Clinical research and general experience is accentuating the importance of minimizing the bacterial load in both chronic and acute wounds. This understanding, combined with the increasing prevalence of anti biotic-resistant bacteria in both hospital and community settings, is driving the development of new types of antimicrobial dressings. Various products tout their antimicrobial efficacy, but little is described relative to their impact on wound healing. Two new antimicrobial dressing products were examined, a nanocrystalline silver-coated dressing (SCD) and a gauze dressing impregnated with polyhexamethylene biguanide (PHMB), in in-vitro tests and an animal model of delayed wound healing. Both dressings were demonstrated to have potent in-vitro bactericidal effects. However, the PHMB dressing did not have any activity beyond its own borders, whereas the SCD demonstrated antimicrobial activity that diffused into the surrounding environment, as shown in zone of inhibition assays. In wound healing experiments, wounds dressed with the SCD dressing developed a full granulation bed much faster than those dressed with the PHMB dressing and also demonstrated a lower wound bioburden than those dressed with the PHMB dressing. These results suggest that in clinical use, simply being an effective antimicrobial is not sufficient to make a product the best choice to promote wound healing. This is consistent with results obtained with other topical antimicrobial products that may be effective against contaminating organisms but that may impede wound healing.

A porcine model of wound healing was employed to examine the impact of nanocrystalline silver-coated dressings on specific wound healing events. Full-thickness wounds were created on the backs of pigs, contaminated with an experimental inoculum containing Pseudomonas aeruginosa, Fusobacterium sp., and coagulase-negative staphylococci, and covered with dressing products either containing silver or not. Nanocrystalline silver-coated dressings promoted rapid wound healing, particularly during the first several days post-injury. Healing was characterized by rapid development of well vascularized granulation tissue that supported tissue grafting 4 days post-injury, unlike control dressed wounds. The proteolytic environment of wounds treated with nanocrystalline silver was characterized by reduced levels of matrix metalloproteinases. Matrix metalloproteinases have been shown to be present in chronic ulcers at abnormally high levels, as compared with acute wounds, and may contribute to the nonhealing nature of these wounds. Cellular apoptosis occurred at a higher frequency in the nanocrystalline silver-treated wounds than in wounds dressed with other products. The results suggest that nanocrystalline silver may play a role in altering or compressing the inflammatory events in wounds and facilitating the early phases of wound healing. These benefits are associated with reduced local matrix metalloproteinase levels and enhanced cellular apoptosis.

Matrix metalloproteinases (MMP) are part of a group of proteolytic enzymes that are important in various repair and inflammatory processes. Dysregulation of MMPs and other proteinases has been linked to a number of pathologic processes, including such chronic inflammatory disorders as rheumatoid arthritis, periodontal disease, and chronic wounds. Of the proteolytic enzymes, MMPs have received the most attention with regard to wound healing. MMPs appear to be important in acute wound healing. Differences exist between the amounts, timing, and distribution of MMPs and their inhibitors (tissue inhibitor of metalloproteinases [TIMPs]) in acute and chronic wounds. This suggests that this imbalance may be important in the development and duration of chronic wounds. In fact, alteration of the MMP/TIMP ratio changes with the healing of chronic wounds. Therapies used to treat chronic wounds may impact upon MMPs and their inhibitors, and attention to alterations of MMPs with therapy may be an important endpoint. Among those therapies that likely impact MMPs is the use of nanocystalline silver dressings. Animal studies have shown that nanocystalline silver dressings alter MMP expression. In this paper we will review MMPs, the role of MMPs in wound healing, and present preliminary data of the ability to alter MMP expression in chronic human wounds.

Background: Fungal infections of burn wounds have become an important cause of burn-associated morbidity and mortality. The nature of fungal infections dictates aggressive treatment to minimize the morbidity associated with these infections. Persons with large total body surface area burns are particularly susceptible to fungal infections and are treated in such a manner as to minimize their risk of infection. Methods: This study examined the in vitro fungicidal efficacy of a variety of different topical agents. By placing fungal inocula in contact with mafenide acetate, silver nitrate, silver sulfadiazine, and a nanocrystalline silver-coated dressing, we determined the kill kinetics of these topical agents against a spectrum of common burn wound fungal pathogens. Results: The topical antimicrobials that were tested demonstrated varying degrees of efficacy against these pathogens. Conclusion: The nanocrystalline silver-based dressing provided the fastest and broadest-spectrum fungicidal activity and may make it a good candidate for use to minimize the potential of fungal infection, thereby reducing complications that delay wound healing. (AJIC Am J Infect Control 1999;27:344-50)

This study was designed to assess the efficacy of silver-coated dressings in preventing Pseudomonas aeruginosa-related burn wound mortality in rats. Infection by P. aeruginosa remains a significant cause of burn wound sepsis. Antibiotic therapy has not been as successful as anticipated in controlling these organisms, prompting continued research into other treatment modalities, including topical agents, to prevent or reduce infection. Using a modified Walker-Mason technique, burn wounds were induced on rats by exposing an area of dorsal skin to boiling water for 12 seconds. Burn sites were covered with vehicle dressings, with vehicle dressings saturated with AgNO3, or with silver-coated dressings, and inoculated with P. aeruginosa. A Burn Control group and Infection Control group were also included. Mortality was monitored daily and body weight gain was assessed at several intervals throughout the 15-day post-wounding study. Mean percent survival of rats receiving the silver-coated dressings was 85 percent compared to five percent in the Infection Control group and zero percent in the Silver Nitrate Dressing and Dressing Control groups. Rats in all infected groups lost weight during the first three days, but mean body weight loss was significantly greater in AgNO3 and Dressing Control groups than in Silver-Coated Dressing groups. Mean body weights of animals in the Silver-Coated Dressing group were comparable to Burn Control rats at Day 15. The use of the dressings coated with nanocrystalline silver significantly improved rat survival in this animal model.

BACKGROUND Antibiotic-resistant bacteria represent an increasing concern in wound infections. Wound colonization with these organisms normally results in aggressive management of the wound complicated by a greatly limited choice of therapeutic antibiotics. Silver and other noble metals are recognized as potential allies in combating these organisms in wounds. METHODS Three types of topical silver applications were tested to determine their bactericidal efficacies against clinical isolates of antibiotic-resistant organisms. The silver-based applications represent 3 methods of applying silver to wounds: as a liquid (silver nitrate), incorporated in a cream (silver sulfadiazine) and as a dressing coating (silver-coated dressings). The reduction in the viable bacterial population recovered from test articles after exposure to silver provided a comparative measure of the bactericidal efficacies of these silver applications. RESULTS All of the products demonstrated an ability to reduce the number of viable bacteria. However, the methods varied in their efficacy against antibiotic-resistant bacteria, with the silver-coated dressing being the most efficacious and silver nitrate the least efficacious. CONCLUSIONS Silver was demonstrated to be effective at killing the antibiotic-resistant strains tested. The silver-coated dressing was particularly rapid at killing the tested bacteria and was effective against a broader range of bacteria. Silver may be a useful prophylactic or therapeutic agent for the prevention of wound colonization by organisms that impede healing, including antibiotic-resistant bacteria.

Modern wound dressings have been designed to promote wound healing by providing a moist wound environment. Concurrent with the development of these dressings, concern regarding the potential for increased wound colonization and subsequent infection under these dressings has also surfaced. As a result, manufacturers have developed a number of products that claim to help maintain a minimally contaminated wound bed. In an era of rapidly advancing antimicrobial resistance and related calls for the minimization of antibiotic use, silver is gaining increasing popularity as an effective antimicrobial agent. The most intriguing of the new silver-containing products utilize controlled silver release technologies. The antimicrobial efficacies of two of these products, one a film dressing and the other a silver-coated absorbent dressing, were compared against commonly encountered bacterial (including antibiotic-resistant strains) and yeast wound pathogens. The ability of the dressings to prevent bacterial growth after repeated challenge was also examined to derive an indication of the longevity of the dressings' efficacies. The nanocrystalline silver-coated dressing demonstrated a much faster bactericidal action against a broader spectrum of organisms in these in-vitro comparisons. These encouraging in-vitro results are currently undergoing confirmatory testing in vivo.