A Glucose-Responsive Hydrogel with Multifunctional Properties for Accelerated Diabetic Wound Healing

Abstract

Diabetic wounds are characterized by oxidative stress, chronic inflammation, and impaired tissue regeneration under persistent hyperglycemic conditions. Herein, we report an injectable dual-dynamic covalent hydrogel fabricated from phenylboronic-acid-functionalized oxidized sodium alginate and gallic-acid-conjugated chitosan. Crosslinked via reversible Schiff base and boronate ester bonds, the hydrogel exhibits excellent injectability, self-healing capability, and structural stability. Under hyperglycemic conditions, competitive glucose binding modulates the boronate ester equilibrium and induces glucose-responsive release of galloyl-containing species. These glucose-responsive release behaviors contribute to the antioxidant, antibacterial, and immunoregulatory activities of the hydrogel. In vitro and in vivo results demonstrate that the hydrogel promotes macrophage polarization toward the anti-inflammatory M2 phenotype, alleviates inflammatory responses, enhances angiogenesis, and accelerates skin regeneration. Collectively, the phenylboronic-acid-functionalized oxidized sodium alginate and gallic-acid-conjugated chitosan hydrogel represents a multifunctional glucose-responsive biomaterial with considerable potential for diabetic wound therapy.