Moist Wound Healing
       Moist wound healing has been around for about 40 years, initially fostered by findings that moisture-occlusive dressings (that maintain a moist environment) promoted healing when compared to nonocclusive gauze-style wound coverings. The maintenance of moisture in the wound was thought to enhance cellular functions that assist healing and decrease scarring. Wound care products that possess occlusive characteristics have evolved to improve moisture management. Although a moist environment allows cells of healing to optimally undergo proliferation, cellular communication, and matrix protein deposition, this environment is also conducive to microbial proliferation. Rather than ending up with healthy granulating wounds, the result may be sloughing non-healing wounds as a consequence of the development of resident bioburden.
       More than 90% of all wounds have a bioburden. Moreover, greater than 50% of chronic wounds will progress from having organisms present to an overt infection. The premise that bioburden is undesirable has not been universally shared by wound care providers. Although it is generally agreed that overt infection represents a clinical problem, some clinicians have thought that low bioburden is inconsequential or may even be beneficial to wound healing. This reasoning has been based on the perception that a resident bioburden may compete with pathogens or that they may stimulate a level of inflammation that could increase beneficial activity such as profusion of the tissues. It is likely that both of these concepts are overly simplistic. The wound is an abnormal state and the presence of micro-organisms within any area of the wound should not be considered desirable. The clinical reality is that most chronic wounds have micro-organisms in them, but wound bioburden traditionally is only assessed when clinical signs and symptoms of infection are present. This practice has largely caused clinicians to overlook the significance of sub-infectious levels of bacteria.

Assessing the Wound Environment
       The wound environment can be divided into three large zones. The overlying zone is used to describe the nonviable area over the wound bed where exudate accumulates. In moist wound healing, an accumulation of fluid and necrotic nonviable debris ("wound muck" in the vernacular) is found between the dressing and the wound bed. The granulation layer or wound bed is a relatively thin environment, perhaps at times only a few cells thick. The third zone is the underlying healthy tissue under the wound. One of two methods is generally used to detect microbial bioburden: quantitative punch biopsy or the semi-quantitative swab method of sample collection followed by in vitro culture in the laboratory. Both methods prescribe cleaning the wound bed before sample collection. As a result, these tests evaluate the wound bed and underlying tissues for micro-organisms. The presence of significant levels of micro-organisms in these environments is generally interpreted as an infection. On a numerical basis, in a punch biopsy, greater than 105 organisms per gram is considered to be consistent with an infection. In a semi-quantitative swab test, moderate-to-heavy growth is generally the indicator. Either result is commonly translated into the need for systemic antibiotics. Although generally instructive, these tests do not address the bioburden over the wound bed, leading to the supposition that organisms in that zone are irrelevant to the wound healing process.
       Researchers and clinicians are gaining a greater appreciation of the role that even low levels of microbial bioburden contribute to the chronic state of wounds. The presence of microorganisms may significantly alter physiological functions that have a direct influence on the proliferative and matrix deposition processes necessary to achieve wound closure. This may occur through influences on 1) the recruitment and migration of white cells and fibroblasts into the wound, 2) the tissue oxygen tension, 3) enzyme degradation of matrix, 4) and wound pH. In addition, exotoxins produced by micro-organisms may act on the delicate cell populations of the proliferative zone to arrest cellular growth and matrix protein deposition.
       Chemotaxis and cellular recruitment. Recruitment broadly addresses local tissue signals that cause specific cells to migrate and accumulate in the wound. In a normal uncomplicated acute wound, the chronological sequence reveals an influx of polymorphonuclear leukocytes soon after hemostasis to marshall defenses, should a significant number of microbes accumulate. Macrophages accumulate more slowly to remove necrotic debris and produce signals to recruit fibroblasts into the zone and stimulate metabolic functions such as proliferation and matrix protein deposition. Although they can kill bacteria, this is primarily a function of neutrophils. When the wound base has been repaired and neodermis has formed, keratinocytes move in and cover the entire area to effect closure or healing.
       In chronic wounds, this scenario may be modified by the presence of bacteria. The sequence of events typically is halted early in that cascade, resulting in the perpetual influx of polymorphonuclear leukocytes, often observed as yellow fibrinous slough. These short-lived cells function for a short time and then die, liberating a powerful load of degradative enzymes into the wound environment. Several of these are metalloproteases that are erosive to matrix proteins. The accumulation of these cells is due predominately to chemotactic signals produced by bacteria. The elimination of bacteria may contribute to shifting cellular infiltration to a monocyte/macrophage-rich stage, the cellular population of which can orchestrate wound repair processes.

The Role of Silver
       Silver provides an antimicrobial action in aqueous fluids that is highly toxic for micro-organisms but has relatively low toxicity for human tissue cells. Most silver products on the wound care market utilize metallic silver as the reservoir for ionic silver - the only state of silver that has antimicrobial effect. When the metallic form is used as the reservoir, the transition occurs through oxidation to form the ionic species. A newer product uses technology that couples silver in the ionic state to another chemical to form the silver reservoir.
       The highly reactive characteristic of silver is its nemesis and its advantage. Silver works as an antimicrobial through a number of pathways. The ionic species carries a strong positive charge so it has high affinity for negatively charged groups of biological molecules. These include groups such as sulfhydryl, carboxyl, phosphates, and other groups commonly found on macromolecular structures distributed throughout microbial cells. The binding reaction alters the molecular structure of the macromolecule, rendering it worthless to the cell. This attack on multiple sites within a cell simultaneously inactivates many functions such as cell wall synthesis, membrane transport, nucleic acids such as RNA and DNA synthesis and translation, and protein folding and function. Without these functions, the bacterium is either inhibited from growth or, more commonly, dies. The development of antimicrobial resistance to silver would be extremely rare because an organism would have to undergo simultaneous mutation in every function affected by silver to escape its influence.
       Because silver affects so many different functions of microbial cells, it is non-selective, resulting in antimicrobial activity against a broad spectrum of micro-organisms including bacteria, fungi, and yeasts. Silver is also favored because it is extremely active in small quantities against micro-organisms. With certain bacteria, as little as 0.1 part per billion may have an antimicrobial effect. However, using silver for bioburden control in wounds is not problem-free. Historically, the active form is rapidly inactivated in the wound environment, necessitating repeated applications to ensure continued effectiveness. It also has a reputation for staining tissues and equipment. These properties are stability issues that are exacerbated when silver is in the presence of moisture.

Absorbency and Silver Technology
       A new product - SilvaSorb(TM) - has overcome the difficulties of placing ionic silver in a sophisticated moist wound dressing matrix for antimicrobial activity. This stabilized silver technology overcomes the inherent stability issues of the silver to inhibit its reaction to light, prevent staining of tissues, and allow sterilization by conventional irradiation methods. Several formats of the hydrophilic product are available, including an occlusive sheet, a perforated sheet, and a filamentous cavity fill form, all of which release ionic silver when in contact with moisture such as wound exudate. One of the keys to its performance is Microlattice(TM), a cross-linked polyacrylate scaffolding that provides the substance of the product's matrix. The cross-linked matrix provides molecular sinuses within the matrix where the particulate ionic silver reservoir becomes trapped during manufacturing. Ionic silver is mobilized when it comes into contact with moisture from the wound fluid as the wound is dressed. As moisture enters the dressing, it dissolves the silver reservoir and releases ionic silver that diffuses from the matrix to act on microorganisms. The product's sensitivity to light or sterilization energy and its inclination to stain is controlled by minimizing the amount of ionic silver present in the product until it is applied to the patient.
       Through a process called silver cascade, moisture from the wound or skin enters the dressing. As it dissolves some of the complex, it liberates free ionic silver that diffuses in the moisture phase, migrating to establish a level sufficient for antimicrobial action in the wound. Because this process is governed by equilibrium dynamics, it results in the maintenance of between 1 and 2 parts per million (ppm) ionic silver in the moisture phase. The equilibrium is maintained at this level by the formation of the weakly soluble silver chloride salt that forms through a reaction with chloride ions in the wound exudate, ensuring the delivery of silver to lethal target sites on bacteria. This also prevents the staining that occurs when a large amount of silver is rapidly dumped into the wound environment. It is desirable to maintain about a 1 ppm residual silver ion, a quantity more than adequate to provide an antimicrobial effect for medically relevant micro-organisms.

Technical Properties
       Absorbency. The product is extremely hydrophilic, absorbing approximately six times its weight in moisture. It is also highly elastic and flexible, allowing it to conform to the skin and wound sites with negligible adherence to the wound when removed. The material is occlusive to micro-organisms unless it is perforated during manufacturing or upon application. Perforations or cutting it into a stranded format can be used to customize its moisture management properties to suit the conditions of the wound. For example, perforations or cutting into filaments increase the surface area for absorption and channels for exudate to flow to a secondary dressing while simultaneously maintaining a moisture reservoir in the contact area to prevent desiccation. Its moisture vapor transmission rate is approximately 2,200 g/m2/24 h, allowing control of moisture loss. For example, in a wound such as a skin tear, the product can be applied and occluded with a thin film dressing to decrease moisture vapor transmission. However, in a weepy, highly exuding wound, moisture vapor transmission might be encouraged with a gauze secondary dressing secured with a non-woven adhesive dressing or wrap. A curious dichotomy with this particular wound dressing is that it can both absorb and donate moisture as might be useful on cross-hatched eschar that is relatively dry. This occurs because the product carries a 22% to 25% moisture loading that can be utilized to initiate and support autolytic debridement.
       Antimicrobial activity. The product has been tested against about 90 strains and clinical isolates, including Gram-positive and Gram-negative bacteria, as well as strains of yeasts and fungi. It can be effective for 7 days or more, but clinicians are cautioned to change dressings when moisture absorption capacity has been reached, not when the dressing is out of silver.
       Staining. Staining interferes with interpretation of the wound. This product was developed to provide and maintain sufficient silver in the wound fluid to be an effective antimicrobial without causing staining.
       Sensitivity. Some heavy metals such nickel and lead have a reputation for causing sensitivities in certain individuals. Silver is a heavy metal that avidly binds to protein, yet reports of sensitization are extremely rare.

Conclusion
       The nature of the cellular exudate that accumulates in a wound may influence wound healing. Wound management tools that help control the nature of the exudate - specifically, eliminating micro-organisms from the wound bed that cause erosive damage - should include silver products. Silver is non-toxic, active, and readily available. New tools allow clinicians to control antimicrobial activity and manage moisture.

Questions and Answers
QUESTION: Have you looked into the application for non-colonized clean wounds such as donor sites?
BRUCE GIBBINS: A donor site study is currently being conducted. The benefits of a material like this go beyond the control of bioburden in the donor site to include patient comfort.
QUESTION: When using silver nitrate, staining is almost a comfort because the clinician can see the product is reacting. Why does this product not stain, and what is the importance of staining versus the problem of not being able to evaluate the wound base?
BRUCE GIBBINS: Ionic silver is colorless. When it has reacted with something, it is inactivated and free to become reduced to form a black or darkening color. When discoloration and staining is visible, it is inactivated. This occurs with silver nitrate.
QUESTION: Does it matter whether the wound is washed with saline or water? Some of the products recommend using water.
BRUCE GIBBINS: Washing with a little water or saline will not upset natural body salinity. Body salinity regulates the free silver ion concentration within the wound regardless of the product. Therefore, whether the wound is washed with water or saline isn't a cause for concern.
QUESTION: When using the tendril form of the product for filling cavities and 24 or 48 hours later when the dressing is changed, is it safe to just rinse that dressing off and continue to reuse it? How do you know when enough moisture from the wound has consumed all the silver? And considering the zone of inhibition, how do you know how much dressing to put in the wound to maximize your reaction but not to overuse the product?
BRUCE GIBBINS: You don't want to necessarily try to get more uses out of that dressing to get more silver out of it. You have used up the benefit of the moisture control and you also have taken the much of the silver out of the dressing. With a cavity application, fill about 60% of the free space by loosely layering the material. As it takes up moisture in that environment, it will swell slightly to conform to the wound. Typically in a heavily draining wound, absorption capacity and silver activity will be reached in 2 to 3 days. By contrast, a skin tear, a low exudative wound, might allow 11 to 12 days of dressing wear. When the dressing falls off a skin tear, the wound is typically healed. Therefore, when the moisture side of the dressing is exhausted, the silver side is also close to exhausted.
QUESTION: What is nanocrystalline silver; how is that different?
BRUCE GIBBINS: Nanocrystalline silver technology is a design that releases a great deal of silver. The benefit of nanocrystalline is that it is an extremely small particle, typically around 20 to 70 nanometers in size. The value of a particle is that it has a large surface area-to-volume ratio, so the volume of silver in the crystal is largely represented on the outside, making it more susceptible to oxidation. Nanocrystalline silver goes through a silver-to-silver oxide transition, so the silver oxide is soluble in water.