2.2.1.2 The factors affecting skin wound healing
1.Growth factors affecting wound healing process
Growth factors are the bioactive peptides derived from the hematopoietic system，immune system and activated inflammatory cells，which could regulate the proliferation and differentiation of cells and promote metabolism.Growth factors include EGF，TGF-β，FGF，PDGF，and insulin-like growth factor（IGF）.TGF-β could promote the synthesis and deposition of collagen fibers，accelerate wound healing，change the tension of local tissue and affect the formation of scarring（Figure 2-6）.
FGF could induce the production of capillaries and accelerate the growth of epithelium and granulation tissue.PDGF is the peptide secreted by platelet α particle，which could promote the cells from interphase into mitotic phrase，and promote cell proliferation and differentiation.PDGF is synthesized and secreted by endothelial cells，smooth muscle cells，fibroblast cells and macrophages，which enables inflammatory cells infiltrating into the wound site and promotes the formation of granulation tissue when skin tissue is damaged.Currently，the growth factor agents approved by China Food and Drug Administration include recombinant bovine basic fibroblast growth factor for external use gel，recombinant human basic fibroblast growth factor and recombinant human epidermal growth factor external solution.
2.Matrix metalloproteinases affecting wound healing process
Matrix metalloproteinases（MMPs）are intrapeptidase assisted by Ca2+and Zn2+，whose activity is inhibited by tissue inhibitor of metalloproteinases（TIMPs）.MMPs are involved in the degradation of extracellular matrix such as collagen.Studies have shown that the expression of MMPs is very low in intact skin tissue and is up-regulated after skin injury.In addition，TIMPs can delay wound healing，suggesting that MMPs are key molecules in wound healing.Fibroblasts secrete MMPs to promote cell migration and degrade unstable extracellular matrix.Moreover，MMPs can promote macrophages infiltration in the wound to remove necrotic tissue，promote establishing microcirculation in the wound area，and accelerate granulation tissue formation.
3.Inflammation-related mircoRNA affecting wound healing process
Inflammation response in wound area plays a key role in wound healing.The disruption of inflammation response can delay wound healing，lead infection，and generate hyperplastic scar and keloid.MircoRNA（miRNA），21-23 nucleotide noncoding single-stranded RNA，is derived from eukaryotes.miRNA is bond with mRNA and inhibit the gene expression of transcription level.Inflammation-related miRNA is the key regulator of the inflammatory response and tissue repair.Multiple kinds of miRNA related to wound healing have been identified，and the dysfunction of miRNA could lead pathological wound healing，such as slow healing process and scarring.(https://www.daowen.com)
4.Oxygen affecting wound healing process
Clinical studies found that more bleeding wounds heal well while less bleeding wounds suffer poor healing.Any kind of wound healing requires sufficient blood perfusion and oxygen supply.A clinical study have demonstrated that oxygen therapy prior to surgery could reduce 50％of postoperative wound infections in patients with colorectal resection.Hyperbaric oxygen therapy also achieves satisfactory results in chronic delayed healing wound.Thus，oxygen therapy plays very important roles in wound healing and preventing infection.
5.Wet wound environment affecting wound healing process
White et al.observed that wound healed faster in humid environment than in dry conditions through the pig experimental models，and proposed the theory of wet wound healing.Subsequently，a number of studies have confirmed this theory.The wet environment of the wound can make the wound base moist，stimulate the formation of vessels and granulation tissue，shorten the healing period and reduce the possibility of scar formation.
The theory of wet wound healing suggests that wet dressings could keep wound moist and accelerate wound healing.The wet dressings could keep wound moist，promote fibroblasts proliferation and capillary formation，and release and activate the collagen enzyme，especially protease and urokinase dissolving necrotic tissue.The improvement of wound microenvironment can attract a large number of inflammatory cells to secrete a variety of growth factors，promoting wound healing.In addition，wet dressings could reduce the adhesion between dressings and wound，and reduce patients' pain during dressings change and secondary injury.At present，the theory of wet wound healing is still controversial in China.Some scholars believed that the closed moist environment would cause the proliferation of pathogenic bacteria in the wound area and lead wound infection.