Objective The objective of this study is to compare the effects of nano-hydroxyapatite/collagen/ poly (L-lactide) (nHAC/PLA) andbeta-tricalcium phosphate (β-TCP) on the attachment, proliferation and osteogenic differentiation of rabbit dental pulp stem cells (DPSCs).Methods We compared the absorption water rate and the protein adsorption rate of two scaffoldsand the characterization of DPSCs cultured on the culture plate and both scaffolds under osteogenic differentiation media (ODM) treatment.The constructs were then implanted subcutaneously into the back of severely combined immunodeficient (SCID) mice for 8 and 12 weeks to compare their bone formation capacity.ResultsThe results showed that the ODM-treated DPSCs expressed osteocalcin, bone sialoprotein, type Ⅰ collagenand osteopontin by immunofluorescence staining.Positive alkaline phosphatase (ALP) staining, calcium deposition and calcium nodules were also observed on the ODM-treated DPSCs.The absorption water rate and protein adsorption rate of nHAC/ PLA was significantly higher than β-TCP.The initial attachment of DPSCs seeded onto nHAC/PLA was significantly higher than that onto β-TCP; and the proliferation rate of the cells was also significantly higher than that of β-TCP on 1, 3 and 7 days of cell culture.The ALP activity, calcium/phosphorus content and mineral formation of DPSCs+β-TCP were significantly higher than DPSCs+nHAC/PLA.When implanted into the back of SCID mice, nHAC/PLA alone had no new bone formation, newly formed mature bone and osteoid were only observed in β-TCP alone, DPSCs+nHAC/PLA and DPSCs+β-TCP.The percentage of total bone formation area had no difference between DPSCs+β-TCP and DPSCs+nHAC/PLA at each time point, but the percentage of mature bone formation areaofDPSCs+β-TCP was significantly higher than that of DPSCs+nHAC/PLA.Conclusion Our results have provided a further knowledge that scaffold architecture has different influence on the attachment, proliferation and differentiation of cells.