EPIDERMAL GROWTH-FACTOR ACCELERATES CONNECTIVE-TISSUE WOUND-HEALING IN THE PERFORATED RAT MESENTERY

Epidermal growth factor (EGF) has been reported to stimulate healing of wounds in skin, cornea, and gastric mucosa. In the present study, we further investigate the effect of endogenous and exogenous EGF in healing of connective tissue wounds using the rat perforated mesentery model. Healing of mesenteric perforations is accomplished by the connective tissue fibroblasts since there are no interfering variables such as interactions of epithelial cells, desiccation, or foreign materials such as sutures or subcutaneous implants. We performed laparotomy in 114 adult male Sprague-Dawley rats and made 20 standardized perforations in the mesentery of each rat with a scalpel. Rats were randomly assigned to five groups. Group I received no treatment after surgery; Group II received intraperitoneal injections of phosphate-buffered saline (PBS) after surgery and then twice daily for the following 3 days; Group III received 10 μg of EGF in the PBS injections according to the same regimen as Group II; Group IV had sham exploration of the submandibular salivary glands; and Group V animals had excision of the submandibular glands 3 days before laparotomy to deprive the main source of EGF in rat. On Days 4 through 10 after surgery rats were sacrificed and the percentage of perforations in each rat which were closed was determined. The curves for the time course of wound closure for Groups IV and V were not different indicating that endogenous submandibular EGF does not play a role in healing of mesenteric wounds. The curves for the time course of wound closure for Groups I, II, and III all had the same shape, but the curve for Group III rats treated with EGF was shifted to earlier postoperative times with significantly higher percentages of wound closure during postoperative Days 5 and 8 compared to controls that received injections of PBS vehicle or no treatment. These results indicate that endogenous submandibular EGF did not affect healing of mesenteric perforations, whereas intraperitoneal injections of EGF during the early postoperative period stimulated earlier closure of mesenteric perforations possibly by more rapidly initiating early phases of connective tissue healing. The results also suggest that local access of EGF to the wound is important. © 1992.