Injectable antibacterial tissue-adhesive hydrogel based on biocompatible o-phthalaldehyde/amine crosslinking for efficient treatment of infected wounds

Injectable antibacterial hydrogels have attracted considerable attention in wound management. However, the development of injectable hydrogels with excellent antibacterial activity , good biocompatibility , and strong tissue adhesion remains a challenge. In this study, an antibacterial tissue-adhesive hydrogel was developed based on a catalyst-free o -phthalaldehyde (OPA)/amine reaction by simply mixing OPA-terminated four-arm poly(ethylene glycol) (4aPEG-OPA) and ε-poly- l -lysine (ε-PLL) solutions. The hydrogel showed tunable gelation time, storage moduli , and degradation rate depending on the polymer concentration and 4aPEG-OPA/ε-PLL mass ratio. The hydrogel exhibited nearly 100% bacterial inhibition rates in-vitro against Gram-negative E. coli and Gram-positive S. aureus , while maintaining good biocompatibility. The hydrogel matched well in shape and tightly adhered to the tissue after in-situ formation at the wound sites. Following the treatment of rat models of full-thickness skin incisions and round wounds, the hydrogel effectively closed the wounds and promoted wound healing. Moreover, after administering to S. aureus infected full-thickness skin wounds, the hydrogel exhibited remarkable efficacy in inhibiting wound infection with a bacterial inhibition rate over 99.94%, achieving a significantly accelerated wound healing compared with the commercially available Prontosan® gel. Therefore, the hydrogel exhibits great potential as a wound dressing for infection prevention and promotion of healing.