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This systematic review, conducted according to PRISMA 2020 guidelines, summarised evidence from 34 studies published between 2020 and 2025 on immunomodulatory tissue\u2010engineering strategies for DFU management. Most studies used STZ\u2010induced or db\/db diabetic mouse models; only two included human data. Across natural polymer hydrogels, electrospun nanofibers, microneedles, and hybrid antimicrobial dressings, a consistent mechanistic theme emerged: promotion of macrophage polarisation from pro\u2010inflammatory M1 to pro\u2010regenerative M2. Cytokine delivery, exosome\u2010based therapies, ROS\u2010targeted nanozymes, metabolic reprogramming, and electrical or microcurrent stimulation resolved chronic inflammation, enhanced angiogenesis, and accelerated wound closure. Key signalling pathways (JAK\/STAT, NF\u2010\u03baB, HMGB1\u2013RAGE, HIF\u20101\u03b1) represent promising molecular targets. Despite encouraging preclinical outcomes, heterogeneity and limited human studies underscore the need for well\u2010powered, long\u2010term clinical trials and biomarker\u2010driven personalised immunomodulatory strategies.<\/jats:p>","DOI":"10.1111\/wrr.70149","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T11:32:04Z","timestamp":1774438324000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Immunomodulatory Tissue\u2010Engineering Strategies for Diabetic Foot Ulcer Management: A Systematic Review"],"prefix":"10.1111","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4352-1124","authenticated-orcid":false,"given":"G\u00f6zde","family":"\u00d6zsezer","sequence":"first","affiliation":[{"name":"Faculty of Health Sciences, Department of Public Health Nursing \u00c7anakkale Onsekiz Mart University  \u00c7anakkale Turkey"},{"name":"Regenerative Biomaterials 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