The combined effect of recombinant human epidermal growth factor and erythropoietin on full-thickness wound healing in diabetic rat model

Diabetic wound is a chronic wound in which normal process of wound healing is interrupted. Lack of blood supply, infection and lack of functional growth factors are assumed as some of the conditions that lead to non-healing environment. Epidermal growth factor (EGF) acts primarily to stimulate epithelial cell growth across wound. Erythropoietin (EPO) is a haematopoietic factor, which stimulates the production, differentiation and maturation of erythroid precursor cells. This study hypothesised combining these two factors, non-healing process of diabetic wound will be compensated and eventually lead to acceleration of wound healing compared with single growth factor treatment. A total of 30 diabetic Sprague-Dawley rats were divided into three treatment groups (single treatment of rh-EPO or rh-EGF or combined treatment on a full-thickness skin wound). To assess the wound healing effects of the components, the wound size and the healing time were measured in each treatment groups. The skin histology was examined by light microscopy and immunohistochemical analysis of proliferating markers was performed. The combined treatment with rh-EPO and rh-EGF improved full-thickness wound significantly (P < 0 05) accelerating 50% healing time with higher expression of Ki-67 compared with single growth factor-treated groups. The combined treatment failed to accelerate the total healing time when compared with single growth factor treatments. However, the significant improvement were found in wound size reduction in the combined treatment group on day 4 against single growth factor-treated groups (P < 0 05). This study demonstrated that the combined treatment of rh-EPO and rh-EGF improved the wound healing possibly through a synergistic action of each growth factor. This application provides further insight into combined growth factor therapy on non-healing diabetic wounds.