Photothermally Reinforced Quaternary Ammonium-Functionalized Natural Macromolecule-Based Hydrogels for Postextraction Anti-Infection and Immune Microenvironment Modulation

Abstract Extraction sockets are prone to bacterial colonization, which causes alveolar bone resorption and refractory infection. However, conventional biomaterials cannot eliminate pathogenic bacteria and modulate the oral immune microenvironment at the same time. Herein, we constructed a structurally tailored hydrogel (HAQM) with in-network bactericidal activity to achieve mild photothermal synergistic sterilization. Mild hyperthermia (∼42 °C) increases bacterial membrane fluidity and strengthens the contact-killing performance of the hydrogel. In vitro and in vivo biological assays verify its outstanding antibacterial activity, particularly against oral obligate anaerobes, with an antibacterial efficiency reaching 95%. Transcriptomic analysis reveals that the hydrogel destabilizes bacterial membranes, disturbs bacterial metabolic pathways, and suppresses bacterial envelope repair. Benefiting from its interconnected porous architecture and redox-responsive activity, the hydrogel mitigates inflammatory response and promotes M2-type macrophage polarization. This multifunctional integrated platform provides an innovative and clinically translatable therapeutic strategy for the repair of infected oral bone defects.