2.2.2.2　Chronic refractory wound

Chronic refractory wound（ulcer）includes traumatic ulcer，variceal ulcer of lower extremities，pressure ulcer and diabetic ulcer.It has long duration period，affects esthetics，and is accompanied with serious complications，which affect the patients'quality of life significantly.The incidence，lesion location，age and susceptible population of chronic refractory skin is different between developed and developing countries.In China，chronic refractory wound caused by trauma is given priority to adolescents and young adults，and diabetic，oppressive，venous ulcers are prominent in the elderly over the age of 60.

The etiology and pathogenesis of chronic refractory wound has not yet been fully elucidated.The pathogenesis differs among different kinds of chronic refractory wounds（Figure 2-7）.Studies have shown that the down expression of extracellular protein fiber connection gene lead to the damage of tissue repair cell scaffold and delay wound healing.The excessive apoptosis of the fibroblast reduce the generation of dermal collagen fibers and delay wound healing.The concentration change of growth factors in wound site and dysfunction of regulation network delay wound healing.Ca2+signaling pathways，mitogenactivated protein kinases（MAPKs），Jaks-STATs，and protein kinase C（PKC）are shown to mediate the healing process of chronic refractory wound.The relevant studies need to be further verified.

Due to the differences in etiology and pathogenesis，the therapies are differed among different kinds of chronic refractory wounds.At first，performing surgical treatment（debridement）for skin ulcers；second，adopting some measures to promote traumatic ulcer healing.Blood sugar and varicose problems need to be first treated in the treatment for diabetic ulcer and variceal ulcer of lower extremities，respectively.(https://www.daowen.com)

Recently，treatment for chronic refractory wound include new types of dressing materials，growth factor agent as well as stem cells and tissue engineering.Hydrogel，hydrophilic three-dimensional network，can absorb a large amount of water or liquid，and has good elasticity，swelling and surface properties，and biological safety，which is a good material for wound dressings and tissue engineering.Growth factors are involved in the whole stages of wound healing.Adding exogenous growth factors could promote proliferation and differentiation of cells and regulate signal transduction.Commercially growth factor agents approved by Food and Drug Administration（FDA）of the United States include human recombinant platelet derived growth factor（PDGF），recombinant human/bovine fibroblast growth factor and epidermal growth factor（EGF），etc.Transgenic method of wound healing transfers the naked DNA of growth factors gene into local wound sites through injection and gene gun，promoting cell proliferation，angiogenesis and wound healing.