Nano MgO2 and pabocinib loaded hydrogel accelerate growth plate repair by releasing oxygen and inhibiting apoptosis

The growth plate plays a critical role in longitudinal bone growth in children. Growth plate injuries frequently lead to the formation of bone bridges at the lesion site, which could result in angular deformities or growth disturbances such as limb shortening. At the end of adolescence, the mechanisms by which growth plate injury leads to bone bridge formation remain unclear. To date, mechanistic understanding of bone bridge formation following growth plate injury is typically divided into three temporal phases-inflammatory, fibrogenic, osteogenic and bone-bridge maturation repair phases - during which excessive hypoxia accompanies the process. However, precise elucidation of the underlying mechanisms remains incomplete. Herein, integrating single-cell sequencing data, we demonstrate a relationship between CDK6 and apoptosis following growth plate injury. CDK6 promotes ROS generation and inhibits HIF-2α degradation, thereby facilitating p53 upregulation and inducing apoptosis of growth plate chondrocytes. In this study, we developed a ROS responsive hydrogel system composed of polyvinyl alcohol (PVA), sodium borate (Na 2 B 4 O 7 ), hyaluronic acid (HA), and magnesium peroxide (MgO 2 ). This system encapsulates palbociclib to inhibit of CDK6 and Hypoxiaand reverse chondrocyte apoptosis. Radiographic and histological analyses confirmed that the palbociclib-loaded hydrogel system successfully reconstructed the growth plate architecture and reduced limb length discrepancies. This study demonstrates the development of the ROS-responsive oxygen-releasing hydrogel loaded with pabocinib as a therapeutic approach to mitigate chondrocyte apoptosis in growth plate injury.