{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T05:16:34Z","timestamp":1780118194399,"version":"3.54.0"},"reference-count":55,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100016047","name":"Science Fund of the Republic of Serbia","doi-asserted-by":"crossref","award":["11067"],"award-info":[{"award-number":["11067"]}],"id":[{"id":"10.13039\/501100016047","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Unleashing Nature\u2019s Potential: Using Grape Skin Extract and Sustainable Materials for Advanced Chronic Wound Therapy-GraSP_MAT","award":["14848"],"award-info":[{"award-number":["14848"]}]},{"name":"Ministry of Science, Technological Development, and Innovations Agreements","award":["451-03-137\/2025-03\/200111"],"award-info":[{"award-number":["451-03-137\/2025-03\/200111"]}]},{"name":"Ministry of Science, Technological Development, and Innovations Agreements","award":["451-03-136\/2025-03\/200111"],"award-info":[{"award-number":["451-03-136\/2025-03\/200111"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: This research aims to offer significant insights into the prospective application of bioactive hydrogels composed of alginate, gelatin, and grape skin extract from Serbia (GSE) for treating diabetic wounds, supporting the circular economy and environmental protection. Methods: An acute dermal irritation study was conducted according to OECD guidelines, revealing no visible signs of erythema or edema, confirming the hydrogel\u2019s dermal safety. Afterwards, male Wistar rats were divided into four groups: untreated control (NC), silver sulfadiazine-treated (PC), hydrogel without extract (HG), and hydrogel with GSE (HG + GSE). Wound healing was assessed through a comprehensive approach that included macroscopic wound contraction; biochemical assessment of hydroxyproline content and oxidative stress markers (TBARS, SOD, CAT, GSH); quantification of inflammatory cytokines (TNF-\u03b1, IL-6); and histological examination of skin samples using hematoxylin\u2013eosin (H&amp;E) and Masson\u2019s trichrome staining. Results: Daily HG+GSE application over 15 days accelerated wound closure, reaching 99.3% by day 15, surpassing PC (91.2%) and HG (87.7 \u00b1 2.1%). Hydroxyproline levels followed a treatment-dependent pattern, with HG+GSE achieving the highest values throughout, reaching 6.78 \u00b1 0.1 \u00b5g\/mg dry tissue by day 15\u2014more than double NC. The HG+GSE reduced lipid peroxidation while enhancing enzymatic and non-enzymatic antioxidant defenses and markedly lowered pro-inflammatory cytokine levels, indicating systemic anti-inflammatory activity. Histological analysis revealed faster re-epithelialization, increased collagen deposition, and more organized tissue architecture in the HG+GSE group. These outcomes are attributed to the sustained release of bioactive polyphenols such as naringin, caffeic acid, and epicatechin. Conclusions: Overall, this GSE-based hydrogel presents a multifunctional, biocompatible, sustainable, and effective strategy for diabetic wound care.<\/jats:p>","DOI":"10.3390\/pharmaceutics17111464","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T09:10:45Z","timestamp":1763025045000},"page":"1464","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["From Vineyard to Hydrogel: Antioxidant, Anti-Inflammatory, and Regenerative Potential of Grape Skin Extract in Diabetic Wound Repair"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5388-6085","authenticated-orcid":false,"given":"Jovana","family":"Bradi\u0107","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica, 69, 34000 Kragujevac, Serbia"},{"name":"Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, Zmaj Jovina 30, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3048-4264","authenticated-orcid":false,"given":"Anica","family":"Petrovic","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica, 69, 34000 Kragujevac, Serbia"},{"name":"Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, Zmaj Jovina 30, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9625-0626","authenticated-orcid":false,"given":"Jovana","family":"Joksimovic Jovic","sequence":"additional","affiliation":[{"name":"Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, Zmaj Jovina 30, 34000 Kragujevac, Serbia"},{"name":"Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica, 69, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4932-1288","authenticated-orcid":false,"given":"Marko","family":"Simic","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica, 69, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vesna","family":"Stankovic","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica, 69, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7331-6119","authenticated-orcid":false,"given":"Sanja","family":"Matic","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica, 69, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3810-1694","authenticated-orcid":false,"given":"Marko","family":"Antonijevi\u0107","sequence":"additional","affiliation":[{"name":"Institute for Information Technologies, University of Kragujevac, Jovana Cvijica bb, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2473-9603","authenticated-orcid":false,"given":"Edina","family":"Avdovic","sequence":"additional","affiliation":[{"name":"Institute for Information Technologies, University of Kragujevac, Jovana Cvijica bb, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0071-8376","authenticated-orcid":false,"given":"Vladimir","family":"Jakovljevic","sequence":"additional","affiliation":[{"name":"Center of Excellence for Redox Balance Research in Cardiovascular and 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