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Caffeic acid and adenine modified chitosan dual-network hydrogel with antioxidant and pro-proliferative properties for diabetic wound healing.

Xiongying Liu,Yufeng Wang,Wenhao Zhang,Jiaxi Jiang,Yingjie He,Xinyue Huang,Chao Ma,Xiaofan Yang,Yu Kang,Cuifen Lu

Published 2025 in Carbohydrate Polymers

ABSTRACT

Chitosan-based hydrogels hold significant promise as therapeutic dressings for wound treatment. However, their performance in diabetic wound healing remains limited. Diabetic wounds are difficult to heal due to bacterial infections, excessive reactive oxygen species (ROS) production, and reduced cellular proliferation caused by diabetes-related complications, resulting in prolonged and severe inflammation. To address these challenges, a multifunctional chitosan derivative (A-CS-C) was synthesized by grafting proliferation-promoting adenine and antioxidant caffeic acid onto chitosan through two-step amidation reaction under precisely controlled substitution conditions. Subsequently, the dual-network hydrogels were prepared by cross-linking the multifunctional chitosan derivative A-CS-C with octafunctionalized polyhedral oligomeric silsesquioxane (POSS) of benzaldehyde-terminated polyethylene glycol (POSS-PEG-CHO). The developed hydrogel effectively scavenged excess ROS during early inflammation, reducing oxidative stress and mitigating excessive inflammatory responses at the wound site. It demonstrated excellent mechanical properties, injectability, self-healing capability, and cytocompatibility. Moreover, the hydrogel exhibited sustained antimicrobial activity, significantly promoting cellular proliferation and differentiation, which accelerated wound healing. Owing to its excellent biological function and physicochemical properties, this multifunctional hydrogel presents a promising therapeutic approach for diabetic wound management.

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