Copper Oxide Impregnated Wound Dressing: Biocidal and Safety Studies
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Copper ions, however, cause non-specific simultaneous damage to microorganisms via: A) denaturation of nucleic acids by binding to and/or disordering helical structures and/or by cross-linking between and within nucleic acid strands36,37; B) alteration of proteins and inhibition of their biological assembly and activity38,39; C) plasma membrane permeabilization35,40,41; and D) membrane lipid peroxidation.41–43 Some microorganisms have developed several mechanisms to tolerate excess concentrations of metal, including copper,40 and are thus less sensitive to copper than others.2 However, exposure of microorganisms including viruses, gram-positive and gram-negative bacteria, and fungi to high concentrations of copper ions, like those released by the wound dressings, results in simultaneous damage to many cellular components.1 Accordingly, the present study did not find any reduction in sensitivity by bacteria consecutively exposed to fabrics containing only 1% (w/w) copper oxide. It is not surprising that copper, despite its presence throughout human history and its historical use as an antimicrobial agent, remains a broad-spectrum biocidal/antimicrobial compound to which microbes have not been able to develop resistance.1
To allow the wound dressing to exert its potent biocidal properties not only against bacteria found in the dressing itself, but also against bacteria present within the wound, the copper oxide wound dressing was designed to be flexible with high conformability so as to easily adhere to all wound surfaces. This reduces to a minimum the formation of voids (dead spaces), where bacteria may flourish, thereby impeding successful wound healing.44 The close proximity of the copper oxide containing dressings and the wound surface allows for more efficacious copper ion release from the dressings into the dressing/wound interface. Additionally, the high absorbency and flexibility of the copper oxide dressing assures better sequestration of the bacteria by absorbing the exudates into the internal layers and reducing the bioburden in the wound. Sequestration of bacteria has been shown to be an important feature of wound dressings.45
Another obvious concern when using antimicrobial agents in wound dressings is their safety since antimicrobial agents exposed to open wounds can be systemically absorbed. For example, the concentration of silver, which is widely used as an antimicrobial agent in wound dressings due to its biocidal properties, can increase by more than 130 fold in plasma and urine of silver sulfadiazine cream-treated burn patients within 6 hours of exposure.46 Absorption can lead to toxicity and, indeed, renal toxicity from silver has been reported after topical application.47 Similarly, hepatic dysfunction was reported in patients with burns treated with silver dressings,48 although this was resolved after cessation of the silver treatment. In another recent study, accumulation of silver and delayed re-epithelialization in normal human skin when using different silver containing wound dressings has been reported.49 Furthermore, there is increased concern regarding the safety of silver use, and in particular nanosilver, in wound dressings and in medical devices in general.50 Nevertheless, the use of silver dressings is gaining popularity51 and is generally considered safe.
Copper, as opposed to silver, is an essential trace element needed for the normal function of many tissues, such as the integument, nervous and immune systems, and in general for the normal function of many metalloproteins, gene expression regulatory proteins, and many metabolic processes.11,52 Copper, unlike silver, is readily metabolized and utilized by the body when absorbed either orally or through tissues.