Manganese empowered electronic modulated nanocatalysts facilitate bone reconstruction via osteoclastogenesis inhibition and osteogenesis activation bistimulatory strategy

Reactive oxygen species (ROS) mediated redox imbalance stands as an important factor contributing to the pathological bone loss, which is characterized by osteoclast hyperactivation and inflammatory activation. Developing ROS-scavenging nanocatalysts emerges as an intriguing strategy to regulate redox balance and bone homeostasis. Herein, this study reveals that Mn-atom-modulation strategy could introduce oxygen vacancy defects and further regulate electronic structure of CeO₂ nanocatalysts with an increased ratio of Ce³⁺/Ce⁴⁺ (named Mn@CeO₂), which promote electron redistribution and enhance comprehensive ROS-scavenging performances. Consequently, the Mn@CeO₂ nanocatalysts show significant inhibition of osteoclastogenesis activity and ameliorate the inflammatory state through the NF-κB and MAPK pathways. Notably, exogenous supplementation of Mn element can promote the osteogenesis activation through the Wnt/β-catenin pathway. Both in vitro/vivo evaluations, this proposed bistimulatory strategy significantly facilitate pathological bone reconstruction via macrophage polarization, osteoclastogenesis inhibition, and osteogenesis activation. This work not only proposes versatile nanocatalysts for pathological bone therapy but also provides novel solution to develop biocatalytic metal oxides through rational regulation of electronic structure.