Injectable Thermosensitive Gel CH‐BPNs‐NBP for Effective Periodontitis Treatment through ROS‐Scavenging and Jaw Vascular Unit Protection

Abstract Periodontitis, a prevalent inflammatory condition in the oral cavity, is closely associated with oxidative stress‐induced tissue damage mediated by excessive reactive oxygen species (ROS) production. The jaw vascular unit (JVU), encompassing both vascular and lymphatic vessels, plays a crucial role in maintaining tissue fluid homeostasis and contributes to the pathological process in inflammatory diseases of the jaw. This study presents a novel approach for treating periodontitis through the development of an injectable thermosensitive gel (CH‐BPNs‐NBP). The gel formulation incorporates black phosphorus nanosheets (BPNs), which are notable for their ROS‐scavenging properties, and dl‐3‐n‐butylphthalide (NBP), a vasodilator that promotes lymphatic vessel function within the JVU. These results demonstrate that the designed thermosensitive gel serve as a controlled release system, delivering BPNs and NBP to the site of inflammation. CH‐BPNs‐NBP not only protects macrophages and human lymphatic endothelial cells from ROS attack but also promotes M2 polarization and lymphatic function. In in vivo studies, this work observes a significant reduction in inflammation and tissue damage, accompanied by a notable promotion of alveolar bone regeneration. This research introduces a promising therapeutic strategy for periodontitis, leveraging the unique properties of BPNs and NBP within an injectable thermosensitive gel.