2.2.1.1 The mechanism of skin wound healing
Sophisticated and consecutive wound healing process starts immediately after the skin is damaged（physical，chemical and photo-thermal damage）.This process includes four stages：hemostatic phase，inflammation phase，proliferation phase and maturation/reconstruction phase（Figure 2-5）.It involves a variety of cytokines，signal pathways and growth factors，which promote the skin wound healing collaboratively.
1.Hemostatic phase
Blood vessels contracted and exogenous coagulation system are activated promptly after the skin is damaged.The secreted thrombin promote fibrinogen transforming into fibrin.Red blood cells，platelets and crosslinking collagen fibers aggregate in the local wound site and block the impaired vessel via the formation of blood clots.Then the aggregated platelets are activated and induced the production of glycoproteins and various growth factors.Glycoproteins can promote the formation of thrombus，exerting hemostatic effect.Epidermal growth factor（EGF），transforming growth factor-β（TGF-β），fibroblast growth factor（FGF）and platelet derived growth factor（PDGF）stimulate fibroblasts to produce more collagen and elastin.
2.Inflammation phase
As the vasodilation of blood vessels and increased vascular permeability，a large number of white blood cells and macrophages infiltrate into the wound site and remove necrotic tissue，preventing wound infection.At first，neutrophils migrate into the wound site，remove microorganisms by phagocytosis and degrade necrotic tissue by protease.Subsequently，macrophage infiltrates into the wound site and remove the bacteria and contaminants.A large variety of interleukins（ILs），growth factors and tumor necrosis factor（TNF）participate in the inflammation phase of skin wound healing process.(https://www.daowen.com)
3.Proliferation phase
Granulation tissue consists of fibroblasts，newborn thin-walled capillary and inflammatory cells.Macrophages secrete TGF-β and PDGF to induce the proliferation of fibroblasts and the production of typeⅢ collagen.Endothelial cells proliferate on the collagen and promote the formation of microvessels.Fibroblasts synthesize and secrete the type Ⅰ and type Ⅲ collagen，of which type Ⅲ collagen is prominent.The migration of fibroblasts is mediated by matrix metalloproteinases（MMPs），growth factors and interleukins.Studies have shown that fat cells can migrate into the surrounding wound sites，induce epidermal cells covering wounds，and promote wound healing.
4.Maturation/reconstruction phase
Keratinocytes，fibroblasts and macrophages secrete various kinds of matrix degrading enzymes to degrade the excessive extracellular matrix.Type Ⅲ collagen is replaced by the more intensive type Ⅰ collagen.During the maturation/reconstruction phase，the skin tissue thickened and the skin barrier function is recovered.This stage could last for 2 years or more.