In this study, the effects of bioactive glass nanoparticles' (nBGs) size and shape incorporated into hydroxyapatite/β-tricalcium phosphate (BCP) scaffolds were investigated. We prepared a highly porous (> 85%) BCP scaffold and coated its surface with a nanocomposite layer consisted of polycaprolactone (PCL) and rod (∼ 153 nm in height and ∼ 29 nm in width) or spherical (∼ 33 nm and 64 nm in diameter) nBGs. Osteogenic gene expression by primary human osteoblast-like cells (HOB) was investigated using quantitative real time polymerase chain reaction (q-RT-PCR). We demonstrated for the first time that in vitro osteogenesis is dramatically affected by the shape of the nBGs, whereby rod shaped nBGs showed the most significant osteogenic induction, compared to spherical particles (regardless of their size). Importantly, the good biological effect observed for the rod shaped nBGs was coupled by a marked increase in the modulus (∼ 48 MPa), compressive strength (∼ 1 MPa) and failure strain (∼ 6%), compared to those for the BCP scaffolds (∼ 4 MPa, ∼ 1 MPa and ∼ 0.5% respectively). The findings of this study demonstrated that the shape of the nBGs is of significant importance when considering bone regeneration.