Oxygen Vacancy‐Enriched Platinum Single‐Atom Nanozyme Wrapped in Nanoislands: Unlocking Catalytic Activity and Reprogramming Redox Microenvironment for Osteonecrosis Repair

ABSTRACT Excessive accumulation of reactive oxygen species (ROS) impairs bone regeneration and angiogenesis in steroid‐induced osteonecrosis of the femoral head (SONFH), yet current antioxidant therapies remain limited by low catalytic efficiency and short duration. Single‐atom nanozymes (SANs), with their well‐defined structures and maximal atomic efficiency, show great potential for treating ROS‐induced diseases by mimicking natural enzymes. However, the strong binding between transition metal sites and electron‐donating intermediates (e.g., O*, OH*, OOH*) creates high energy barriers, limiting their catalytic activities. Herein, single‐atomic platinum is successfully embedded into CeO _2‐x to form CeO _2‐x /Pt SANI, which enhanced catalytic activity via an “island‐sea” synergistic effect. Leveraging the unique charge‐transfer structures and confinement effect of nanoislands, CeO _2‐x /Pt SANI exhibits superior enzymatic activities than CeO ₂ , attribute to the island‐sea synergistic effect that facilitates strong electron transfer, as proved by density functional theory (DFT) calculations. DFT calculations further demonstrate that Pt incorporation increases oxygen vacancies and tunes the d‐band center toward the Fermi level, facilitating ROS adsorption and accelerating redox reactions. Single‐cell sequencing and experimental results confirm that CeO _2‐x /Pt SANI reprograms the oxidative microenvironment, leading to significant therapeutic effects in SONFH. This study provides insights into the rational design of an advanced “island‐sea” structured single‐atom nanozyme to optimize the catalytic activity.