Epoetin Alpha and Epoetin Zeta: A Comparative Study on Stimulation of Angiogenesis and Wound Repair in an Experimental Model of Burn Injury

Abstract

Deep second-degree burns are characterized by delayed formation of granulation tissue and impaired angiogenesis. Erythropoietin (EPO) is able to stimulate angiogenesis and mitosis, activating vascularization and cell cycle. The aim of our study was to investigate whether two biosimilar recombinant human erythropoietins, EPO-αand EPO-Z, may promote these processes in an experimental model of burn injury. A total of 84 mice were used and a scald burn was produced on the back after shaving, in 80°C water for 10 seconds. Mice were then randomized to receive EPO-α(400 units/kg/day/sc) or EPO-Z (400 units/kg/day/sc) or their vehicle (100 μL/day/sc 0.9% NaCl solution). After 12 days, both EPO-αand EPO-Z increased VEGF protein expression. EPO-αcaused an increased cyclin D1/CDK6 and cyclin E/CDK2 expression compared with vehicle and EPO-Z (p<0.001). Our study showed that EPO-αand EPO-Z accelerated wound closure and angiogenesis; however EPO-αresulted more effectively in achieving complete skin regeneration. Our data suggest that EPO-αand EPO-Z are not biosimilars for the wound healing effects. The higher efficacy of EPO-αmight be likely due to its different conformational structure leading to a more efficient cell proliferation and skin remodelling.