階層的な骨形成PLA足場の工学のための熱誘起相分離と組み合わせた3D印刷

Accelerated population aging and rising incidence of bone defects have intensified the need for advanced bone regeneration strategies. While tissue-engineered scaffolds fabricated via 3D printing offer promising alternatives to conventional grafts, most techniques fail to replicate the multi-scale fibrous architecture of native bone extracellular matrix, limiting their biofunctionality. To address this, we developed a hybrid manufacturing strategy integrating low-temperature thermally induced phase separation with extrusion-based 3D printing of polylactic acid (PLA) scaffolds. By optimizing solvent ratios (THF: DMF = 3:1) and freezing temperatures (-196 °C-4 °C), we produced scaffolds with tunable micro-nano fibrous surfaces and macroporous structures. Key findings revealed that scaffolds processed at -196 °C (PLA-196) exhibited the highest porosity (pore size: 6.01 ± 2.06 μm), superior hydrophilicity, and enhanced compressive modulus. These scaffolds significantly promoted BMSC adhesion, proliferation, and osteogenic differentiation via activation of Macf1-mediated pro-osteogenic signaling pathways, leading to elevated expression of Runx2, Ocn, and Col-I. In vivo, PLA-196 scaffolds accelerated cranial defect healing, achieving 62 % bone volume fraction and robust vascularization within 8 weeks. This study demonstrates a scalable, biocompatible platform for fabricating hierarchically structured bone scaffolds that bridge the gap between structural complexity and biological efficacy, offering significant potential for clinical translation in regenerative medicine.