Silver Oxysalts Promote Cutaneous Wound Healing Independent of Infection

Abstract

Chronic wounds often exist in a heightened state of inflammation whereby excessive inflammatory cells release high levels of proteases and reactive oxygen species (ROS). While low levels of ROS play a fundamental role in the regulation of normal wound healing, their levels need to be tightly regulated to prevent a hostile wound environment resulting from excessive levels of ROS. Infection amplifies the inflammatory response, augmenting levels of ROS which creates additional tissue damage that supports microbial growth. Antimicrobial dressings are used to combat infection; however, the effects of these dressing on the wound environment and healing independent of infection are rarely assessed. Cytotoxic or adverse effects on healing may exacerbate the hostile wound environment and prolong healing. Here we assessed the effect on healing independent of infection of silver oxysalts which produce higher oxidative states of silver (Ag²⁺/Ag³⁺). Silver oxysalts had no adverse effect on fibroblast scratch wound closure whilst significantly promoting closure of keratinocyte scratch wounds (34% increase compared to control). Furthermore, dressings containing silver oxysalts accelerated healing of full-thickness incisional wounds in wild-type mice, reducing wound area, promoting re-epithelialisation and dampening inflammation. We explored the mechanisms by which silver oxysalts promote healing and found that unlike other silver dressings tested, silver oxysalt dressings catalyse the breakdown of hydrogen peroxide to water and oxygen. In addition, we found that silver oxysalts directly released oxygen when exposed to water. Collectively, these data provide the first indication that silver oxysalts promote healing independent of infection and may regulate oxidative stress within a wound through catalysis of hydrogen peroxide. This article is protected by copyright. All rights reserved.