G-quartet driven adaptive hydrogels that integrate constitutional dynamics for antibacterial action and tissue repair

We report a nucleic acid inspired constitutional dynamic hydrogel (G4TZ) self-assembled from guanosine, a phenylboronic acid, and a thiazole peptide through dynamic covalent linkages formed by boronate ester and imine bonds, together with supramolecular interactions involving π-π stacking and K⁺-induced G-quartet formation. The resulting transparent and injectable hydrogel exhibits shear-thinning and pH-responsive behavior. G4TZ displays potent antibacterial activity against multidrug-resistant Streptococcus pneumoniae through reactive oxygen species generation, membrane disruption, DNA fragmentation, and biofilm inhibition, while maintaining excellent cytocompatibility. Furthermore, it accelerates re-epithelialization and promotes wound healing both in vitro and in vivo. This dynamic covalent and supramolecular system unites molecular design with biological function, offering strong translational potential for antimicrobial and regenerative medicine. More broadly, this work demonstrates reaction-driven multicomponent self-assembly as a general strategy to engineer multifunctional biomaterials with enhanced stability, biocompatibility, and therapeutic efficacy.