Bacteria-responsive injectable hydrogel based on quaternized chitosan for real-time infection monitoring and synergistic NIR-II photodynamic/photothermal anti-infection therapy

Green-Synthesized Scaffolds for Smart Hydrogels. Green-synthesized quaternized chitosan (QCS) represents an ideal macromolecular backbone for constructing functional hydrogels, driven by its structural tunability, excellent aqueous solubility, and intrinsic cationic nature. Unlike native chitosan, the targeted introduction of quaternary ammonium groups endows QCS with a permanent positive charge. This modification not only enhances its degradation but also confers superior antibacterial efficacy and mucoid hesiveness. By leveraging QCS as a versatile scaffold to rationally design polysaccharide-based hydrogels with tailored physicochemical and biological profiles, this work provides a sustainable and highly effective platform for advancing next-generation bioactive materials. • Sol-Gel transition and enhanced antibacterial performance. Macrocyclic host TEBox markedly improves EGCG’s (guest) water solubility and antibacterial effect via host-guest interactions. It also effectively drives the Sol-Gel transition of QCS-EC Sol, finally enabling the preparation of bacteria-responsive multifunctional injectable hydrogel (MQCEC-TEB Gel). This gel has excellent skin adhesion and promotes cell proliferation and tissue regeneration. • Real-Time, Visual Infection Monitoring. Key innovation: a chaotropic effect-based bacteria-responsive agent (TEBox-B 12 ). When exposed to bacteria, TEBox-B 12 undergoes in situ reduction to generate stable organic radicals, causing rapid visible color change (pale yellow to deep purple). This provides a revolutionary tool for early, non-invasive, real-time infection diagnosis. • Synergistic Anti-infection Therapy for Deep Tissue. Radicals from the above reaction not only enable color development but also have strong NIR-II absorption, allowing the hydrogel to achieve deep-tissue photothermal (PTT) and photodynamic (PDT) antibacterial therapy. NIR-II light penetrates deeper into tissue, overcoming traditional phototherapy limitations. This study presents a new smart dressing and "diagnosis-and-therapy integration" strategy, offering a new paradigm for managing invasive infection wounds. Smart hydrogel dressings with sustained wound-healing promotion and infection-monitoring capabilities demonstrate significant potential for invasive infection wound repair. Inspired by mussels, a highly adhesive and multifunctional injectable antibacterial hydrogel dressing (MQCEC-TEB Gel) was developed for wound repair and real-time infection monitoring, comprising a viscous hydrogel scaffold (QCS-EC) and a bacteria-responsive agent (TEBox-B 12 ) crosslinked via host-guest interaction. The epigallocatechin gallate (EGCG) was incorporated into quaternized chitosan (QCS) enhancing the viscosity of QCS and forming the QCS-EC scaffold by hydrogen bonding, providing sustained antibacterial activity and promoting wound-healing. Meanwhile, the bacteria-responsive agent TEBox-B 12 self-assembles via a chaotropic effect between box-shaped quaternized pyridinium salt (TEBox) and the superchaotropic anion B 12 H 12 2− . Upon bacterial exposure, TEBox-B 12 underwent in situ reduction, generating stable organic radicals that trigger a rapid visible color change from pale yellow to deep purple for real-time infection monitoring. The resulting radicals also exhibit strong NIR-II absorption, enabling deep-tissue photothermal (PTT) and photodynamic (PDT) antibacterial therapy. The host-guest interactions between TEBox of TEBox-B 12 and EGCG on QCS-EC improves the water solubility and antibacterial efficiency of EGCG, facilitating Sol-Gel transition to form the injectable MQCEC-TEB Gel platform. This system synergistically integrates host-guest interaction, NIR-II PDT, and PTT to efficiently eradicate deep-tissue bacteria and promote wound healing, offering a novel multimodal strategy for early diagnosis, non-invasive monitoring and treatment of invasive infection wounds.