Self-Monitoring Multifunctional Dual-Responsive Hydrogel For Periodontitis Treatment

To develop a self-monitoring multifunctional hydrogel with antibacterial, anti-inflammatory, and osteogenic properties for periodontitis treatment. A Cu²⁺/indocyanine green (ICG)-loaded hydrogel was synthesized through self-assembly of bovine serum albumin and gelatin. The mechanical properties, chemical composition, and microstructure of the hydrogel were investigated by rheometry, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM). In vitro studies demonstrated its dual-responsive capability to reactive oxygen species (ROS) and near-infrared(NIR) light (808 nm). Antibacterial efficacy was assessed against Porphyromonas gingivalis biofilms, while anti-inflammatory effects were evaluated in murine macrophages (RAW264.7) through phenotypic characterization and cytokine profiling. Osteogenic potential was confirmed by Alizarin Red S staining, alkaline phosphataseactivity, and osteogenic gene expression in bone marrow mesenchymal stem cells. Angiogenic capacity was validated through tube formation and chick chorioallantoic membrane assays. In vivo therapeutic efficacy was tested by 6-week-old male SD rats with periodontitis. The comprehensive therapeutic efficacy was evaluated through micro-CT and histopathological analysis after 4-week intervention. The hydrogel enables ROS/NIR-responsive controlled release of Cu²⁺ while allowing real-time monitoring of Cu²⁺ release kinetics via ICG-mediated fluorescence. This multifunctional hydrogel exhibits significant anti-biofilm formation properties and facilitates macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotype. Furthermore, it enhances both angiogenic and osteogenic capacities, thereby presenting a novel therapeutic strategy for periodontal treatment. We have successfully developed a self-monitoring hydrogel with integrated antibacterial, anti-inflammatory, and periodontal tissue-regenerative functionalities for periodontitis treatment.