Sequential Therapy for Bone Regeneration by Cerium Oxide-Reinforced 3D-Printed Bioactive Glass Scaffolds

Rational design of multifunctional biomaterials with customized architecture and on demand bioactivity is of great significance for bone tissue engineering (BTE) in modern society. Herein, a versatile therapeutic platform has been established by integrating cerium oxide nanoparticles (CeO2 NPs) into bioactive glass (BG) to fabricate three-dimensional (3D)-printed scaffolds, achieving a sequential therapeutic effect against inflammation and promoting osteogenesis toward bone defect. The antioxidative activity of CeO2 NPs plays a crucial role in alleviating the oxidative stress upon formation of bone defects. Subsequently, CeO2 NPs exert a promotion effect on the proliferation and osteogenic differentiation of rat osteoblasts through enhancing mineral deposition and alkaline phosphatase and osteogenic gene expression. Strikingly, the incorporation of CeO2 NPs bestows on the BG scaffolds greatly reinforced mechanical properties, improved biocompatibility, adequate cell adhesion, elevated osteogenic capability, and multifunctional performance in a single platform. In vivo studies on the treatment of rat tibial defect confirmed the better osteogenic properties of CeO2-BG scaffolds compared with pure BG scaffolds. Additionally, the employment of the 3D printing technique creates a proper porous microenvironment around the bone defect, which further facilitates the cell in-growth and new bone formation. This report provides a systematic study on CeO2-BG 3D-printed scaffolds prepared by simple ball milling method, achieving sequential and integral treatment in BTE based on a single platform.