Abstract Diabetic wound healing is a common yet challenging problem in clinical practice that involves complex pathophysiological processes and frequently progresses to chronic nonhealing wounds, imposing substantial burdens on both healthcare systems and patients while markedly decreasing quality of life. Persistent inflammatory responses represent a fundamental pathological feature of this condition. Accumulating evidence highlights the key role of neutrophil extracellular traps (NETs) in the chronic inflammatory response characteristic of diabetic wounds. As components of the innate immune system, NETs play pivotal roles in both host defence and tissue repair. NETosis is currently classified as vital NETosis or lytic NETosis. In this review, we synthesise existing evidence on the mechanistic heterogeneity of NETosis and further refine lytic NETosis subtypes on the basis of distinct molecular mechanisms and temporal dynamics—namely, NOX2-dependent classical lytic NETosis and mitochondrial ROS-driven rapid lytic NETosis. We also highlight the functional outcomes of NETs in response to specific stimuli within the diabetic wound milieu. Therapeutic strategies targeting NET formation, degradation, or neutralisation have shown considerable promise in preclinical studies; however, their clinical translation will require standardised biomarkers for NET quantification, localised delivery approaches to minimise systemic immunosuppression, and biomarker-guided frameworks to balance the risk of infection against healing benefits.
Hu et al. (Tue,) studied this question.