Sulfonated chitosan combined with exosomes synergistically promotes vascularization and macrophage M2 polarization to promote wound healing

Effective wound management remains a critical clinical challenge, with its inherent complexity posing a substantial burden on patient quality of life. Inadequate treatment can result in severe complications, including tissue infection, necrosis, and the loss of both localized and systemic physiological functions. Consequently, over the past decade, researchers have actively explored new approaches to accelerate wound healing. Here, we report the design of a multifunctional composite hydrogel dressing that simultaneously suppresses inflammation and promotes tissue regeneration by enhancing angiogenesis and modulating macrophage polarization. The hydrogel is crosslinked from amino-functionalized hyaluronic acid, aldehyde-functionalized dextran, and sulfonated chitosan, exhibiting excellent mechanical properties and biocompatibility, rendering it a highly suitable platform for controlled and sustained therapeutic delivery. Specifically, the hydrogel is engineered to incorporate exosomes derived from human umbilical cord mesenchymal stem cells (HUCMSC-Exo), which encapsulate hexaminolevulinate hydrochloride (HAL). HAL@Exo regulates cell communication, enhances cellular migration and proliferation, facilitates collagen matrix deposition and angiogenesis, and produces anti-inflammatory bioactive substances through biometabolic processes, thereby alleviating the extent of local inflammatory response. In a rat full-thickness skin wound model, the hydrogel demonstrated a pronounced therapeutic effect, significantly accelerating the wound healing process.