Immunomodulatory hydrogel reprograms IL-17/NF-κB signaling to drive regeneration in diabetic wounds

Diabetic wound repair remains a formidable clinical challenge due to impaired healing and heightened infection risks associated with conventional sutures. To address these limitations, this study introduces a novel injectable, self-healing, and antibacterial polysaccharide hydrogel (PGHAA), synthesized from borated peach gum and oxime-modified hyaluronic acid. By leveraging dynamic boronic ester bonds and metal coordination, PGHAA demonstrates enhanced tissue adhesion, self-healing capabilities, and antibacterial activity with immunomodulatory capacity to reprogram chronic wounds into a regenerative state. The incorporation of arginine as a cross-linking agent further improves both biocompatibility and functional performance. In vitro and in vivo evaluations indicate that PGHAA facilitates rapid hemostasis, robust tissue adhesion, and macrophage polarization toward a pro-regenerative phenotype, resulting in accelerated diabetic wound healing. Using an in vivo study with chronic diabetic skin we demonstrated that PGHAA induced wound healing via modulation of IL-17/NF-κB signaling—a pathway repurposed from its classical inflammatory role to drive tissue regeneration. This work redefines diabetic wound therapy by introducing a first-in-class hydrogel that leverages immune modulation for tissue repair, offering a transformative solution for regenerative medicine.