Caffeic acid and adenine modified chitosan dual-network hydrogel with antioxidant and pro-proliferative properties
Xiongying Liu1, Yufeng Wang2, Wenhao Zhang3
1Hubei Key Laboratory for Precision Synthesis of Small Molecule Pharmaceuticals & Ministry-of-Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Hubei University, Wuhan 430062, China.
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.
Insights
This study developed a novel chitosan hydrogel for diabetic wound healing. The advanced hydrogel effectively reduces inflammation and promotes cell growth, accelerating healing in diabetic patients.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Wound Healing
Background:
- Diabetic wounds present challenges in healing due to bacterial infections, oxidative stress, and reduced cell proliferation.
- Chitosan hydrogels show potential for wound treatment but require enhancement for diabetic applications.
Purpose of the Study:
- To synthesize a multifunctional chitosan derivative (A-CS-C) by incorporating adenine and caffeic acid.
- To develop dual-network hydrogels using A-CS-C and POSS-PEG-CHO for enhanced diabetic wound healing.
Main Methods:
- Grafting adenine and caffeic acid onto chitosan via a two-step amidation reaction.
- Cross-linking A-CS-C with octafunctionalized polyhedral oligomeric silsesquioxane (POSS)-PEG-CHO to form dual-network hydrogels.
- Evaluating hydrogel properties including ROS scavenging, mechanical strength, injectability, self-healing, cytocompatibility, and antimicrobial activity.
Main Results:
- The hydrogel effectively scavenged reactive oxygen species (ROS), reducing oxidative stress and inflammation.
- Demonstrated excellent mechanical properties, injectability, self-healing, and cytocompatibility.
- Exhibited sustained antimicrobial activity and significantly promoted cellular proliferation and differentiation, accelerating wound healing.
Conclusions:
- The developed multifunctional hydrogel shows significant promise for managing diabetic wounds.
- Its ROS scavenging, anti-inflammatory, and cell-promoting properties address key challenges in diabetic wound healing.
- This advanced biomaterial offers a potential therapeutic strategy for improving diabetic wound treatment outcomes.
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