ObjectiveTo explore the role of a three-dimensional (3D)-printed porous titanium alloy scaffold (3D scaffold) in the osteogenic differentiation of human adipose-derived mesenchymal stem cells (hADMSCs) and the underlying mechanism.MethodshADMSCs were divided into control and 3D scaffold groups. The osteogenic differentiation of hADMSCs and expression of osteogenic makers were estimated. Based on the information from published articles, five candidate circular RNAs were selected, and among them, hsa_circ_0019142 showed the most promising results. Finally, control group cells were overexpressed or silenced with the hsa_circ_0019142. Then, Alizarin red S (ARS) staining, calcium content analysis and estimation of alkaline phosphatase (ALP), osteocalcin (OCN), runt-related transcription factor 2 (RUNX2), and collagen-1 (COL1) were performed to evaluate the role of hsa_circ_0019142 on osteogenic differentiation.ResultsOsteogenic differentiation of the hADMSCs was significantly higher in the 3D scaffold group than in the control group, as evidenced by ARS staining, increased calcium concentration, and elevated expression of above four osteogenic factors. qPCR revealed that the expression of hsa_circ_0019142 was significantly higher in the 3D scaffold group. Overexpression of hsa_circ_0019142 promoted the osteogenic differentiation of hADMSCs, while knockdown of hsa_circ_0019142 caused the opposite results.ConclusionThe 3D-printed scaffold promoted osteogenic differentiation of hADMSCs by upregulating hsa_circ_0019142.