Targeted antibacterial and mesenchymal stem cell-modulatory hydrogel for periodontitis treatment

Mechanical debridement and systemic antibiotics, as current therapeutic modalities for periodontitis, suffer from limitations, including insufficient local efficacy and bacterial resistance. Herein, a dual-mode injectable hydrogel (A-CC-PBA@ZIF-8@CAPE Gel) has been designed and prepared for enhancing the therapeutic efficacy through targeted anti-infection and rectification of the dysregulated mitochondrial function of mesenchymal stem cells (MSCs) in inflammatory state. Both the in vitro antibacterial evaluation and molecular dynamics simulation confirmed the phenyl boronic acid (PBA)-modification boosted the antimicrobial efficacy against periodontal pathogenic bacteria. In addition to the targeted antibacterial efficacy, A-CC-PBA@ZIF-8@CAPE Gel exhibited remarkable capacity to scavenge ROS, ameliorate inflammatory response, relieve oxidative stress, and restore the mitochondrial function of MSCs under inflammatory conditions by activating the SIRT1/p-AMPK/PGC-1α pathway, thereby promoting the osteogenic differentiation of MSCs. In rat periodontitis model, A-CC-PBA@ZIF-8@CAPE Gel markedly reduced bone defects and ROS levels, attenuated inflammation, and restored alveolar bone height, demonstrating robust therapeutic potential in chronic inflammatory conditions. In summary, this study presents a promising therapeutic approach for periodontitis, characterized by targeted antibacterial infection, anti-inflammation, and bone regeneration. • Hydrogel enables targeted antibacterial action against P. gingivalis. • Boronic acid groups capture bacteria and ZIF-8 provides potent bactericidal activity. • Hydrogel scavenges mtROS, alleviating oxidative stress in MSCs under inflammation. • Restores MSC mitochondrial function via SIRT1/p-AMPK/PGC-1α pathway. • Promotes osteogenic differentiation, supporting periodontal tissue regeneration.