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In the domain of bone tissue engineering, the quest for suitable bone replacement materials that circumvent the limitations of metallic orthopedic implants is of paramount importance. Metallic implants, despite their wide application and success in orthopedic surgery, are often compromised by inadequate osteoconductive properties and risks of surface corrosion and infection, which can lead to tissue damage and fractures with consequent residual distortion. This study introduces novel bio-nano composite scaffolds fabricated utilizing nanosized fillers--8 mol% CaO-PSZ (partially stabilized zirconia) and TiO2 (titanium dioxide)--embedded within an HDPE (high-density polyethylene) matrix for potential orthopedic applications. The bio-nano composites were formed under varying compression pressures (29, 114 MPa) and a constant temperature of 150° for a duration of 15 minutes, resulting in disk-shaped specimens with a diameter of 14.7 mm and heights ranging from 7 to 10 mm. The aim was to determine the optimal thermal and physical properties of these hybrid composites (TiO2-CaO-PSZ/HDPE) for their use as bone substitutes. Characterization of the scaffolds was conducted via three distinct imaging modalities: Fourier transform infrared spectroscopy (FTIR) for chemical structure elucidation, atomic force microscopy (AFM) for topographical analysis, and differential scanning calorimetry (DSC) for thermal property assessment. The analysis confirmed that the incorporation of nanoparticle fillers into the HDPE matrix resulted in enhanced structural stability and mechanical interlocking at the atomic level. Furthermore, improvements in thermal behavior and crystallization degree were observed in direct correlation with the applied hot-press pressure and the presence of ceramic fillers. [ABSTRACT FROM AUTHOR]