Extrusion-based 3D printing of cross-scale porous bone scaffolds and their micro-topological structures for bone...

Extrusion-based 3D printing has emerged as a pivotal technique for fabricating bone scaffolds; however, conventional approaches are constrained by nozzle-resolution limitations (0.1 mm), resulting in merely cm- to mm-scale dual-scale architectures. Recent advances overcome this barrier through three modified extrusion 3D printing strategies: (1) cryogenic-field-assisted extrusion (cryogenic 3D printing) utilizes ice crystals as natural porogens; (2) sacrificial/particle-leaching extrusion (sacrificial 3D printing) creates internal micropores within strands; (3) particle-sintered extrusion printing (ceramic sintering 3D printing) generates micron-scale surface textures on printed filaments. These innovations enable tri-scale scaffold construction (cm-mm-μm) that better mimics the hierarchical organization of natural bone. This review establishes a microstructure-property framework through three critical aspects: First, it analyzes process-structure relationships in these advanced extrusion 3D printing techniques. Second, it systematically evaluates five key microarchitectural determinants of osteogenesis: porosity, pore orientation, embedded nanoparticles, micropattern, and surface roughness. Third, it demonstrates that all five microstructural features (pores as concave curvatures, particles/protrusions as convex curvatures) are fundamentally governed by curvature variations, which directly dictate cellular responses through differential focal adhesion assembly and mechanosensitive signaling. At last, current challenges in resolution-scaling paradoxes, dynamic biointerface engineering, and clinical validation are critically discussed. By correlating extrusion process innovations with microstructural bioactivity principles, this work provides a roadmap for designing truly biomimetic bone regeneration scaffolds.