Experimental studies in animals have demonstrated that the topical application of epidermal growth factor accelerates the rate of epidermal regeneration of partial-thickness wounds and second-degree burns. We conducted a prospective, randomized, double-blind clinical trial using skin-graft-donor sites to determine whether epidermal growth factor would accelerate the rate of epidermal regeneration in humans. Paired donor sites were created in 12 patients who required skin grafting for either burns or reconstructive surgery. One donor site from each patient was treated topically with silver sulfadiazine cream, and one was treated with silver sulfadiazine cream containing epidermal growth factor (10 micrograms per milliliter). The donor sites were photographed daily, and healing was measured with the use of planimetric analysis. The donor sites treated with silver sulfadiazine containing epidermal growth factor had an accelerated rate of epidermal regeneration in all 12 patients as compared with that in the paired donor sites treated with silver sulfadiazine alone. Treatment with epidermal growth factor significantly decreased the average length of time to 25 percent and 50 percent healing by approximately one day and that to 75 percent and 100 percent healing by approximately 1.5 days (P less than 0.02). Histologic evaluation of punch-biopsy specimens taken from the centers of donor sites three days after the onset of healing supported these results. We conclude that epidermal growth factor accelerates the rate of healing of partial-thickness skin wounds. Further studies are required to determine the clinical importance of this finding.

The ability of surgeons to accelerate wound healing through pharmacologic intervention is limited. The effects of locally applied, biosynthetic human epidermal growth factor (EGF) and transforming growth factor-beta (TGF-beta) on tensile strength of experimental incisions were investigated. A single dose of EGF in saline failed to increase tensile strength over controls. Thus, EGF was incorporated into multilamellar liposomes, which prolonged the exposure of incisions to EGF (p less than 0.001). A single dose of EGF in multilamellar liposomes produced a 200% increase in wound tensile strength over controls between 7 and 14 days (p less than 0.05). Light and electron microscopy of the wounds revealed increased collagen formation and fibroblast proliferation. A single dose of TGB-beta in a collagen vehicle stimulated a 51% increase in wound tensile strength at 9 days (p less than 0.01). We conclude that addition of EGF and TGF-beta in appropriate vehicles stimulates early transient increases in wound tensile strength in normal rats.

Normal regeneration of the epidermis after a split-thickness injury requires mitosis and migration of epidermal cells from the residual epidermal appendages within the wound as well as from the intact epithelium surrounding the injury (1). Acceleration of epidermal regeneration by a pharmacologic agent may result in more rapid would healing. Epidermal growth factor (EGF), a well-described (2) small peptide hormone, is a potent mitogen for human epidermal cells in vitro (3). A limited number of clinical and experimental attempts to show enhanced epidermal regeneration of split-thickness injuries using mouse EGF have been unsuccessful (4-6). The purpose of this study was to evaluate the in vivo effectiveness of biosynthetic human EGF obtained from genetically engineered yeast in accelerating epidermal regeneration in split-thickness wounds and partial-thickness burns in an experimental animal model. Materials and MethodsReagents. Human EGF (hEGF) was produced as described (7). Lanolin was from Squibb Pharmaceutical Co. (Princeton, N J) and 1% silver sulfadiazine in a water-miscible base (Silvadene) was from Marion Laboratories (Kansas City, MO).Split-thickness Epidermal Wounds. 84 split-thickness wounds (0.005 inches thick, 1 × 1 cm) were made on the dorsal thorax of four adult miniature pigs (Vim-Vet Laboratories, Marion, ID). Twice a day, 28 wounds on each pig were treated with hEGF in cream (lanolin or Silvadene), 28 were treated with the cream alone, and 28 were untreated. Four wounds from each group on each pig were randomly selected daily and entirely excised at a depth of 0.007 inches, including 5 mm of surrounding normal skin. Epidermis and dermis were readily separated from excised specimens after incubation in trypsin, and wounds were considered healed when no defect was present (8).Partial-thickness Burns. A brass template (3 × 5 cm, 430 g) was heated to 70°C in a constant-temperature water bath and then pressed for 10 s in contact with depiliated dorsal skin of Yorkshire piglets (14-20 pounds); the resultant blister was removed. Histological evaluation of biopsy specimens confirmed that partial-thickness burns were produced. On each pig, two burns were treated twice a day with hEGF in Silvadene (0.5 ml cream per square centimeter of burn), two burns were treated with Silvadene alone, and two were untreated.

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