Continuous EGF application impairs long-term collagen accumulation during wound healing in rats

Abstract

Continuous topical application of epidermal growth factor (EGF) to granulation tissue has been demonstrated to increase the rate of collagen accumulation in wounds. Studies from this laboratory have indicated that a single topical application of EGF leads to a short period of elevated wound collagen content, followed by a rapid breakdown of this newly acquired collagen. In light of recent clinical trials of EGF as an aid to wound healing, we studied the long-term effects of continuous EGF injection. Standard polytetrafluoro-ethylene (PTFE) wound cylinders were surgically placed in the dorsal midline of 40 male Sprague-Dawley rats. Rats received EGF daily for 14 days, at which time all injections ceased. Wound cylinders were removed for analysis from five test animals and five controls on study days 14, 21, 28, and 35. Wound collagen content in EGF-treated animals was significantly higher than in controls on the 14th day of the study (330% higher, P < .002), but dropped to lower levels on each succeeding day (day 21: 97% of control, NS; day 28: 63% of control, NS; day 35: 72% of control, P < .03). There was a significant increase in wound collagenase activity only on days 14 and 21, but not on days 28 and 35. We demonstrated that continuous application of EGF may artificially elevate wound collagen content, thereby leading to increased wound catabolism on cessation of treatment.