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This study investigated the effects of a glycol chitosan-silk fibroin hydrogel loaded with Ephrin-B2 (GCS-SF-B2 Gel) on the healing of full-thickness skin wounds in a diabetic mouse model. We prepared the hydrogel by mixing glycol chitosan and silk fibroin solutions, followed by lyophilization and adsorption of Ephrin-B2. The GCS-SF-B2 Gel exhibited a porous structure with a swelling capacity of up to 1600% and a moisturizing duration of up to 12\u00a0h. In vitro assays demonstrated that the hydrogel significantly promoted the proliferation and migration of NIH 3T3 cells. In a diabetic mouse model with full-thickness skin defects, the GCS-SF-B2 Gel demonstrated superior therapeutic efficacy compared to control, evidenced by macroscopic healing, increased fibroblast accumulation, improved collagen deposition, and significant angiogenesis at the wound site. These findings suggest that GCS-SF-B2 Gel is a promising candidate for promoting the healing of refractory diabetic wounds.<\/jats:p>","DOI":"10.1038\/s41598-026-60669-6","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T19:24:54Z","timestamp":1783020294000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Application of ephrin-B2 loaded glycol chitosan-silk fibroin hydrogel in the treatment of diabetic refractory wounds"],"prefix":"10.1038","volume":"16","author":[{"given":"Baosheng","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxing","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanhada","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuling","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enhe","family":"Jirigala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"60669_CR1","doi-asserted-by":"publisher","first-page":"176089","DOI":"10.1016\/j.ejphar.2023.176089","volume":"960","author":"UM Parmar","year":"2023","unstructured":"Parmar, U. 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