Objective: It has been proven that acetylsalicylic acid (aspirin), as a kind of classical non-steroidal anti-inflammatory drug, not only has the effect of anti-inflammatory, but also has the function of immunity regulation and mineralization. However, it needs further investigation to study how to delay release of aspirin for a long time and enable to promote bone regeneration. Herein, we demonstrated that the long-term delayed release pattern of aspirin through the construction of microsphere scaffolds is promising to achieve the excellent bone regeneration. Methods: Here we synthesized three kinds of scaffolds as follows: (1) aspirin loaded calcium silicate (CaSiO₃) microsphere (CaSiO₃-aspirin) via simple immersion; (2) aspirin loaded polylactic-co-glycolic acid (PLGA) microsphere (PLGA-aspirin) via oil/water (O/W) emulsion; (3) aspirin loaded PLGA-CaSiO₃ scaffold (PLGA-CaSiO₃-aspirin) via O/W emulsion, optimal morphology and structure of PLGA-CaSiO₃-aspirin scaffold was acquired through modulating the ratio between PLGA and CaSiO₃. Furthermore, spectrophotometer was used to monitor the concentration of the extract of the three scaffolds for different releasing time, including 1, 2, 4, 6, 9, 13, 17, 21, 24, 30, 36, and 45 days, aspirin loading efficiency and its accumulation releasing curves were both achieved according to the concentration of aspirin. Their sustained release effects of aspirin were evaluated eventually. Results: Environmental scanning electron microscope (ESEM) results showed that the surface structure of the three kinds of scaffolds were smooth and had uniform size distribution. In addition, a small amount of PLGA-aspirin microspheres occurred to aggregation, while a small amount of CaSiO₃-aspirin microspheres were broken. Moreover, the PLGA-aspirin microspheres in the PLGA-CaSiO₃-aspirin scaffolds were uniformly adhered to the surface of CaSiO₃ microspheres. The aspirin loadings of CaSiO₃-aspirin, PLGA-aspirin, and PLGA-CaSiO₃-aspirin were (1.06±0.04)%, (7.05±0.06)%, and (6.75±0.18)%, respectively. In addition, their corresponding time for releasing 95% of aspirin was 3, 24, and 36 days, respectively. The releasing time of PLGA-CaSiO₃-aspirin was longer than that of the others and the releasing rate was more stable. Conclusion: The microsphere scaffold of PLGA-CaSiO₃-aspirin composites has excellent delayed-release effect on aspirin, which is promising for using as osteogenic materials.