Background Healing and regeneration of large bone defects are a challenging problem for reconstructive orthopedic surgeons. Purpose This study investigated the effectiveness of chitosan scaffold (CS), platelet gel (PG) and their combination (CS-PG) on healing process of an experimentally induced critical sized segmental bone defect model in rat. Methods Fifty bilateral defects were created in the mid diaphysis of the radial bones of 25 Sprague-Dawley rats. The animals were randomly divided into five equal groups. The bone defects were either left untreated or treated with corticomedullary autograft, CS, PG or CS-PG. Plain radiographs were provided from the radial bones on weeks 2, 5, and 8 after injury. In addition, clinical examinations were done for the healing radial bones. The animals were euthanized after 8 weeks of injury, and their harvested samples were evaluated by gross morphology, histopathology, scanning electron microscopy, CT-scan, and biomechanical testing. Results Compared with the defect group, the PG and autograft treated bone defects had significantly superior radiological scored values, bone volume and biomechanical performance which had positive correlation with their superior gross pathological, histopathological and ultra-structural features. Compared with the untreated defects, the PG and CS-PG treated defects showed significantly superior structural and functional properties so that PG had the highest value. In addition, CS had low value in bone regeneration. Although combination of CS and PG improved the healing efficacy of the CS, this strategy reduced the ability of PG to increase osteoconduction and osteoinduction during bone regeneration. Conclusion Application of PG alone enhanced bone healing and can be regarded as a promising option for bone tissue engineering in clinical settings. Chitosan was not effective in bone reconstruction surgery and further investigations should be conducted to find a suitable carrier for PG.

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