Acceleration of partial-thickness burn wound healing with topical application of heparin-binding EGF-like growth factor (HB-EGF)

Heparin-binding EGF-like growth factor has been identified in human bum- wound fluid and in the epithelial cells of excised human partial-thickness burns. In the present study, the effect of heparin-binding EGF-like growth factor on burn-wound healing was evaluated by incorporating purified, recombinant heparin-binding EGF-like growth factor into slow-release cholesterol-lecithin pellets that were applied topically to partial-thickness burns in mice. Both experimental (heparin-binding EGF-like growth factor- treated) and control (untreated) mice were sacrificed on days 3, 5, and 10 after burn. Total burn-wound area, histology, keratinocyte proliferation, and in situ hybridization analysis for transforming growth factor-α were determined for each wound. The mean wound area of the experimental group on day 5 after burn was 1.07 cm², compared with 2.20 cm² for controls (p = 0.04). Cellular proliferation (as measured by immunohistochemical detection of 5-Bromo-2-deoxyuridine) on day 5 after burn in marginal keratinocytes and follicular epithelial cells was greater in the experimental group than in the control group. In situ hybridization showed up-regulation of transforming growth factor-α mRNA levels in experimental animals by day 5 after burn. Topical application of heparin-binding EGF-like growth factor significantly accelerates the reepithelialization of murine partial-thickness burns, increases keratinocyte proliferative activity, and enhances production of endogenous transforming growth factor-α mRNA.