Background: Induced pluripotent stem cells (iPSCs) can generate bone marrow mesenchymal stem cells (BMSCs) as seed cells for tissue-engineered bone to repair bone defects. In this study, we investigated the effects of hydroxyapatite-zirconia (HA/ZrO 2 ) composites combined with iPSC-derived BMSCs as a bone substitute on repairing skull defects in rats.Methods: Human urinary cells isolated from a healthy donor were reprogramed into iPSCs and then induced into BMSCs. Immunocytochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) were used to examine the characteristics of the induced MSCs. The iPSC-derived BMSCs were cultured on HA/ZrO 2 composites, and cytocompatibility of the composite was analyzed by cell counting kit-8 (CCK-8) assays, RT-PCR, and scanning electron microscopy. Then, HA/ZrO 2 combined with iPSCderived expanded potential stem cells (EpSCs) were transplanted onto skull defects of rats. The effects of this composite on bone repair were evaluated by IHC. Results:The results showed that MSCs induced from iPSCs displayed the phenotypes and property of normal BMSCs. After seeding on the HA/ZrO 2 , iPSC-derived BMSCs had the ability to proliferate and differentiate into osteoblasts. After transplantation, iPSC-derived BMSCs on HA/ZrO 2 promoted construction of bone on rat skulls.Conclusions: These results indicated that transplantation of a HA/ZrO 2 combined with iPS-derived BMSCs is feasible to reconstruct bones and may be a substantial reference for iPSC-based therapy for bone defects.