Macrophage and Neutrophil Dysfunction in Diabetic Wounds.

Significance: The incidence of diabetes continues to rise throughout the world in an alarming rate. Diabetic patients often develop diabetic foot ulcers (DFUs), many of which do not heal. Non-healing DFUs are a major cause of hospitalization, amputation, and increased morbidity. Understanding the underlying mechanisms of impaired healing in DFU is crucial for its management. Recent Advances: This review focuses on the recent advancements on macrophages and neutrophils in diabetic wounds and DFUs. In particular, we discuss diabetes-induced dysregulations and dysfunctions of macrophages and neutrophils. Critical Issues: It is well established that diabetic wounds are characterized by stalled inflammation that results in impaired healing. Recent findings in the field suggest that dysregulation of macrophages and neutrophils plays a critical role in impaired healing in DFUs. The delineation of mechanisms that restore macrophage and neutrophil function in diabetic wound healing is the focus of intense investigation. Future Directions: The breadth of recently generated knowledge on the activity of macrophages and neutrophils in diabetic wound healing is impressive. Experimental models have delineated pathways that hold promise for the treatment of diabetic wounds and DFUs. These pathways may be useful targets for further clinical investigation.