EGF increases short-term type I collagen accumulation during wound healing in diabetic rats

Abstract

Continuous topical application of epidermal growth factor (EGF) to granulation tissue increases the rate of collagen accumulation. It is believed that the clinical use of growth factors, such as EGF, may become common in the treatment of impaired wound healing in the near future. Impairments in the production and degradation of wound collagens have been demonstrated in diabetes mellitus. We studied the effects of a single, local application of EGF on collagen content, collagenase activity, and the ratio of type III and type I collagens within granulation tissue using polytetrafluoroethylene (PTFE) wound cylinders in 48 streptozotocin-induced diabetic rats in order to determine potential benefits of EGF to wound healing in diabetics. Wound collagen content in EGF-treated diabetic animals was significantly higher than in diabetic controls during the first 10 days of wound healing (236% on day 5, P < .001; 140% on day 10, P < .01), but decreased to significantly lower levels by day 15 of healing (71% of diabetic controls, P < .01; 47% of nondiabetic controls, P < .01). An 18% increase in diabetic wound protease activity was observed following application of EGF ( P < .001). The ratio of type III collagen to total wound collagen within the granulation tissue was significantly reduced ( P < .001) following EGF application. We demonstrate that a single, topical application of EGF promotes early synthesis of type I collagen, thereby deranging the usual type III/total collagen ratio, and is associated with increased wound protease activity.