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In the present work, bioactive nanoclay-TiO2 (NC-T) bio-nanocomposite scaffolds containing different TiO2 weight fractions are fabricated spacer for bone tissue engineering applications via the space holder technique using NaCl particles as the. The microstructure, surface morphology (porosity) and bioactivity potential of the manufactured bio-nanocomposite scaffolds are examined using scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray fluorescence (XRF), energy dispersive spectroscopy (EDS), and inductively-coupled plasma optical emission spectroscopy (ICP-OES) techniques. The scaffold with optimized mechanical properties is predicted as NC-15wt%T with proper interconnected porosity and micro/macro pore size within the range of 1–2 (μm) and 3–5 (μm), respectively. Also, its mechanical properties including compressive strength, elastic modulus and crystallite size are extracted equal to 5.74 MPa, 438 MPa and 70–120 nm, respectively. The feasibility of the fabricated scaffolds for bioactive bone tissue engineering application (apatite deposition) is also evaluated using simulated body fluid (SBF) and physiological saline (PS) solutions. At the end, the nonlinear bending and vibration characteristics of an axially loaded beam-type bone implant made of the NC-T/NaCl bio-nanocomposite scaffolds are predicted analytically. In general view, the obtained results indicate that the NC-15wt%T/NaCl bio-nanocomposite scaffold may have excellent advantages for future research in bone regenerative applications.