Research on the Improvement of Oxidative Stress Regulation in Periodontal Ligament Stem Cells and the Promotion of Periodontal Bone Tissue Regeneration by GDF5/ROS-Responsive Degradable Hydrogel.

Periodontitis is a chronic inflammatory disorder characterized by a sustained inflammatory stimulus that creates an oxidative stress microenvironment within periodontal tissues. Under such conditions, elevated levels of reactive oxygen species (ROS) disrupt the structural and functional integrity of periodontal ligament stem cells (PDLSCs), inhibit osteogenic differentiation, and impair the regeneration of periodontal bone defects. Herein, a ROS-responsive degradable hydrogel loaded with growth differentiation factor 5 (GDF5) was developed to target this pathological microenvironment. By incorporating a thioketal (TK) linker that can be cleaved by ROS, the hydrogel reacts with high concentrations of ROS, improving the oxidative stress environment. As the reaction occurs, the hydrogel is degraded, and during this process, GDF5 is successfully released into the microenvironment, then exerts a sustained osteogenic-promoting effect. This study does not simply expose GDF5 to a harmful environment. Instead, our hydrogel first rapidly scavenges high levels of ROS upon sensing them, creating a redox-balanced microenvironment for the cells; subsequently, it releases GDF5 through an ROS-triggered mechanism. This sequential logic of "clearing the environment first, then treating" is designed to ensure that the released GDF5 can function in an optimized and functional microenvironment, thereby maximizing its protective effects and promoting its osteogenic activity.