Research advances on the targeted programmed cell death regulatory network for treatment of refractory diabetic wounds

Refractory diabetic wounds are severe complications of diabetes mellitus, for which conventional treatments yield limited efficacy. Recent studies have demonstrated that the core pathogenesis lies in the dysregulation of the programmed cell death regulatory network induced by the hyperglycemic microenvironment. Specifically, excessive activation of lytic cell death such as necroptosis, ferroptosis, and pyroptosis drives persistent inflammation; while impairment of non-lytic cell death including apoptosis and cytoprotective autophagy as well as efferocytosis dysfunction results in impaired initiation of the inflammation resolution program. Distinct cell death pathways form a dynamic network through shared regulatory hubs and downstream signaling crosstalk, ultimately locking the wound in a vicious cycle of "cell death—inflammation—repair impairment". This review systematically elaborates on the dysregulation characteristics and interaction mechanisms of the programmed cell death regulatory network in diabetic wounds, and discusses the application prospects of combination therapies and precision stratified treatment.