Abstract
The treatment of large bone defects remains a significant clinical challenge due to the limitations of current grafting techniques, including donor site morbidity, restricted availability, and suboptimal integration. Recent advances in 3D bioprinting technology have enabled the fabrication of structurally and functionally optimized scaffolds that closely mimic native bone tissue architecture. This review comprehensively examines the latest developments in 3D-printed scaffolds for bone regeneration, focusing on three critical aspects: (1) material selection and composite design encompassing metallic; (2) structural optimization with hierarchical porosity (macro/micro/nano-scale) and biomechanical properties tailored; (3) biological functionalization through growth factor delivery, cell seeding strategies and surface modifications. We critically analyze scaffold performance metrics from different research applications, while discussing current translational barriers, including vascular network establishment, mechanical stability under load-bearing conditions, and manufacturing scalability. The review concludes with a forward-looking perspective on innovative approaches such as 4D dynamic scaffolds, smart biomaterials with stimuli-responsive properties, and the integration of artificial intelligence for patient-specific design optimization. These technological advancements collectively offer unprecedented opportunities to address unmet clinical needs in complex bone reconstruction.