Topical exposure of nitric oxide gas to wounds such as chronic non-healing wounds may be beneficial in promoting healing and preparing the wound bed for further treatment and recovery. Nitric oxide gas may be used to reduce the microbial infection, manage exudates secretion by reducing inflammation, upregulate expression of endogenous collagenase to locally debride the wound, and regulate the formation of collagen. High concentration of nitric oxide ranging from 160 400 ppm may be used without inducing toxicity in the healthy cells around a wound site. Exposure to the high concentration for a first treatment period reduces the microbial burden and inflammation, and increases collagenase expression to debride necrotic tissue at the wound site. After a first treatment period, a second treatment period at a lower concentration of nitric oxide, preferably ranging from 5 20 ppm may be used to restore the balance of nitric oxide and induce collagen expression aiding in the wound closure.

 
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