{
  "abstract": "Diabetic foot ulcers are chronic wounds characterized by persistent inflammation, defective inflammatory resolution, and impaired tissue repair. Macrophages coordinate host defense, efferocytosis, inflammatory resolution, angiogenesis, and tissue reconstruction, but the diabetic wound environment can impair their adaptation, function, and survival. Ferroptosis, an iron-dependent form of regulated cell death driven by phospholipid peroxidation, has emerged as a potential mechanism linking diabetic wound stress to impaired macrophage function and survival. This review evaluates current evidence for ferroptosis in diabetic foot ulcers and distinguishes evidence from markers and pharmacological rescue obtained at the level of whole wounds from direct evidence in macrophages. We examine how altered iron handling and ferritinophagy, lipid remodeling, impaired glutathione peroxidase 4 activity and complementary antioxidant defenses, inflammatory and immunometabolic stress, and macrophage state may increase ferroptotic susceptibility. We then consider the potential consequences for macrophage functions required for repair, efferocytosis and inflammatory resolution, and support for fibroblasts, endothelial cells, and keratinocytes across wound regions and phases. Current studies support ferroptotic stress as a therapeutically modifiable process in diabetic wounds, but direct in situ evidence of ferroptotic stress or death in defined macrophage populations within human diabetic foot ulcers remains limited. Its biological consequences are also likely to vary according to macrophage state and wound phase. Accordingly, therapeutic strategies should avoid indiscriminate suppression or induction of ferroptosis and instead preserve macrophage functions required for antimicrobial defense, inflammatory resolution, and tissue repair while controlling excessive iron accumulation and phospholipid peroxidation. Spatially resolved biochemical analyses, longitudinal sampling, and functional perturbation in defined macrophage populations will be needed to establish causality and guide treatment according to macrophage state and wound phase.",
  "abstract_shown": true,
  "affiliations": [
    "Heilongjiang University of Chinese Medicine",
    "Department of Peripheral Vascular Disease, Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine",
    "Department of Peripheral Vascular Disease, The Second Affiliated Hospital of Henan University of Chinese Medicine",
    "Liaoning University of Chinese Medicine Xinglin College",
    "Department of General Surgery, The Third Affiliated Hospital of Heilongjiang University of Chinese Medicine",
    "Department of Peripheral Vascular Disease, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jingyu Lang"
    },
    {
      "affs": [
        1
      ],
      "name": "Haiyan Zhao"
    },
    {
      "affs": [
        2
      ],
      "name": "Nian Zhou"
    },
    {
      "affs": [
        3
      ],
      "name": "Yihe Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Yifu Tie"
    },
    {
      "affs": [
        4
      ],
      "name": "Chunyu Yang"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Gang Zhao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/emzg0chhsadmn.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1952662",
  "fulltext_url": null,
  "id": "emzg0chhsadmn",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1952662/full",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2742|Wound Healing and Treatments"
    ]
  ],
  "openalex": "W7223697706",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1952662/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-26",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/emzg0chhsadmn.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1952662",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1952662/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "issn:1664-3224",
      "subfield": "immunology"
    }
  ],
  "title": "Macrophage ferroptosis in diabetic foot ulcers: current evidence, mechanisms, and therapeutic implications",
  "title_text": "Macrophage ferroptosis in diabetic foot ulcers: current evidence, mechanisms, and therapeutic implications",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:17Z",
  "url": "https://research.draconitic.com/paper/emzg0chhsadmn",
  "venue": "Frontiers in Immunology",
  "versions": []
}