In vitro studies to show sequestration of matrix metalloproteinases by silver-containing wound care products.

Excess or "uncontrolled" proteinase activity in the wound bed has been implicated as one factor that may delay or compromise wound healing. One proteinase group--matrix metalloproteinases--includes collagenases, elastase, and gelatinases and can be endogenous (cell) or exogenous (bacterial) in origin. A study was conducted to assess the ability of five silver-containing wound care products to reduce a known matrix metalloproteinase supernatant concentration in vitro. Four silver-containing wound dressings (a carboxy-methyl cellulose, a nanocrystalline, a hydro-alginate, and a collagen/oxidized regenerated cellulose composite dressing), along with a 0.5% aqueous silver nitrate [w/v] solution and controls for matrix metalloproteinase-2 and matrix metalloproteinase-9 sourced from ex vivo dermal tissue and blood monocytes, respectively, were used. Extracts were separated and purified using gelatine-Sepharose column chromatography and dialysis and polyacrylamide gel electrophoretic zymography was used to analyze specific matrix metalloproteinase activity. All dressings and the solution were shown to sequester both matrix metalloproteinases. The silver-containing carboxy-methyl cellulose dressing showed significantly greater sequestration for matrix metalloproteinase-2 at 6 and 24 hours (P< 0.001) compared to the other treatments. For matrix metalloproteinase-9, both the carboxy-methyl cellulose dressing and the oxidized regenerated cellulose dressing achieved significant sequestration when compared to the other treatments at 24 hours (P <0.001), which was maintained to 48 hours (P < 0.001). Results from this study show that silver-containing dressings are effective in sequestering matrix metalloproteinase-2 and -9 and that this can be achieved without a sacrificial protein (eg, collagen). Although the varying ability of wound dressings to sequester matrix metalloproteinases has been shown in vitro, further in vivo evidence is required to confirm these findings.

Silver deposition and tissue staining associated with wound dressings containing silver.

Argyria is the general term used to denote a clinical condition in which excessive administration and deposition of silver causes a permanent irreversible gray-blue discoloration of the skin or mucous membranes. The amount of discoloration usually depends on the route of silver delivery (ie, oral or topical administration) along with the body's ability to absorb and excrete the administered silver compound. Argyria is accepted as a rare dermatosis but once silver particles are deposited, they remain immobile and may accumulate during the aging process. Topical application of silver salts (eg, silver nitrate solution) may lead to transient skin staining. To investigate their potential to cause skin staining, two silver-containing dressings (Hydrofiber and nanocrystalline) were applied to human skin samples taken from electively amputated lower limbs. The potential for skin discoloration was assayed using atomic absorption spectroscopy. When the dressings were hydrated with water, a significantly higher amount of silver was released from the nanocrystalline dressing compared to the Hydrofiber dressing (P <0.005), which resulted in approximately 30 times more silver deposition. In contrast, when saline was used as the hydration medium, the release rates were low for both dressings and not significantly different (silver deposition was minimal). Controlling the amount of silver released from silver-containing dressings should help reduce excessive deposition of silver into wound tissue and minimize skin staining.

Wound pathophysiology, infection and therapeutic options.

Wound healing is a complex and highly regulated process that can be compromised by both endogenous factors (pathophysiological) and exogenous factors (micro-organisms). Microbial colonisation of both acute and chronic wounds is inevitable, and in most situations endogenous bacteria predominate, many of which are potentially pathogenic in the wound environment. The risk of wound infection increases as local conditions favour bacterial growth rather than host defence. Consequently a primary objective in wound management is to redress the host-bacterial balance, and this is most effectively achieved by ensuring that the wound is cleared of devitalised tissue and foreign bodies, the bacterial load and inflammation are controlled, and that adequate tissue perfusion is maintained. Although surgical debridement is the most rapid and effective technique for removing devitalised tissue, topical enzymes, moisture-retentive dressings, biosurgical therapy and vacuum therapy have been used as alternative approaches to wound cleansing and preparation. Topical antimicrobial agents continue to be used widely for preventing wound infection and current interest is focused on alternatives to antibiotics, such as antimicrobial moisture-retentive dressings, honey, essential oils and cationic peptides. In addition to the need to control wound microflora, unregulated inflammation caused by both micro-organisms and underlying abnormal pathophysiological conditions is a major factor associated with poor healing in chronic wounds. Consequently, therapeutic strategies that target chronic inflammatory processes are critical to wound progression. The success of future therapies will be dependent on a growing understanding of the pathophysiological processes and the host-bacterial interactions that significantly influence wound healing.