G-quartet driven G4TZ hydrogel exhibits potent antibacterial action and accelerates tissue repair in vivo.

Multidrug-resistant bacterial infections and chronic wounds pose significant global health challenges, often leading to prolonged suffering and high mortality rates. Current treatments frequently struggle with efficacy against resistant strains and lack comprehensive tissue regenerative properties. Supramolecular peptide hydrogels offer a promising avenue due to their dynamic, injectable nature and biocompatibility, making them ideal for localized drug delivery and tissue engineering. This research addresses the critical need for multifunctional biomaterials that can simultaneously combat infection and promote wound healing, leveraging the unique self-assembly properties of G-quartet structures and dynamic covalent chemistry.

Researchers engineered a nucleic acid-inspired constitutional dynamic hydrogel, G4TZ, through the self-assembly of guanosine, a phenylboronic acid, and a thiazole peptide. This assembly involved dynamic covalent linkages (boronate ester and imine bonds) and supramolecular interactions (π-π stacking, K+-induced G-quartet formation). The resulting transparent, injectable hydrogel was characterized for its shear-thinning and pH-responsive behavior. Its antibacterial efficacy was evaluated against multidrug-resistant Streptococcus pneumoniae in vitro, assessing reactive oxygen species generation, membrane disruption, DNA fragmentation, and biofilm inhibition. Cytocompatibility was also assessed. Furthermore, the hydrogel's capacity to accelerate re-epithelialization and promote wound healing was investigated both in vitro and in an in vivo model.

The G4TZ hydrogel demonstrated potent antibacterial activity against multidrug-resistant Streptococcus pneumoniae. This action was attributed to multiple mechanisms, including the generation of reactive oxygen species, significant membrane disruption, and DNA fragmentation, effectively inhibiting bacterial growth. Furthermore, G4TZ proved highly effective at biofilm inhibition, a critical factor in combating persistent infections. The hydrogel maintained excellent cytocompatibility, suggesting a favorable safety profile for host cells. > The G4TZ hydrogel significantly accelerated re-epithelialization and promoted comprehensive wound healing both in vitro and in an in vivo model, highlighting its dual therapeutic potential. These findings underscore the successful integration of molecular design with biological function, yielding a material with strong translational potential.