Ros-responsive and scavenging bifunctional hydrogel enables co-delivery of anti-inflammatory agent and osteogenetic nanoparticle for periodontitis treatment

Periodontitis is characterized by local inflammatory response and the resultant alveolar bone resorption. The elevated reactive oxygen species (ROS) level not only aggravates local inflammation but also prohibits osteogenesis. Hence, simultaneously scavenging ROS and triggering the activity of osteoblasts may produce synergism in periodontium regeneration. Herein, we developed an injectable hydrogel system, CC-B-CAPE@CY-NPs, for periodontitis treatment, in which caffeic acid phenethyl ester (CAPE), a naturally-occurring anti-inflammatory ingredient, was caged by aryl borate for ROS-responsive release. Meanwhile, the nanoparticles incorporating Chrysin (CY), another natural product with osteogenetic property, were also coated in the hydrogel. In vitro, the hydrogel was capable of scavenging the excessive ROS and modulating the polarization of M1 macrophages, highlighting its anti-inflammatory potency. In addition, its osteogenetic effect was verified by the increased ALP activity in the hydrogel-treated periodontal ligament stem cells (PDLSCs). Our studies revealed the anti-inflammatory stemmed from its ablation of NF-κB signaling, while the activation of Wnt/β-catenin cascade accounted for its osteogenetic potency. In a rat periodontitis model, the capability of reducing ROS levels, modulating macrophage polarization, and promoting osteogenesis was transformed into the recovery of destructed alveolar bone. All above, the hydrogel possesses great potential as a promising remedy for periodontitis.