Injectable exosome-loaded quaternized chitosan/oxidized sodium alginate hydrogel with self-healing, bioadhesive, and antibacterial properties for treating combined radiation-wound injury

The management of combined radiation-wound injury (CRWI) is a major clinical challenge owing to the delayed and prolonged wound-healing process. Moreover, the mechanisms underlying the healing of CRWI are complex, and chronic wounds can increase vulnerability to multidrug-resistant bacterial infections, vascular disease, and other adverse conditions. Although exosomes from iPSC-derived mesenchymal stem cells (iMSCs) can promote injury repair, the feasibility of encapsulating them within polysaccharide-based hydrogels to treat CRWI remains to be explored. Here, iMSC-derived exosomes were encapsulated within an injectable hydrogel (HACC/OSA) consisting of quaternized chitosan (HACC) and oxidized sodium alginate (OSA). The HACC/OSA hydrogel exhibited good self-healing properties, excellent injectability, and good biocompatibility. In mouse models of CRWI, the HACC/OSA hydrogel could form a protective barrier covering the wound. Due to the presence of quaternary ammonium salts, the hydrogel could provide long-term antimicrobial protection to the wound, which was favorable for wound healing. In addition, the hydrogel could also promote CRWI repair by stabilizing exosome release. The exosome-loaded hydrogel (HACC/OSA@Exos) significantly inhibited bacterial growth and promoted the repair of CRWI, as indicated by enhanced wound healing efficiency, rapid re-epithelialization, favorable collagen deposition, and abundant angiogenesis at the wound site. Together, the in vivo and in vitro results indicated that the exosome-loaded polysaccharide-based hydrogel (HACC/OSA@Exos) can promote the healing of CRWI and potentially serve as a valuable clinical agent for CRWI management.