Dense biomaterial plays an important role in bone replacement. However, it fails to induce bonecell migration into graft material. In the present study, a novel bone graft substitute (BGS)consisting of porous gradient hydroxyapatite/zirconia composite (PGHC) and gelatin/chitosanslow‐releasehydrogelcontainingbonemorphogeneticprotein2andbonemesenchymalstemcellswasdesignedandpreparedtorepairlumbarvertebraldefects.Themorphologicalcharacteristicsofthe BGS evaluated by a scanning electron microscope showedthat it had a three‐dimensional net-workstructurewithuniformlydistributedchitosanmicrospheresonthesurfacesofthegraftmate-rial and the interior of the pores. Then, BGS (Group A), PGHC (Group B), or autologous bone(Group C) was implanted into lumbar vertebral body defects in a total of 24 healthy rhesusmonkeys. After 8 and 16 weeks, anteroposterior and lateral radiographs of the lumbar spine,microcomputed tomography, histomorphometry, biomechanical testing, and biochemical testingfor bone matrix markers, including Type I collagen, osteocalcin, osteopontin, basic fibroblastgrowth factor, alkaline phosphatase, and vascular endothelial growth factor, were performed toexaminethereparativeefficacyoftheBGSandPGHC.TheBGSdisplayedexcellentabilitytorepairthe lumbar vertebral defect in rhesus monkeys. Radiography, microcomputed tomography scan-ning, and histomorphological characterization showed that the newly formed bone volume in theinterior of the pores in the BGS was significantly higher than in the PGHC. The results of biome-chanical testing indicated that the vertebral body compression strength of the PGHC implantwas lower than the other implants. Reverse‐transcription polymerase chain reaction and westernblot analyses showed that the expression of bone‐related proteins in the BGS implant was signif-icantlyhigherthaninthePGHCimplant.TheBGSdisplayedreparativeeffectssimilartoautologousbone. Therefore, BGS use in vertebral bone defect repair appears promising.