Scaffold creates a chance for bone growth and facilitates cell adhesion, growth and differentiation in orthopedic surgeries. Designing scaffold with adequate porous geometry and suitable compressive strength is debatable among biomaterial engineers and clinical orthopedic surgeons. Therefore, in this study we fabricate a novel porous hydroxyapatite-wollastonite reinforced with 0, 5, 10, and 15 wt% alumina nanoparticles (ALN: 40-80 nm) for bone substitute. In the current work, a porous cylindrical scaffold (6 mm x 10 mm) fabricated with space holder (SH) technique using sodium bicarbonate (NaHCO3) as a porous agent. The porosity, compressive strength and the biological behavior of the porous samples were investigated using standard mechanical and biological testing. After making the specimen, scanning electron microscope (SEM) and X-ray diffraction (XRD) analysis were performed to verify the accuracy of the nanomaterial's properties. The mechanical and biological analysis (swelling & water absorption) showed that the sample with 10 wt% alumina nanoparticles (ALN) had both proper compression strength vs. porosity percentage and bioactivity response. The molecular modeling for predicting the elastic modulus of bio-nanocomposite were performed and the results were close to the experimental values. The obtained result, indicated that compressive strength increased from 2.8 to 3.5 MPa with 49% to 61% porosity value. The sample with 10 wt% ALN and wollastonite showed clinical applications of these composites as a bone-substitute. (C) 2019 Elsevier B.V. All rights reserved.