The effect of Human Recombinant Epidermal Growth Factor on neovascularization and pedicle division time in a rat interpolation flap model

Aim:In Plastic Surgery practice, interpolation flaps are among the more frequently preferred flaps for closure of large and deep defects. However, waiting for at least 2 to 3 weeks for pedicle division is still a serious problem in clinical practice, since prolonged hospitalization of patients causes various morbidities and increases medical costs accordingly. Epidermal Growth Factor (EGF) is an agent used in clinical practice to enhance wound healing. The division time for the pedicle of interpolation flaps is depended on the neovascularization from the recipient bed, and this process includes wound healing stages. In this study, we aimed to investigate the effect of EGF on the flap in early pedicle division. Materials and Methods: In the study, 36 female and male rats of Wistar albino genus weighing between 200±50 grams were used. Regardless of their weight and gender, the rats were divided into 2 main groups as control and study groups. Each main group was divided into 3 subgroups in itself. A random cranial based skin flap of the size of 5x5cm was elevated from the back region of all subjects, including all layers of the skin and panniculus carnosus. While the 2.5 cm portion of the defect was closed primarily,the flap was inset into the distal 5x2.5 cm portion. Before the inset of the flap, in the study group, a single dose of 20 micrograms Epidermal Growth Factor was injected to the recipient site and to the wound edges, divided into ¾ and ¼ respectively. The subjects in the control group were not injected with any other substance. On the 8th, 11th and 14th postoperative days, proximal pedicle division was performed on the 6 rats in each subgroup. Each flap was followed for the next seven days following the division from its pedicle. After the seventh day, each flap was photographed, and histopathological samples were collected. The photographs were transferred to the Adobe Acrobat Reader DC 2021 program and the living areas and necrosis areas in each flap were compared by counting pixels and calculating percentages. The flaps of all subjects were examined histopathologically and compared on parameters of reepithelialization, inflammation, fibroblastic activity, granulation tissue formation and neovascularization. Results:When the statistical results were evaluated by comparing living flap area and necrosis area, a significant difference was observed between the subgroups in the control group (p=0.009), but there was no significant difference between the subgroups in the study group (p=0.115). When the histopathological results were evaluated statistically, it was observed that fibroblastic activity, the amount of granulation tissue and neovascularization were significantly higher in the study group whose pedicle was divided on the 8th postoperative day compared to the control group whose pedicle was divided on the same day (p<0.05). Also, the amount of granulation tissue was significantly higher in the study group whose pedicle was divided on the 11th postoperative day compared to its control (p=0.023). Besides, the level of neovascularization was significantly higher in the study group whose pedicle was divided on the 14th postoperative day compared to the control group whose pedicle was divided on the same day (p=0.027). Conclusion:As a result of our study,significant difference was measured in terms of living flap area on the 11th day after the administration of Epidermal Growth Factor in interpolation flaps, while in all groups that underwent pedicle division on different days, the histopathological evaluations yielded significant results in different parameters, especially neovascularization. The study showed that the use of Epidermal Growth Factor accelerates wound healing and has a positive effect on neovascularization. It was concluded that interpolation flaps can be divided earlier with Epidermal Growth Factor treatment. Key Words:interpolation flap, pedicle division, recombinant human epidermal growth factor