Development of a bioactive hyaluronic acid hydrogel functionalised with antimicrobial peptides for the treatment of chronic wounds.

Abstract

Chronic wounds present significant clinical challenges due to delayed healing and high infection risk. This study presents the development and characterisation of acrylated hyaluronic acid (AcHyA) hydrogels functionalised with gelatin (G) and the antimicrobial peptide (AMP) PP4-3.1 to enhance cellular responses while providing antimicrobial activity. AcHyA-G and AcHyA-AMP hydrogels were formed <i>via</i> thiol-acrylate crosslinking, enabling <i>in situ</i> AcHyA hydrogel formation with stable mechanical properties across varying gelatin concentrations. Biophysical characterisation of AcHyA-G hydrogels showed rapid gelation, elastic behaviour, uniform mesh size, and consistent molecular diffusion across all formulations. Moreover, the presence of gelatin enhanced stability without affecting the hydrogel's degradation kinetics. AcHyA-G hydrogels supported the adhesion and spreading of key cell types involved in wound repair (dermal fibroblasts and endothelial cells), with 0.5% gelatin identified as the optimal effective concentration. Furthermore, the conjugation of the AMP conferred bactericidal activity against <i>Staphylococcus aureus</i> and <i>Escherichia coli</i>, two of the most prevalent bacterial species found in chronically infected wounds. These results highlight the dual function of AcHyA-AMP hydrogels in promoting cellular responses and antimicrobial activity, offering a promising strategy for chronic wound treatment. Further <i>in vivo</i> studies are needed to evaluate their efficacy, including in diabetic foot ulcers.