Epigenetic regulation of inflammation dynamics during wound healing: a subtle yet profound shift in histone modifications.

Wound healing represents a dynamic process centered on the temporally coordinated inflammatory, proliferative, and remodeling phases. The inflammatory response exhibits a double-edged role: a moderate response is essential for normal healing, but excessive or persistent response impedes repair processes. In normal wound healing, histone modifications precisely regulate inflammatory responses from initiation to resolution, mainly manifested through early-stage modulation of NETs and late-stage intervention in macrophage polarization. In chronic non-healing wounds such as diabetic wounds, venous ulcers, and pressure ulcers, the specific pathological microenvironment regulates the inflammatory response of immune cells through various histone modifications, resulting in a greater intensity and longer duration of the inflammation. Herein, we summarize the critical roles of histone modifications in normal and chronic non-healing wounds, highlighting the subtle alterations of histone methylation and acetylation in macrophages that lead to macrophage reprogramming and inflammation regulation, thus providing the promise of precision therapy for chronic non-healing wounds.