Ultrafast in situ formation of antibiotic-free injectable hydrogel dressings with innate antibacterial activity and autolysis capacity for wound healing

An innovative antibiotic-free hydrogel dressing was feasibly fabricated with easy injectability, excellent biocompatibility, robust tissue adhesion and unique in-situ autolysis on demand, enabling superior broad-spectrum antibacterial efficacy and promoting MRSA-infected wound healing. • A fast and catalyst-free ternary condensation reaction was employed to form a kind of antibiotic-free OSN hydrogels. • The OSN hydrogel dressings possessed facile injectability, instant tissue adhesion, good biocompatibility, and remarkable in-situ autolysis capacity. • The crosslinking sites of isoindole rings offered innate broad-spectrum antimicrobial activity against both drug-resistance bacteria and biofilm. • In vivo biological effects validated the efficient bactericidal activity for accelerating the MRSA-infected wound healing. Antibacterial hydrogels have received extensive attention in the treatment of bacterial infections. However, significant challenges persist concerning the instantaneously robust wet adhesion and self-removability on demand facing wound healing and healthcare systems, particularly when applied in direct contacting with severe drug-resistant bacterial infections. These limitations highlight the urgent need for innovative antibiotic-free wound dressings with broad-spectrum antibacterial activity and autolysis capacity to promote cutaneous wound healing while minimizing secondary damage caused by frequent dressing changes. The aim of this study was to develop a novel antibiotic-free hydrogel dressing with robust wet adhesion, tunable self-removal properties, and broad-spectrum antibacterial efficacy. The hydrogel was designed to facilitate biofilm eradication, support wound closure, and enable non-invasive removal on demand to avoid secondary injury. A fast and catalyst-free ternary condensation reaction was employed using o -phthalaldehyde (OPA), tetra-poly (ethylene glycol) mercaptan (tetra-PEG-SH), and tetra-poly (ethylene glycol) amine (tetra-PEG-NH 2 ) polymers to form an OSN hydrogel. The gelation time, tissue adhesion, and autolytic behavior were systematically characterized. The crosslinking sites of isoindole rings provided broad-spectrum antibacterial functionality and intrinsic fluorescence observation. The wound healing performance was further evaluated using a methicillin-resistant Staphylococcus aureus ( MRSA )-infected rat wound model. The OSN hydrogel exhibited ultrafast gelation, strong tissue adhesion, and excellent stability. By adjusting the initial OPA concentration, the autolytic behavior of OSN hydrogel could be precisely controlled. In vivo results demonstrated that OSN hydrogel could effectively eradicate biofilm infections, accelerate wound healing, promote reepithelization, and enable the removal of non-invasive dressings without causing secondary damage. The OSN hydrogel represents a significant advancement in antibacterial wound dressings, featuring robust tissue adhesion, controllable in-situ autolysis, and potent antibiotic-free antibacterial effects. This remarkable antibacterial therapeutic modality not only enhances the treatment of drug-resistant infections but also simplifies clinical wound management by eliminating the need for painful dressing changes, thereby supporting improved patient compliance and healing outcomes.