EFFECT OF EPIDERMAL GROWTH FACTOR ON WOUND HEALING

Abstract

Activities aimed at treating and/or monitoring the healing of wounds consume many nursing hours. However, most of the treatments used by nurses in caring for wounds are best classified as "reports of techniques" and are not based on research. Though no single initiator or promoter of wound healing has been isolated, epidermal growth factor (EGF), a naturally occurring polypeptide, has been reported to promote epidermal growth in vitro. In vivo, the application of EGF has been reported to increase proliferation and differentiation of epidermal tissue in newborn mice and to enhance the healing of corneal wounds in rabbits. Originally found in the submaxillary gland of male mice, EGF has now been found in the urine of humans. No reports have documented the in vivo effects of application of EGF to epidermal wounds of animals to determine if it will promote wound healing. The purposes of this study were to further elucidate the physiological and perhaps therapeutic function of EGF and to evaluate the feasibility in terms of availability, cost, and manageability of the pig as an animal model for controlled investigation of clinical nursing problems. Wound healing is a composite phenomenon of distinct yet interrelated phases: epithelialization, contraction, and fibrous healing. The reepithelialization of the wound is the result of migration of epidermal cells adjacent to the wound edge and differentiation of the new cells. Because of the risks and ethics involved in repeated biopsy of human wounds and the prematurity of use of EGF in humans, the specific problem this study was designed to answer is: Does the topical application of mouse epidermal growth factor (mEGF) increase the rate of healing of epidermal wounds in the domestic pig? An experimental design was used to test four hypotheses. Three of the hypotheses related to the process of wound healing were: (1) Topical application of 40 ng of mEGF will increase migration of keratinocytes over the wound. (2) Topical application of 40 ng of mEGF will increase the mitotic index. (3) Topical application of 40 ng of mEGF will increase the differentiation of keratinocytes over the wound. A fourth hypothesis, topical application of 40 ng of mEGF will increase the protein/DNA ratio in keratinocytes adjacent to and covering the wound, was tested since EGF is reported to be a potent mitogen increasing DNA synthesis and increasing intracellular protein. Using a modification of the Winter method, 82 wounds were created on the backs of ten young Yorkshire mix pigs in order to simulate the healing of two wounds over time. Mouse EGF was applied every two hours for six hours then every six hours for 48 hours (total of 54 hours) and 0.9 percent sodium chloride was applied to the control wounds in identical fashion. Tissue obtained from randomly assigned timed biopsises were examined histologically for the migration, mitosis, and differentiation of the keratinocytes. In addition, a portion of each biopsy was utilized for determination of protein/DNA ratio. Dependent t-tests of means showed no statistically significant differences between mEGF treated experimental and control wounds. Therefore, none of the hypotheses were supported. Graphic presentation of the data does indicate differences at specific points especially in the first 18-48 hours post-wounding. The pig was found to be a satisfactory model for controlled studies since the epidermal tissue is similar and the animals are relatively inexpensive, readily available, and become domesticated or relatively easy to handle in a short period of time.