Induced pluripotent stem cells(iPSCs)have great potential due to their proliferation and differentiation capability.The objectives of this study were to generate iPSC-derived mesenchymal stem cells(iPSC-MSCs),and investigate iPSC-MSC proliferation and osteogenic differentiation on calcium phosphate cement(CPC)containing biofunctional agents for the first time.Human iPSCs were derived from marrow CD34+cells which were reprogrammed by a single episomal vector.iPSCs were cultured to form embryoid bodies(EBs),and MSCs migrated out of EBs.Five biofunctional agents were incorporated into CPC:RGD(Arg-Gly-Asp)peptides,fibronectin(Fn),fibronectin-like engineered polymer protein(FEPP),extracellular matrix Geltrex,and platelet concentrate.iPSC-MSCs were seeded on five biofunctionalized CPCs:CPC-RGD,CPC-Fn,CPC-FEPP,CPC-Geltrex,and CPC-Platelets.iPSC-MSCs on biofunctional CPCs had enhanced proliferation,actin fiber expression,osteogenic differentiation and mineralization,compared to control.Cell proliferation was greatly increased on biofunctional CPCs.iPSC-MSCs underwent osteogenic differentiation with increased alkaline phosphatase,Runx2 and collagen-I expressions.Mineral synthesis by iPSC-MSCs on CPC-Platelets was 3-fold that of CPC control.In conclusion,iPSCs showed high potential for bone engineering.iPSC-MSCs on biofunctionalized CPCs had cell proliferation and bone mineralization that were much better than traditional CPC.iPSC-MSC-CPC constructs are promising to promote bone regeneration in craniofacial/orthopedic repairs. Induced pluripotent stem cells (iPSCs) have great potential due to their proliferation and differentiation capability. These objectives of this study were to generate iPSC-derived mesenchymal stem cells (iPSC-MSCs), and investigate iPSC-MSC proliferation and osteogenic differentiation on calcium phosphate Cement (CPC) containing biofunctional agents for the first time. Human iPSCs were derived from marrow CD34 + cells which were reprogrammed by a single episomal vector. iPSCs were cultured to form embryoid bodies (EBs), and MSCs migrated out of EBs.Five biofunctional agents were incorporated into CPC: RGD (Arg-Gly-Asp) peptides, fibronectin (Fn), fibronectin-like engineered polymer protein (FEPP), extracellular matrix Geltrex, and platelet concentrate. iPSC-MSCs were seeded on five biofunctionalized CPCs: CPC -RGD, CPC-Fn, CPC-FEPP, CPC-Geltrex, and CPC-Platelets.iPSC-MSCs on biofunctional CPCs had enhanced proliferation, actin fiber expression, osteogenic differentiation and mineralization, compared to control. Cell pr oliferation was greatly increased on biofunctional CPCs.iPSC-MSCs underwent osteogenic differentiation with more alkaline phosphatase, Runx2 and collagen-I expressions. Mineral synthesis by iPSC-MSCs on CPC-Platelets was 3-fold that of CPC control. In conclusion, iPSCs showed high potential for bone engineering. iPSC-MSCs on biofunctionalized CPCs had cell proliferation and bone mineralization that were much better than traditional CPC. iPSC-MSC-CPC constructs are promising to promote bone regeneration in craniofacial / orthopedic repairs.