Regenerating functional bone tissue in critical-sized defects remains a formidable issue. Bone-tissue engineering (BTE) scaffolds are emerging as potential alternatives to bone transplantation for the repair of bone defects. However, developing BTE scaffolds with unique bone-healing properties and natural bone porous structure is challenging. Herein, we presented a biomimetic scaffold with hierarchical porosity via a solvent casting/particulate leaching method. The scaffold comprises osteoinductive whitlockite (WH) nanoparticles evenly dispersed in a poly(lactic--glycolic acid) (PLGA) matrix. Highly interconnected pores with hierarchical variations are present in the scaffold, enabling superior solution diffusion and compressive strength. Notably, the WH/PLGA scaffold effectively promoted osteoblast differentiation and induced bone formation in rat tibia defects, surpassing the performance of both the hydroxyapatite (HAP)/PLGA scaffold and the PLGA scaffold. This study provides a low-cost, facile, and scalable strategy for fabricating BTE scaffolds with favorable mechanical properties, biocompatibility, and bone repair capability.
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