A pH-responsive hydrogel based on polysaccharides incorporated with honeysuckle-derived exosome-like nanovesicles for...

The management of infected wounds is a major clinical challenge because the healing process is often obstructed by several related pathological factors, such as drug-resistant microbial infections, persistent inflammatory responses, oxidative stress, and impaired angiogenesis. In this study, we developed an injectable hydrogel (CTOHo) designed using honeysuckle-derived exosome-like nanovesicles (HoNVs) incorporated into a dynamic network created from carboxymethyl chitosan (CMCS), tannic acid (TA), and oxidised sodium alginate (OSA). HoNVs were isolated from fresh honeysuckle and characterised. The CTO-Ho hydrogel is synthesised through a dynamic network structure composed of CMCS, OSA and TA and loaded with HoNVs. Systematic characterisation and evaluation of the physicochemical properties of the CTO-Ho hydrogel were performed. The antibacterial activity against S. aureus, E. coli and MRSA; macrophage polarisation; ROS scavenging; HUVEC migration/tube formation; and full-thickness S. aureus-infected rat wounds were evaluated over 14 days. The resulting hydrogel was found to possess high gelation kinetics, good injectability with accurate adherence to the wound topography, and the pH-sensitive release of HoNVs under acidic conditions. Bioactive phytochemicals, such as flavonoids, phenolic acids, and alkaloids, are enriched in HoNVs. The synergistic interaction between HoNVs and TA endows CTO-Ho with strong biocompatibility, promotes angiogenesis, suppresses inflammation, exhibits antimicrobial activity, and scavenges reactive oxygen species, greatly increasing the regeneration of infected tissues. This plant exosome-functionalised carbohydrate-based hydrogel system offers a holistic and clinically viable approach for the targeted treatment of complex infected wounds.