摘要： Conventional biphasic calcium phosphate (BCP) bioceramics are facing many challenges to meet the demands of regenerative medicine, and their biological properties are limited to a large extent due to the large grain size in comparison with nanocrystalline of natural bone mineral. Herein, this study aimed to fabricate porous BCP ceramic spheres with nanocrystalline (BCP-N) by combining alginate gelatinizing with microwave hybrid sintering methods and investigated their in vitro and in vivo combinational osteogenesis potential. For comparison, spherical BCP granules with microcrystalline (BCP-G) and commercially irregular BCP granules (BAM, BCP-I) were selected as control. The obtained BCP-N with specific nanotopography could well initiate and regulate in vitro biological response, such as degradation, protein adsorption, bone-like apatite formation, cell behaviors, and osteogenic differentiation. In vivo canine intramuscular implantation and rabbit mandible critical-sized bone defect repair further confirmed that nanotopography in BCP-N might be responsible for the stronger osteoinductivity and bone regenerative ability than BCP-G and BCP-I. Collectedly, due to nanotopographic similarities with nature bone apatite, BCP-N has excellent efficacy in guiding bone regeneration and holds great potential to become a potential alternative to standard bone grafts in bone defect filling applications.