BackgroundTongue is complex muscular organ that may be affected by recurrent or chronic ulcerations and malignances that require effective treatment to enhance healing and tissue regeneration. So, this study aimed to evaluate the efficiency of erythropoietin (EPO) hydrogel as an anti-inflammatory and an inducer of neovascularization during healing of induced rats’ tongue defects.MethodsThirty six rats were divided into three groups; Group I (negative control): tongues were left without ulceration and received no treatment, Group II (positive control): tongue defects were prepared on the tongues’ dorsal surfaces, measuring (5 mm × 2 mm) using a tissue punch rotary drill for standardization, and left untreated, Group III (EPO group): tongue defects were prepared as in group II, then injected circumferentially around wound margins with a single high dose of EPO hydrogel of 5000 U/kg on the day of defect preparation. Animals were euthanized on seventh and fourteenth days after treatment, tongue specimens were collected, and paraffin blocks were prepared and processed for histological assessment by hematoxylin and eosin stain and immunohistochemical evaluation of anti-iNOS and anti-VEGF followed by histomorphometrical analysis and the relevant statistical tests.ResultsAt both time points, the EPO treated group showed significantly enhanced tissue regeneration marked by the histologically better regenerated tissue with well developed, thick walled and well-organized blood vessels and significant reduction in defect depth compared to positive control group. EPO group also showed significant decrease in iNOS and significant increase in VEGF antibodies indicating its anti-inflammatory and neovascularization effects respectively.ConclusionEPO treatment can significantly accelerate regeneration and filling of tongue defects by reducing tissue inflammation and enhancing neovascularization. Therefore, EPO could be a potential therapeutic strategy for accelerating healing of tongue ulcers. However, further investigations are required to optimize the dose and unravel any potential side effects before its clinical application.