<p>Bone loss resulting from trauma, disease, or tumors significantly compromises patients’ quality of life. Current treatment strategies present limitations related to graft availability, immune rejection, and the risk of disease transmission. In this context, the development of hybrid scaffolds that mimic the hierarchical architecture of bone tissue represents a promising alternative, combining polymers with complementary properties. Polylactic acid (PLA) provides biocompatibility and mechanical strength, resembling the cortical bone structure, while polycaprolactone (PCL) offers flexibility and mimics the trabecular region. This design enables precise control over scaffold geometry, pore size, and overall porosity through fused deposition modeling (3D printing) and salt leaching to reproduce cortical- and trabecular-like regions. Physicochemical properties were characterized using scanning electron microscopy (SEM), pore size analysis, Fourier-transform infrared spectroscopy (FTIR), and porosity measurements. Mechanical performance was evaluated through compression testing, while biological activity was assessed via cell viability assays, alkaline phosphatase (ALP) activity, and Alizarin Red (AR) staining. PLA scaffolds exhibited a compact structure with well-aligned filaments, whereas PCL scaffolds demonstrated a highly porous and interconnected architecture. FTIR results confirmed the absence of chemical interactions between the polymers, preserving their individual properties, and compression tests indicated mechanical strength within the range reported for trabecular bone. Biological assays revealed a progressive increase in cell viability, ALP activity, and mineralization over time, demonstrating that both scaffold regions provided a favorable microenvironment for osteoblastic activity and highlighting the potential of hybrid PLA/PCL scaffolds as biomimetic platforms with region-specific structural characteristics for bone tissue engineering applications.</p> Graphical abstract <p></p>