Osteoinductive biornaterials are attractive for repairing a variety of bone defects, and biomimetic strategies are useful toward developing bone scaffolds with such capacity. Here, a multiple biomimetic design was developed to improve the osteogenesis capacity,of composite scaffolds consisting of hydroxyapatite nanoparticies (HA) and silk fibroin (SF). SF nanofibers and water-dispersible HA nanoparticles were blended to prepare the nanoscaled composite scaffolds with a uniform distribution of HA. with a high HA content (40%), imitating the extracellular matrix (ECM) of bone. Bone morphogenetic protein-2 (BMP-2) Was loaded in the SF scaffolds and HA to tune BMP-2 release In vitro studies showed the preservation of BMP-2 bioactivity in the composite scaffolds, and programmable sustained release was achieved through adjusting the ratio of BMP-2 loaded on SF and HA. In vitro and in vivo osteogenesia studies demonstrated that the composite scaffolds showed. improved Osteogenesis, capacity under suitable BMP-2 release conditions, significantly better than that of BMP-2 loaded SF HA composite scaffolds reported previously. Therefore, these biominietic SF HA nanoscaled Scaffolds with tunable BMP-2 delivery provide preferable microenvironrnents for bone regeneration.