Neutrophil Extracellular Traps in Wound Healing of Diabetes: Mechanisms, Inducers, and Therapeutic Implications

Wound healing damage, especially diabetic foot ulcer (DFU), is a serious complication of diabetes mellitus (DM). New evidence shows that neutrophil extracellular traps (NETs) are the key factor of this pathology. This review summarizes the literature from 2015 to 2024 to clarify the mechanism of NETs and its harmful effects on diabetes wounds. We have provided a detailed introduction to common in vitro NETs inducers such as phorbol 12-myristate 13-acetate (PMA), lipopolysaccharide (LPS), and calcium ionophore, as well as core protein markers such as citrullinated histone H3 (CitH3), myeloperoxidase (MPO), and neutrophil elastase (NE). Importantly, evidence from animal models and human patients suggests that sustained NETs maintain inflammation, hinder angiogenesis, and delay tissue repair. Finally, we explored promising clinical therapeutic strategies that promote healing by targeting NETs, such as DNase I degradation and inhibition of specific signaling pathways, highlighting the potential of NETs inhibition strategies in improving diabetic wound care.