Injectable hydrogels with ROS-triggered drug release enable the co-delivery of antibacterial agent and anti-inflammatory nanoparticle for periodontitis treatment.

Periodontitis, a chronic inflammatory disease caused by bacteria, is characterized by localized reactive oxygen species (ROS) accumulation, leading to an inflammatory response, which in turn leads to the destruction of periodontal supporting tissues. Therefore, antibacterial, scavenging ROS, reducing the inflammatory response, regulating periodontal microenvironment, and alleviating alveolar bone resorption are effective methods to treat periodontitis. In this study, we developed a ROS-responsive injectable hydrogel by modifying hyaluronic acid with 3-amino phenylboronic acid (PBA) and reacting it with poly(vinyl alcohol) (PVA) to form a borate bond. In addition, the ROS-responsive hydrogel encapsulated the antibacterial agent minocycline hydrochloride (MH) and Fe-Quercetin anti-inflammatory nanoparticles (Fe-Que NPs) for on-demand drug release in response to the periodontitis microenvironment. This hydrogel (HP-PVA@MH/Fe-Que) exhibited highly effective antibacterial properties. Moreover, by modulating the Nrf2/NF-κB pathway, it effectively eliminated ROS and promoted macrophage polarization to the M2 phenotype, reducing inflammation and enhancing the osteogenic differentiation potential of human periodontal ligament stem cells (hPDLSCs) in the periodontal microenvironment. Animal studies showed that HP-PVA@MH/Fe-Que significantly reduced alveolar bone loss and enhanced osteogenic factor expression by killing bacteria and inhibiting inflammation. Thus, HP-PVA@MH/Fe-Que hydrogel had efficient antibacterial, ROS-scavenging, anti-inflammatory, and alveolar bone resorption-alleviation abilities, showing excellent application potential for periodontitis healing.