Nanozyme‐Integrated 3D‐Printed Gradient Scaffold Rescues Redox Homeostasis for Enhanced Osteochondral Repair

Osteochondral defects pose a significant clinical challenge due to their limited capacity for self‐repair. Although arthroplasty is commonly performed, serious complications remain a major concern. In this study, a novel ultrasmall Prussian blue (USPB) nanozyme‐functionalized 3D‐printed gradient antioxidant scaffold was fabricated. Osteogenic and antisenescence hydrogels were incorporated into the subchondral and cartilage regions, respectively. The scaffold's performance, including biocompatibility, effects on cellular senescence, osteogenic differentiation, and underlying mechanisms, was evaluated through a series of in vitro and in vivo assays. The composite scaffold effectively scavenged reactive oxygen species (ROS) and enhanced the endogenous antioxidant defense system in both C28 chondrocytes and rat bone marrow stem cells (rBMSCs). Mechanistically, the cartilage region of the scaffold maintained cellular homeostasis by upregulating GPX4 expression, inhibiting ferroptosis, and bolstering antisenescence activity. In the subchondral region, the scaffold promoted osteogenic differentiation and mineralization of rBMSCs by activating the PI3K‐AKT signaling pathway. This study presents a biomimetic scaffold that demonstrates significant potential for osteochondral repair while systematically elucidating the mechanisms governing cellular homeostasis. These findings provide a foundation for the development of next‐generation multifunctional tissue engineering platforms.