Silver Oxysalts Promote Cutaneous Wound Healing Independent of Infection

Introduction

Chronic wounds often exist in a heightened state of inflammation whereby excessive inflammatory cells release reactive oxygen species which cause tissue damage. Infection amplifies this response creating additional tissue damage that supports microbial growth. Antimicrobial dressings used to combat infection are rarely assessed for their cytotoxic or adverse effects on healing which may exacerbate the hostile wound environment and prolong healing. Here we assessed the effects of silver oxysalts on healing independent of infection.

Methods

Human keratinocyte and fibroblast scratch wounds were performed with and without silver oxysalts and wound closure assessed after 24 hours. In addition, dressings containing silver oxysalts were applied to murine wounds and wounds harvested after 3 and 7 days. The effects of silver oxysalts on wound area, re-epithelialisation and inflammation (immunohistochemistry for macrophage and neutrophils) were assessed. To determine direct release of oxygen or the catalysis of hydrogen peroxide (H₂O₂), oxygen levels were measured using an oxygen probe in solutions of water or H₂O₂ after the addition of silver compounds or dressings. 

Results

Silver oxysalts had no adverse effect on fibroblast scratch wound closure, while significantly promoting closure of keratinocyte scratch wounds (>95% re-epithelialisation compared to 70% in control; P=0.04). Dressings containing silver oxysalts accelerated full-thickness murine wound healing, reducing wound area (50% reduction compared to control; P=<0.03), promoting re-epithelialisation (>80% re-epithelialisation compared to <65% in control; P=<0.05) and dampening inflammation (P=<0.03). We explored the mechanisms by which silver oxysalts promote healing; unlike silvers in other commercially available wound dressings, silver oxysalts catalyse the breakdown of hydrogen peroxide to water and oxygen and directly released oxygen when exposed to water.

Conclusion

These data provide the first indication that silver oxysalts promote multiple aspects of healing in vivo independent of infection and may regulate oxidative stress within a wound through catalysis of H₂O₂.