A novel hydrogel microsphere (P-GelMA-Ce@BMSCs) was developed to promote bone regeneration by capturing cerium ions (Ce³⁺) and incorporating bone marrow mesenchymal stem cells (BMSCs). The microsphere was fabricated using microfluidic technology and non-covalent coordination reactions, resulting in a porous structure that allows for controlled release of Ce³⁺. The Ce³⁺ ions promote osteogenic differentiation of BMSCs, angiogenesis of endothelial cells, and mineral deposition, which are essential for bone repair. The microsphere also supports cell adhesion, proliferation, and extracellular matrix (ECM) formation, enhancing the overall regenerative capacity. In vitro experiments demonstrated that the microsphere significantly enhanced osteogenic differentiation and angiogenesis compared to control groups. In vivo evaluation using a rat calvarial defect model showed improved bone regeneration, with increased bone volume, mineral density, and vascularization. The microsphere's ability to release Ce³⁺ in a controlled manner, combined with its biocompatibility and structural properties, makes it a promising candidate for bone tissue engineering. The study highlights the potential of metal ion-loaded biomaterials as effective carriers for controlled release of therapeutic ions, offering a novel approach for treating bone defects.A novel hydrogel microsphere (P-GelMA-Ce@BMSCs) was developed to promote bone regeneration by capturing cerium ions (Ce³⁺) and incorporating bone marrow mesenchymal stem cells (BMSCs). The microsphere was fabricated using microfluidic technology and non-covalent coordination reactions, resulting in a porous structure that allows for controlled release of Ce³⁺. The Ce³⁺ ions promote osteogenic differentiation of BMSCs, angiogenesis of endothelial cells, and mineral deposition, which are essential for bone repair. The microsphere also supports cell adhesion, proliferation, and extracellular matrix (ECM) formation, enhancing the overall regenerative capacity. In vitro experiments demonstrated that the microsphere significantly enhanced osteogenic differentiation and angiogenesis compared to control groups. In vivo evaluation using a rat calvarial defect model showed improved bone regeneration, with increased bone volume, mineral density, and vascularization. The microsphere's ability to release Ce³⁺ in a controlled manner, combined with its biocompatibility and structural properties, makes it a promising candidate for bone tissue engineering. The study highlights the potential of metal ion-loaded biomaterials as effective carriers for controlled release of therapeutic ions, offering a novel approach for treating bone defects.