Table I.
Changes in diabetes that affect stages of healing in animal models and patients with diabetes26,27,34,36,231–247
| Alterations in inflammatory phase | Alterations in proliferative phase | Alterations in remodeling phase |
|---|---|---|
| ↑ Levels of proinflammatory cytokines (IL-6, MCP1, TNF-α) | ↓ Fibroblast proliferation and migration | ↑ MMPs |
| ↓ Phagocytosis | ↓ Keratinocyte differentiation and migration | ↓ Collagen and elastin content |
| ↑ NETosis | ↓ Functional levels of growth factors (PDGF, IGF-1, VEGF) | ECM glycation and ↑ crosslinking |
| ↓ Numbers of CD4+ T cells | Impaired angiogenesis | ↓ Levels of TIMPs (MMP inhibitors) |
| ↑ Oxidative stress | Endothelial cell dysfunction | ↑ Presence of nonsolubilized and fragmented ECM fibrils |
| Impaired macrophage polarization (proinflammatory to proreparative phenotype switch) | Pericyte dysfunction | ↓ Wound contraction and wound strengthening |
| Impaired neutrophil function | Mast cell dysfunction | Fibroblast senescence |
Abbreviations: ECM, extracellular matrix; IGF-1, insulin-like growth factor-1; IL-6, interleukin-6; MCP1, monocyte chemoattractant protein-1; MMPs, matrix metalloproteinases; NET, neutrophil extracellular traps; PDGF, platelet-derived growth factor; TIMPs, tissue inhibitors of metalloproteinases; TNF-α, tumor necrosis factor alpha; VEGF, vascular endothelial growth factor.