{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:03:32Z","timestamp":1787321012013,"version":"build-2736575974"},"reference-count":50,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"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":"publisher","award":["U22A20384"],"award-info":[{"award-number":["U22A20384"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82204298"],"award-info":[{"award-number":["82204298"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172086"],"award-info":[{"award-number":["82172086"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["U22A20384"],"award-info":[{"award-number":["U22A20384"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82204298"],"award-info":[{"award-number":["82204298"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82172086"],"award-info":[{"award-number":["82172086"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["2020YFE0201700"],"award-info":[{"award-number":["2020YFE0201700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007620","name":"Educational Department of Liaoning Province","doi-asserted-by":"publisher","award":["LJ232410163022"],"award-info":[{"award-number":["LJ232410163022"]}],"id":[{"id":"10.13039\/501100007620","id-type":"DOI","asserted-by":"publisher"}]},{"award":["LJ232410163022"],"award-info":[{"award-number":["LJ232410163022"]}],"id":[{"id":"https:\/\/ror.org\/0022v2454","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Diabetic foot ulcers (DFUs) are difficult to heal because hyperglycemia-associated pathological exudation, excessive oxidative stress, chronic inflammation, and impaired cellular regeneration jointly maintain a nonhealing wound microenvironment. This study aimed to develop and evaluate a composite hydrogel containing Periplaneta americana (PA) extract and calamine as a Zn2+ source for dynamic modulation of the diabetic wound microenvironment and promotion of tissue repair. Methods: A PA composite hydrogel was prepared and assessed in vitro for reactive oxygen species (ROS)-scavenging activity and effects on fibroblast migration. Therapeutic efficacy was further evaluated in a streptozotocin (STZ)-induced diabetic full-thickness wound model in rats. Wound closure, histological remodeling, oxidative stress markers, inflammatory mediators, growth factors, angiogenesis, and AGEs-RAGE\/NF-\u03baB pathway-related changes were analyzed. Results: The composite hydrogel reduced excessive intracellular ROS and enhanced fibroblast migration in vitro compared with pathological-condition controls. In diabetic rats, topical treatment accelerated macroscopic wound closure and promoted more mature histological repair. Mechanistic analyses showed attenuation of the AGEs-RAGE\/NF-\u03baB signaling axis, accompanied by restoration of superoxide dismutase activity, reduction of malondialdehyde levels, and suppression of TNF-\u03b1-associated inflammatory responses. The improved wound microenvironment was associated with increased expression of platelet-derived growth factor and basic fibroblast growth factor, enhanced cellular proliferation, and increased neovascularization within the wound tissue. Conclusions: The PA composite hydrogel improved diabetic wound healing by concurrently alleviating oxidative and inflammatory barriers and enhancing regenerative signaling. These findings suggest that microenvironment-modulating PA composite hydrogel systems may represent a promising therapeutic strategy for refractory diabetic wounds.<\/jats:p>","DOI":"10.3390\/pharmaceutics18050617","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T16:39:34Z","timestamp":1779295174000},"page":"617","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Synergistic Composite Hydrogel Integrating Periplaneta americana Extract and Calamine for Refractory Diabetic Wound Healing"],"prefix":"10.3390","volume":"18","author":[{"given":"Chenxiao","family":"Chu","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingting","family":"Fan","sequence":"additional","affiliation":[{"name":"School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoman","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongyao","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuying","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Yin","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.7748\/ns.2021.e11709","article-title":"Diabetes mellitus: An overview of the types, symptoms, complications and management","volume":"37","author":"Cloete","year":"2022","journal-title":"Nurs. 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