Construction of a Microenvironment-Responsive Antibacterial Hydrogel Packed With Immunomodulatory Carbonized Polymer Dots for Periodontitis Treatment From Multiple Perspectives

Periodontitis is an increasingly prevalent oral inflammatory disease, whose treatment faces potent challenges because of recurrent bacterial infections, excessive reactive oxygen species (ROS) production, as well as unrelenting inflammation-induced alveolar bone resorption during the pathological process. Herein, we present the rational design and construction of a multifunctional hydrogel platform composed of the quaternized chitosan/oxidized dextran (QCS/OD) hydrogel component with high bactericidal activity and immunomodulatory carbonized polymer dots from resveratrol (RSV-CPDs) for periodontitis treatment. Such RSV-CPDs@QCS/OD (RCQD) hydrogels exhibit characteristics including shape adaptability, self-healing properties, and pH-responsibility, enabling it to adapt to irregularly shaped periodontal tissues, degrade gradually in the mildly acidic microenvironment of periodontitis, and release immunomodulatory RSV-CPDs in a controlled manner. Significantly, RCQD can effectively suppress the proliferation of bacteria as well as alleviate oxidative stress, and relieve inflammation via activating the Nrf2/NF-κB signaling pathway, ultimately fostering a favorable environment for the regeneration of both the soft and hard periodontal tissue. Overall, this study highlights the great potential of RCQD for treating periodontitis by addressing the practical needs in tissue regeneration.