Metal polyphenol double-network hydrogels based on chitosan/hyaluronic acid loaded with rosmarinic acid promote the healing and repair of infected wounds

Nov 1, 2025International journal of biological macromolecules

Metal-polyphenol hydrogels with natural acids on chitosan and hyaluronic acid help heal infected wounds

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Regenerative Health on OpenScience ↗PubMed ↗DOI ↗

Abstract

The dual-network hydrogel achieved approximately 95% wound healing within 14 days.

The hydrogel exhibits rapid self-healing capabilities, completing this process within 5 minutes.
Antibacterial efficacy is demonstrated, with over 90% inhibition of both Staphylococcus aureus and Escherichia coli within 12 hours.
The hydrogel effectively scavenged more than 80% of reactive oxygen species in vitro.
It promotes M2-type macrophage polarization, which is associated with tissue repair and reduced pro-inflammatory cytokine levels.
Histological analysis shows reduced inflammation, increased collagen alignment, and enhanced epidermal regeneration.

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Bacterial infection and chronic inflammation after skin injury impede wound healing. Conventional treatments are limited by issues such as drug resistance and insufficient penetration, prompting the need for novel multifunctional dressings. In this study, a dual-network hydrogel (CS-RA/Zn-OHA) that incorporates chitosan grafted with rosmarinic acid (CS-RA), oxidized hyaluronic acid (OHA), and zinc ions (Zn) was developed. The hydrogel exhibits good mechanical properties, rapid self-healing within 5 min, and injectability because of dynamic Schiff base reactions and metal-polyphenol coordination. It shows potent, broad-spectrum antibacterial efficacy, achieving >90.00 % inhibition against both Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) within 12 h. Additionally, this hydrogel facilitated the sustained release of rosmarinic acid and scavenged reactive oxygen species (ROS); in vitro, the hydrogel effectively scavenged over 80 % of ROS. It also modulated the immune microenvironment by promoting polarization toward M2-type macrophages with tissue repair functions and significantly reducing levels of pro-inflammatory cytokines, thereby exerting a more robust regulatory effect on inflammation. In vivo experiments demonstrate that treatment significantly accelerated closure, achieving ∼95 % wound healing within 14 days. Histological analysis confirms that inflammation is reduced, collagen alignment is increased, and epidermal regeneration is enhanced. Overall, the CS-RA/Zn-OHA hydrogel demonstrates considerable potential in the treatment of bacterium-infected wounds owing to its robust antibacterial, anti-inflammatory, and antioxidant properties, thereby offering a highly effective and safe therapeutic strategy for wound management. 2+ 2+ 2+

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Metal polyphenol double-network hydrogels based on chitosan/hyaluronic acid loaded with rosmarinic acid promote the healing and repair of infected wounds

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