Antibacterial And Immunomodulatory Chitosan Nanohydrogels For Periodontitis Therapy

This study developed a hydrogel-dendritic nanogel composite drug delivery system with antibacterial and immunomodulatory functions for periodontitis treatment. The chitosan-based nanogel Gel-BCN-DNG@Mino was synthesized by uniformly mixing and stirring chitosan (CS), β-glycerophosphate (β-GP)/sodium bicarbonate (NaHCO3)-baicalin (BCN) solution, minocycline-dendritic nanogel(DNG@Mino),and sodium alginate (SA) in a ratio of 10:5:3:2.The β-GP/NaHCO₃-BCN solution was prepared by dissolving BCN in a β-GP/NaHCO₃ solution (with β-GP at a mass fraction of 33%), ensuring a final BCN concentration of 200 μg/mL in the hydrogel. The crosslinking properties of DNG are controlled by thiol-ene coupling chemistry, and its primary component is a dendritic-linear-dendritic (DLD) block copolymer. The DLD copolymer is synthesized via pseudo-polycondensation using bifunctional 20k PEG and 2,2-bis(hydroxymethyl)propionic acid (bis-MPA) monomers.The optimal mass ratio of Mino to DNG was 1:8. Here, we engineered a multifunctional chitosan-based hydrogel incorporating DNG@mino and baicalin within a porous polymeric matrix for dual antibacterial and anti-inflammatory therapy. This platform enabled simultaneous baicalin delivery with sustained minocycline release. Notably, baicalin potentiated minocycline's antibacterial efficacy in vitro, allowing dose reduction. Flow cytometry revealed Gel-BCN-DNG@Mino effectively suppressed M1 macrophage polarization. The dual-therapeutic nanohydrogel was validated as an effective drug delivery system against periodontal pathogens and inflammation, simultaneously inhibiting alveolar bone loss and enhancing periodontal tissue repair.