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March 4, 2026International Journal of Nanomedicine0 citationsOpen Access

Chitosan-Hyaluronic Acid Composite Hydrogel with Slow-Release Hydrogen Sulfide and Cerium Oxide for Multifunctional Synergy to Promote Healing of Infected Wounds

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XWXing WangJiangsu UniversityKZKai ZhuUniversity of British ColumbiaWLWanxin Liu

Key Points

  • The research aims to develop a hydrogel dressing that promotes healing in chronic infected wounds through the sustained release of hydrogen sulfide.
  • Sodium hydrosulfide-loaded cerium oxide was synthesized and incorporated into a chitosan-hyaluronic acid hydrogel.
  • The hydrogel's properties were characterized, and its biological functions were evaluated using various assays.
  • A rat model infected with MRSA was used to assess the efficacy of the dressing on wound healing.
  • The dressing demonstrated a 98.1% wound closure rate by day 14 in the MRSA-infected rat model.
  • It showed sustained hydrogen sulfide release, improved tissue healing, and enhanced angiogenesis with reduced apoptosis at the wound site.
  • Antibacterial activity was observed against Escherichia coli and MRSA, with maintenance of cell viability under oxidative stress.

Abstract

Introduction: The management of chronic infected wounds imposes a substantial economic burden on patients and significantly impairs their quality of life due to persistent wound infections and delayed healing. To address this issue, we developed a multifunctional dressing with sustained hydrogen sulfide (H 2 S) release to accelerate wound healing. Methods: Sodium hydrosulfide-loaded cerium oxide (NaSH@CeO 2 ) was synthesized via rotary evaporation and subsequently incorporated into a hydrogel dressing crosslinked with chitosan (CS) and hyaluronic acid (HA), yielding NaSH@CeO 2 /CS-HA. The composite was characterized, and H 2 S release was quantified using the methylene blue method. The biological functions of NaSH@CeO 2 /CS-HA were evaluated through CCK-8 assay, Calcein-PI staining, DCFH-DA detection, scratch assay, tube formation assay, and antibacterial tests. A methicillin-resistant Staphylococcus aureus (MRSA)-infected wound model was established in rats to assess therapeutic efficacy based on wound healing rate, hematoxylin-eosin (H&E) staining, Masson’s trichrome staining, and immunofluorescence staining. Results: NaSH@CeO 2 /CS-HA demonstrated sustained H 2 S release without cytotoxicity while effectively inhibiting Escherichia coli and MRSA. Furthermore, it reduced intracellular reactive oxygen species levels, maintained cell viability under H 2 O 2 -induced oxidative stress, promoted mouse fibroblast cells (L929 cells) migration, and enhanced tube formation in human umbilical vein endothelial cells (HUVECs). In the MRSA-infected rat wound model, the NaSH@CeO 2 /CS-HA group achieved a 98.1% wound closure rate by day 14. H&E and Masson’s staining revealed enhanced tissue healing, while immunofluorescence (CD31, Caspase-3) confirmed increased angiogenesis and reduced apoptosis at the wound site. Conclusion: The developed gel dressing (NaSH@CeO 2 /CS-HA) intelligently regulates H 2 S release, combining antioxidant, antibacterial, and wound-healing functions into one, providing a comprehensive treatment solution for chronic infectious wounds with significant clinical application potential. Keywords: wound healing, MRSA infected wound, hydrogen sulfide, cerium oxide nanoparticle, hydrogel

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Cite This Study

Wang et al. (2026) studied this question.

synapsesocial.com/papers/69a7cd5ed48f933b5eed99a9https://doi.org/10.2147/ijn.s538774
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