R32 Higher Oxidative States of Silver Effectively Disrupts Wound Biofilms In vitro and Promote Healing of Biofilm Infected Murine Wounds

Helen Thomason, PhD1, David Warde, PhD1, Christian Stephenson, BSc1 and Andrew McBain, PhD2, (1)R&D, Crawford Healthcare, Knutsford, United Kingdom, (2)Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
Introduction

Dressings containing singly ionic silver (Ag1+) are widely used to combat wound infection; however concerns remain over their effectiveness against wound biofilms. New technology can now incorporate silver oxysalts into dressings which release silver at higher oxidative states (Ag2+/Ag3+). Here we compared the effectiveness of dressings containing Ag1+ or silver oxysalts against in vitro biofilms and in a biofilm infected murine wound model.

Methods

Dressings were applied to Staphylococcus aureus and Pseudomonas aeruginosa biofilms grown on membranes for 24 hours. At 24 hour intervals biofilms were disrupted and remaining viable biofilm bacteria quantified by standard plate counts. Visualisation of the effects of the dressings on 3 day mature P. aeruginosa biofilms cultured in a porcine skin ex vivo model was performed using a viability dye and scanning electron microscopy (SEM). Finally, the effects of the silver dressings on P. aeruginosa biofilm infected murine excisional wounds were assessed in vivo.

Results

Log reductions indicate that the silver oxysalt dressing significantly reduced S. aureus and P. aeruginosa biofilms over 8 days with re-inoculation after 5 days (>5 log), whereas Ag1+ dressing had little effect on biofilm viability (< 1 log). Viability staining and SEM showed a greater effect against mature P. aeruginosa biofilms with silver oxysalts dressings compared to Ag1+ dressings. Treatment of P. aeruginosa biofilm infected murine wounds with silver oxysalt dressings resulted in a 4 log reduction within 3 days. Silver oxysalt treated wounds were 30% smaller than control or Ag1+ treated wounds and exhibited greater re-epithelialisation. Finally, significantly fewer inflammatory cells infiltrated wounds treated with silver oxysalts compared to control and Ag1+ treated wounds.

Conclusion

The potent nature of silver oxysalts effectively disrupts mature biofilms and promotes healing of murine wounds, reducing wound size, increasing re-epithelialisation and dampening inflammation.