Reconstructing large, inflammatory maxillofacial defects using stem cell-based therapy faces challenges from adverse microenvironments, including high levels of reactive oxygen species (ROS), inadequate oxygen, and intensive inflammation. Here, inspired by the reaction mechanisms of intracellular antioxidant defense systems, we propose the de novo design of an artificial antioxidase using Ru-doped layered double hydroxide (Ru-hydroxide) for efficient redox homeostasis and maxillofacial bone regeneration. Our studies demonstrate that Ru-hydroxide consists hydroxyls-synergistic monoatomic Ru centers, which efficiently react with oxygen species and collaborate with hydroxyls for rapid proton and electron transfer, thus exhibiting efficient, broad-spectrum, and robust ROS scavenging performance. Moreover, Ru-hydroxide can effectively sustain stem cell viability and osteogenic differentiation in elevated ROS environments, modulating the inflammatory microenvironment during bone tissue regeneration in male mice. We believe this Ru-hydroxide development offers a promising avenue for designing antioxidase-like materials to treat various inflammation-associated disorders, including arthritis, diabetic wounds, enteritis, and bone fractures.
