Antimicrobial Peptide-Enhanced Gelatin-Modified Hyaluronic Acid Hydrogels for Chronic Wounds

Overview

This study developed hyaluronic acid-based hydrogels modified with gelatin and antimicrobial peptides (AMPs) to enhance cell adhesion and provide localized antimicrobial activity against Staphylococcus aureus. The optimized hydrogels demonstrated rapid gelation, elastic properties, and supported key wound repair cells, showing promise for diabetic foot ulcer management.

Background

Chronic wounds such as diabetic foot ulcers (DFUs) result from impaired healing mechanisms linked to chronic hyperglycemia, causing dysregulated inflammation and angiogenesis. These wounds are prone to persistent infection, particularly by bacteria like Staphylococcus aureus, complicating healing. Current treatments often lack multifunctional properties to simultaneously support tissue repair and combat infection. Hydrogels based on hyaluronic acid offer a platform for bioactive wound dressings that can be chemically modified to enhance cellular interactions and antimicrobial effects.

Data Highlights

Key Findings

• Hyaluronic acid hydrogels chemically modified with acrylate groups and crosslinked with PEG dithiol form stable, elastic gels.
• Incorporation of thiolated gelatin enhances cell adhesion and bioactivity without affecting degradation.
• 0.5% gelatin concentration optimally supports adhesion and spreading of human dermal fibroblasts and iPSC-derived endothelial cells.
• Incorporation of cysteine-terminated antimicrobial peptide PP4-3.1 confers bactericidal activity against Staphylococcus aureus.
• Hydrogels maintain consistent molecular diffusion and swelling behavior across formulations.
• These multifunctional hydrogels provide structural support, enhanced bioactivity, and localized antimicrobial effects, making them promising for diabetic foot ulcer treatment.

Clinical Implications

The developed gelatin-modified hyaluronic acid hydrogels with incorporated antimicrobial peptides offer a multifunctional dressing that supports cellular adhesion critical for wound repair while providing localized antimicrobial activity to reduce infection risk. This approach could improve healing outcomes in chronic wounds such as diabetic foot ulcers by addressing both tissue regeneration and bacterial colonization simultaneously. Further preclinical evaluation is warranted to confirm efficacy and safety in vivo.

Conclusion

Gelatin and antimicrobial peptide-functionalized hyaluronic acid hydrogels demonstrate promising properties as multifunctional wound dressings for chronic wounds. Their combined bioactivity and antimicrobial effects may accelerate healing in diabetic foot ulcers and other chronic wounds.

References

1. European Federation for the Study of Diabetes/Lily European Diabetes Research Programme et al. 2023 -- 19 Antimicrobial Peptide-Enhanced Gelatin-Modified Hyaluronic Acid Hydrogels for the Management of Chronic Wounds