Chen‐Jie YanSu‐Rung YangYI-CHEUN YEH2024-07-312024-07-312024-07-0418614728https://www.scopus.com/record/display.uri?eid=2-s2.0-85197871907&origin=resultslisthttps://scholars.lib.ntu.edu.tw/handle/123456789/720061Combining exogenous and endogenous antibacterial mechanisms has been demonstrated to enhance therapeutic efficacy significantly. This study constructs an innovative type of exogenous and endogenous antibacterial nanocomposite hydrogels with injectable dual-crosslinked networks and dual-stimuli responsiveness. The primary network establishes imine bonds between the functionalized dextran featuring norbornenes and aldehydes (NorAld-Dex) and the quaternized chitosan (QCS). The imine bonds provide self-healing, injectability, and pH-responsiveness to the hydrogel network. The secondary network is established by integrating thiolated mesoporous silica-coated titanium dioxide nanoparticles (TiO2@MS-SH) into the hydrogel network via an ultrasound-activated thiol-norbornene reaction with NorAld-Dex. The microstructures and properties of NorAld-Dex/QCS/TiO2@MS-SH hydrogels can be fine-tuned by adjusting the sonication time to increase the amount of thiol-norbornene crosslinks in the network. Effective antibacterial performance of NorAld-Dex/QCS/TiO2@MS-SH hydrogels at low pH has been demonstrated with the synergistic effect of the acid-induced dissociation of the hydrogel network, protonated QCS, and the reactive oxygen species (ROS) generated by TiO2@MS-SH nanoparticles under ultrasound irradiation. In summary, NorAld-Dex/QCS/TiO2@MS-SH nanocomposite hydrogel is an advanced dual stimuli-responsive antibacterial platform with customizable microstructures and properties, offering great potential for biomedical applications.falseNanoparticlesOrganic-inorganic hybrid compositesRadical reactionsSchiff basesjournal article10.1002/asia.2023011512-s2.0-85197871907