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To address these challenges, herein we developed a novel tri\u2010layered scaffold to provide multi\u2010functional therapeutic support. The bottom poly (lactic\u2010co\u2010glycolic acid) (PLGA) fibrous layer contains doxycycline loaded CuBDC nanosheets for rapid antibacterial action. The porous PLGA\/gelatin middle layer offers mechanical support and \u03b3\u2010tocotrienol loaded ZIF\u20108 nanocrystals mitigates oxidative stress in the wound. The PLGA top sealing fibrous layer delivers insulin and Transforming growth factor beta (TGF\u2010\u03b21) from Zeolitic Imidazolate Framework\u20108 (ZIF\u20108) nanocrystals to promote epithelialization and modulate inflammation. Comprehensive in vitro and in vivo evaluations demonstrated that the scaffold effectively filled deep wounds, reduced bacterial load, controlled inflammation, and accelerated the tissue regeneration. Histopathological analyses showed enhanced epithelialization and partial granulation tissue remodeling. Biochemical assays indicated an increase in glutathione peroxidase (GPx) activity and a reduction in lipid peroxidation. Gene expression analysis revealed decreased levels of the pro\u2010inflammatory TNF\u2010\u03b1 and increased levels of the anti\u2010inflammatory IL\u201010, facilitating the transition to the proliferative phase. This multi\u2010layered composite scaffold, with its antimicrobial, antioxidant, and anti\u2010inflammatory activities, controlled release capabilities, presents a promising solution the healing process of deep, infected diabetic wounds.<\/jats:p>","DOI":"10.1002\/adhm.202500356","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T01:04:07Z","timestamp":1745283847000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Tri\u2010Layered Bioactive Cutaneous Scaffold with Integrated Bioactive Metal Organic Frameworks to Promote Full\u2010Thickness Infected Diabetic Wound Healing: Multifaceted Therapeutic Strategies"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9301-8928","authenticated-orcid":false,"given":"Ayse Gunyakti","family":"Mujtaba","sequence":"first","affiliation":[{"name":"Biotechnology Institute Ankara University  G\u00fcm\u00fc\u015fdere 60. 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