Mechanisms of impaired diabetic wound healing. The normal wound-healing process is initiated by the integration of multiple intercellular signals (cytokines and chemokines) released by keratinocytes, fibroblasts, endothelial cells, macrophages, platelets, etc. In diabetes, inflammatory cytokines and chemokines are elevated, such as TNF-α, IL-1, IL-6, CCL2, CCL3, CCL4, CXCL1, CXCL5, and CXCL8. Cellular processes affected by diabetes include abnormal keratinocyte and fibroblast migration, proliferation, and enhanced apoptosis; abnormal macrophage polarization (increased proinflammatory M1 macrophages and decreased anti-inflammatory M2 macrophages); impaired recruitment of mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs), and decreased vascularization.