Geranium essential oil downregulates virulence genes and mitigates MRSA wound infections through a multifunctional hydrogel

This study presents the development of a multifunctional hydrogel system that incorporates a natural therapeutic agent to promote wound healing and combat bacterial infections. A geranium essential oil (GEO)-loaded carboxymethyl chitosan-pullulan (CMCS-PLN-GEO) hydrogel was formulated for the treatment of MRSA-infected wounds. GEO exhibited potent antibiofilm and antivirulence properties by significantly downregulating key virulence-associated genes such as sarA, agrA, icaA, icaD, and clfA, indicating its potential as an effective therapeutic agent against MRSA. Integration of GEO into the CMCS-PLN hydrogel matrix enhanced its mechanical strength, reduced pore size, and enabled sustained GEO release. In a zebrafish wound model, the CMCS-PLN-GEO hydrogel markedly accelerated wound closure and suppressed MRSA colonization. Furthermore, it demonstrated strong anti-inflammatory activity through the downregulation of interleukin-1β (IL-1β), while promoting tissue regeneration via upregulation of transforming growth factor-β (TGF-β) and inhibition of matrix metalloproteinases MMP-9 and MMP-13. The synergistic integration of GEO with the CMCS-PLN polymer matrix offers dual antibacterial and anti-inflammatory effects, presenting a holistic therapeutic approach for the effective management of MRSA-infected wounds. The present study suggests that GEO-loaded hydrogel is a promising biomaterial for treating MRSA-infected wounds, potentially advancing toward clinical applications.