Functionalized BCP scaffold with cerium oxide nanozymes for synergistic bone regeneration via enhanced osteogenesis and angiogenesis

• A novel CeO 2 -BCP scaffold was fabricated via press-molding and calcination. • CeO2-BCP scaffolds activated the Wnt/β-catenin signaling pathway in MC3T3-E1 cells. • CeO 2 -BCP scaffold promoted HUVECs migration, tube formation, and angiogenesis in vitro and in vivo . • CeO 2 -BCP scaffold promoted synergistic osteogenesis and angiogenesis, accelerating critical-sized bone repair. Oral and maxillofacial bone defects remain a significant clinical challenge. Biphasic calcium phosphate (BCP) is an attractive bone graft material due to its bone-like composition and favorable biocompatibility. Incorporation of cerium oxide nanoparticles (CeO 2 -NPs) offers additional osteogenic and multifunctional benefits for bone regeneration. In this study, CeO 2 -NPs-incorporated BCP porous scaffolds were fabricated via press-molding and calcination. The CeO 2 -BCP scaffolds promoted adhesion, proliferation, migration, and osteogenic differentiation of MC3T3-E1 pre-osteoblasts, the latter of which might be associated with activation of the Wnt/β-catenin signaling pathway. Additionally, the scaffolds stimulated the migration, tube formation, and angiogenesis-related gene expression in human umbilical vein endothelial cells (HUVECs), enhancing their angiogenic potential. In vivo , matrix plug assays in nude mice confirmed excellent biosafety and pro-angiogenic capability. Furthermore, CeO 2 -BCP scaffolds significantly promoted both angiogenesis and osteogenesis, leading to robust bone regeneration in critical-sized defects. Collectively, this biomimetic composite scaffold represents a highly promising strategy for oral and maxillofacial bone repair and offers great potential for clinical translation.