Effects of Erythropoietin-Treatment on Wound Healing in Burn Patients. Investigated Using Immunohistochemical and Histological Methods, Analyzed Using AI. Post Hoc Analysis of the Randomized, Placebo-Controlled Clinical Trial “EPO in Burns”

Background: Scars often negatively impact individuals' self-esteem, making them self-conscious and lowering their self-confidence.To help patients avoid scar formation after burns or accidents, researchers are trying to better understand the biological mechanisms leading to scar formation and develop effective clinical treatments. Burns are leading causes of mortality and morbidity, including prolonged hospitalization, disfigurement, and disability. Erythropoietin (EPO) is a well-known hormone causing erythropoiesis. However, EPO may play a role in healing acute and chronic wounds due to its anti-inflammatory and pro-regenerative effects. Losing the protective barrier of their skin puts burn patients at high risk. Typical manifestations of a severe burn injury are immunosuppression, hyper-metabolism, and complications such as wound infection and sepsis, with subsequent multi-organ failure and death. Therefore, burns lead to the risk of delayed and poor recovery. For this reason, early wound closure is essential for the prognosis and rehabilitation of burn patients.The large, prospective, placebo-controlled, randomized, double-blind, multi-center clinical trial "EPO in Burns" was initiated to investigate the effects of EPO versus placebo treatment in severely burned patients. The primary endpoint of "EPO in Burns" was defined as the time elapsed until complete re-epithelialization of a designated split skin graft donor site. Methods: Previous pre-clinical studies have shown that low-dose Erythropoietin (EPO) has regenerative and cytoprotective effects, for example, in animal models and cell cultures. However, the molecular mechanisms by which EPO influences scar formation or wound healing in human skin tissue are still unclear. This study evaluates the effect of EPO on skin graft donor site wound healing in human patients using immuno-histochemical methods. The verum (n 45) and control (n 39) groups were compared with regard to the time it took for study wounds (a predefined split skin graft donor site) to reach the three stages of wound healing (re-epithelialization levels). The effect of systemic application of EPO on immunohistochemical indicators of wound healing is tested using skin samples from a clinical trial that compared EPO-treated to placebo-treated groups. Results: The immuno-histochemical analyses failed to uncover any strong patterns differentiating treatment and control groups, except Von Willebrand Factor (VWF), which showed signs of decreased expression in the EPO-treated group. Conclusion: To test whether EPO is one of the key pro-regenerative agents in skin regeneration, as suggested in previous studies [1], a clinical trial was conducted to assess how wound healing is affected by systemic treatment with EPO. IHC analyses failed to uncover any strong effects differentiating treatment and control groups, except VWF, which showed decreased expression in the EPO treatment group. More research is needed to determine if different dosages, application schemes, or topical applications of EPO may improve wound healing at the donor site of skin grafts and if the effect of EPO on wound healing is dose-dependent.