Abstract:

Periodontitis is a chronic inflammatory disease that significantly affects oral health. During its pathological progression， the inflammatory response generates excessive reactive oxygen species （ROS）， which disrupts the stability of the tissue microenvironment and impedes bone tissue repair and regeneration. To address these challenges， mesoporous cerium dioxide （CeO₂） nanocarriers were synthesized via the hydrothermal method， and metformin （MET） was loaded onto them through physical adsorption to construct CeO₂@MET composite nanomaterials. The osteogenic potential of these materials was systematically evaluated. Experimental results demonstrated that CeO₂@MET exhibited a uniform mesoporous structure with a MET loading capacity of （5.61±0.37）% （mass fraction）. It retained the cubic fluorite structure and oxygen vacancies （Ce³⁺content of 12.28%） characteristic of CeO₂， while displaying excellent antioxidant enzyme activity and sustained drug-release properties. At concentrations of ≤100 μg/mL， CeO₂@MET significantly promoted the proliferation and migration of MC3T3-E1 pre-osteoblasts and enhanced their alkaline phosphatase activity expression， thereby confirming its excellent biocompatibility and osteogenic differentiation ability. This study successfully developed a CeO₂@MET nanocomposite system with dual functionalities of efficient ROS scavenging and controlled drug release. This system achieves synergistic effects in ROS scavenging and MET-induced osteogenesis， offering a novel nanomaterial-based strategy for overcoming bone regeneration obstacles in periodontitis. It holds significant promise for applications in periodontal tissue engineering， combining anti-inflammatory regulation with highly efficient osteogenic activity.

Key words: Cerium dioxide, Metformin, Mesoporous, Reactive oxygen species scavenging, Osteogenic activity