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Background:The treatment for long bone defects has been a hot topic in the field of regenerative medicine.This study aimed to evaluate the therapeutic effects of calcium sulfate (CS) combined with platelet-rich plasma (PRP) on long bone defect restoration.Methods:A radial bone defect model was constructed through an osteotomy using New Zealand rabbits.The rabbits were randomly divided into four groups (n =10 in each group):a CS combined with PRP (CS-PRP) group,a CS group,a PRP group,and a positive (recombinant human bone morphogenetic protein-2) control group.PRP was prepared from autologous blood using a two-step centrifugation process.CS-PRP was obtained by mixing hemihydrate CS with PRP.Radiographs and histologic micrographs were generated.The percentage of bone regenerated bone area in each rabbit was calculated at 10 weeks.One-way analysis of variance was performed in this study.Results:The radiographs and histologic micrographs showed bone restoration in the CS-PRP and positive control groups,while nonunion was observed in the CS and PRP groups.The percentages of bone regenerated bone area in the CS-PRP (84.60 ± 2.87％) and positive control (52.21 ± 4.53％) groups were significantly greater than those in the CS group (12.34 ± 2.17％) and PRP group (16.52 ± 4.22％) (P ＜ 0.001).In addition,the bone strength of CS-PRP group (43.l 0 ± 4.10％) was significantly greater than that of the CS group (20.10 ± 3.70％) or PRP group (25.10 ± 2.10％) (P ＜ 0.001).Conclusion:CS-PRP functions as an effective treatment for long bone defects through stimulating bone regeneration and enhancing new bone strength.