Microenvironment-responsive smart hydrogels with antibacterial activity and immune regulation for accelerating chronic wound healing

Current therapeutic strategies for chronic refractory wounds remain challenge owing to their unfavorable wound microenvironment and poor skin regeneration ability. Thus far, a regimen for effective chronic refractory wounds management involves bacterial elimination, alleviation of oxidative stress, inhibition of inflammatory response, and promotion of angiogenesis. In this work, an injectable glycopeptide hydrogel based on phenylboronic acid-grafted ϵ-polylysine (EPBA) and poly (vinyl alcohol) (PVA) with pH/reactive oxygen species (ROS) dual-responsive properties was prepared, which exerted intrinsic antibacterial and antioxidant properties. ROS-responsive micelles (MIC) loaded with herb-derived Astragaloside IV (AST) are introduced into the hydrogel before gelation. Attributed to the acidic condition and oxidative stress microenvironment of wound bed, the hydrogel gradually disintegrates, and the released EPBA could help to eliminate bacterial. Meanwhile, the subsequential release of AST could help to achieve anti-oxidation, anti-inflammatory, proangiogenic effects, and regulation of macrophage polarization to accelerate chronic wound healing. In addition, the wound repair mechanism of composite hydrogel accelerating skin regeneration was assessed by RNA-sequencing, exploring a range of potential targets and pathway for further study. Collectively, this multifunctional hydrogel dressing, matching different healing stages of tissue remodeling, holds a great potential for the treatment of chronic refractory wounds.