TITLE:
Ferroptosis in Diabetic Wound Repair: Cell-Specific Mechanisms, Therapeutic Targeting, and Translational Barriers
AUTHORS:
Yongfu Chen, Haidong Zhou, Pengyuan He, Wenbo Li, Runze Wu, Jiahui Wang, Dingpeng Ban, Jihua Wei
KEYWORDS:
Diabetic Foot Ulcer, Ferroptosis, Lipid Peroxidation, Iron Homeostasis, Wound Healing, Translational Medicine
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.14 No.9,
September
16,
2026
ABSTRACT: Diabetic wounds, particularly diabetic foot ulcers (DFUs), are sustained by hyperglycemia, ischemia, infection, persistent inflammation, oxidative stress, defective angiogenesis and matrix failure. Ferroptosis—an iron-dependent regulated cell death driven by phospholipid peroxidation—provides a mechanistic link among these abnormalities. A targeted PubMed search through 10 July 2026, supplemented by reference-list screening, identified mechanistic, preclinical and clinical studies relevant to ferroptosis in diabetic wound repair. Evidence was classified as oxidative-injury-associated or ferroptosis-causal according to whether compatible iron/lipid-peroxidation findings were accompanied by ferroptosis-directed rescue, genetic perturbation or orthogonal validation. Iron dyshomeostasis, impaired SLC7A11-GSH-GPX4 activity, altered NRF2 signaling, mitochondrial stress, ferritinophagy, endoplasmic reticulum stress and neutrophil extracellular traps can lower the ferroptotic threshold in macrophages, keratinocytes, fibroblasts and endothelial cells. Current interventions include natural compounds, traditional formulations, extracellular vesicles, platelet-rich plasma, nanozymes and hydrogel-based delivery systems. The evidence supports cell- and stage-specific modulation rather than blanket inhibition: reparative cells generally require protection, whereas selective induction in defined pro-inflammatory or senescent states remains preclinical. The only prospective DFU biomarker evidence is observational, and no controlled DFU treatment study has demonstrated clinical efficacy of a ferroptosis-targeted intervention. Translation is limited by non-specific biomarkers, incomplete causal validation, simplified models and uncertain long-term material safety. Progress requires orthogonal ferroptosis assays, clinically realistic models, human tissue validation and prospective outcome-linked studies.