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he aim of the present study was to investigate the effects from local co-administration of erythropoietin and cancellous bone granules (bone substitute) on haematological parameters and bone regeneration in a calvarial bone defect model in rats. The study was performed with 12 male Wistar albino rats, 6 months of age. Two symmetrical 5-mm critical-size defects were created in the calvaria of each animal. A combination of bone substitute and physiological saline-soaked collagen membrane was placed in the right defect site, whereas bone substitute + erythropoietin-soaked collagen membrane – in the left defect site. Bone regeneration was monitored by radiography and computed tomography on the 30th and 90th days after the surgery. Blood samples were collected at the same time intervals for determination of erythrocyte counts, haemoglobin content and haematocrit. The independent application of a cancellous bone granules xenograft resulted in bone regeneration of critical-size calvarial bone defects in rats. Its co-administration with erythropoietin enhanced the bone healing process.