A Multifunctional Therapeutic Platform: Ce/Zn/Sr-Doped Mesoporous Bioactive Glass Nanoparticles for Bone Repair

Mesoporous bioactive glass nanoparticles (MBGNs) are promising for bone tissue engineering; however, surgical site infection and oxidative stress often compromise regeneration. To address this, MBGNs co-doped with cerium (Ce), zinc (Zn), and strontium (Sr) were synthesized using a microemulsion-assisted sol-gel route (xCe-yZn-Sr-MBGNs; x = 0, 1, 2; y = 0, 0.5, 1). The resulting spherical nanoparticles (150-200 nm) exhibited a mesoporous structure with a specific surface area of (~340-425 m²/g), sustained ion release, and apatite formation in simulated body fluid. In vitro evaluations with MC3T3-E1 pre-osteoblasts demonstrated dose-dependent cytocompatibility, specifically in the co-doped formulations; however, higher Ce concentrations (2Ce-yZn-Sr-MBGNs) reduced viability following prolonged exposure. Crucially, the 1Ce-1Zn-Sr-MBGNs significantly enhanced osteogenic differentiation, as evidenced by a two-fold increase in osteogenic marker gene expression and a ~45% increase in calcium mineral deposition compared to undoped MBGNs within 14 days. Moreover, these particles accelerated cell migration, achieving ~70% scratch-wound closure within 24 h. Furthermore, 1Ce-1Zn-Sr-MBGNs displayed strong radical scavenging capacity and potent antibacterial activity against <i>S. aureus</i> and <i>P. aeruginosa</i>. These findings indicated that 1Ce-1Zn-Sr-MBGNs exhibited multiple therapeutic effects, including antibacterial, radical-scavenging, and osteogenic effects. By optimizing dopant ratios, these multifunctional nanomaterials emerge as promising candidates for next-generation bone grafts or implant coatings. Within the scope of this study, they demonstrated the capacity to simultaneously address three critical challenges in bone healing: controlling infection, mitigating oxidative stress, and promoting mineralized tissue formation. While these in vitro results provide a robust foundation, further in vivo validation is warranted to confirm their efficacy within complex physiological environments.