Molybdenum nanodots reprogram inflammatory-driven osteolysis via bone immune remodeling

The translational potential of nanomedicines largely depends on compositional simplicity and scalable synthesis, with structurally intricate systems (e.g., hybrid composites) often struggling in manufacturing standardization. Single-element nanosystems bypass these limitations through inherent biosafety and bioactivity tunability. Herein, molybdenum nanodots (MoNDs), which synthesized via a facile and reproducible ultrasonic exfoliation method, were designed to address implant-associated osteolysis. These mono-component MoNDs displayed robust reactive oxygen species (ROS) scavenging and biocompatibility alongside recovering mitochondrial function to alleviate oxidative stress and curbing NF-κB-mediated M1 macrophage polarization. The MoNDs further regulated bone remodeling by suppressing osteoclastogenesis through NFATc1/CTSK downregulation and promoting osteogenic differentiation. In vivo evaluations using a titanium particle-induced osteolysis model revealed that the MoNDs effectively attenuated pathological bone loss, improved trabecular integrity, and rebalanced bone metabolic markers. Collectively, this work positions MoNDs as a clinically viable nanotherapeutic that harnesses elemental simplicity to resolve inflammation-driven osteolytic disorders, bridging material design with translational orthopedics.