of Anhui Medical University Hefei Anhui 230601 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyuan","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital of Anhui Medical University Hefei Anhui 230601 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjuan","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Life Sciences Anhui Medical University Hefei Anhui 230032 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"He","sequence":"additional","affiliation":[{"name":"School of Life Sciences Anhui Medical University Hefei Anhui 230032 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3687-1986","authenticated-orcid":false,"given":"Fei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital of Anhui Medical University Hefei Anhui 230601 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2024.12.006"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/iwj.14931"},{"key":"e_1_2_8_3_1","author":"Yen F.\u2010S.","year":"2025","journal-title":"Thromb. 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