Abstract: Objective To observe the effect of a new biomaterial in promoting the bone regeneration for repairing critical-size cranial defects in SD rats. Methods Critical-size cranial defects were induced in 3-month-old male Sprague-Dawley rats and repaired with the implants of calcium phosphate from growth factor enhanced matrix 21 (CaPfromGEM21, control), CaPfromGEM21 preloaded with 10 ng bone morphogenetic protein-2 (BMP-2), CaPfromGEM21 preloaded with 100 ng BMP-2, CaPfromGEM21 preloaded with 0.3 μg platelet-derived growth factor-BB (PDGF-BB), or CaPfromGEM21 preloaded with 3 μg PDGF-BB. The defects were examined 6 weeks after the surgery with X-ray, micro-CT, HE staining and quantitative assessments. Results X-ray showed defect repair in all the groups. The fracture line became obscure, and the defects were almost fully repaired by the regenerated bone tissues in PDGF-BB group. Micro-CT demonstarted new bone formation in the defects. The new bone volume was significantly greater in PDGF-BB groups than in BMP-2 groups (P<0.05). HE staining revealed the presence of new bones in the defects and new vessels in and around the new bones without inflammatory cells. The new bone area fraction was significantly greater in 10 ng BMP-2 group and 0.3 μg PDGF-BB group than in the control group (P<0.05), and the new vessel density was similar in the all the 4 cytokine-preloaded groups and all significantly greater than that in the blank and CaPfromGEM21 control group (P<0.05). Conclusion CaPfromGem21 combined with BMP-2 or PDGF-BB has good biocompatibility and can better promote bone regeneration for repairing bone defects.