Comparative Efficacy of Silver-Containing Dressing Materials for Treating MRSA-Infected Wounds in Rats with Streptozotocin-Induced Diabetes

Objective. Silver plays an important part in severe wound management, mainly by reducing microbial growth within dressed wounds and wound beds. However, it is unknown how silver-coated dressing materials affect diabetic wounds. The purpose of this study is to evaluate the efficacy of silver-containing dressing materials for the treatment of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds in streptozotocin-induced diabetic rats. Methods. Full-thickness skin defects were created on the backs of rats with streptozotocin (STZ)-induced diabetes (n = 108) and were infected with MRSA. The rats were assigned to 6 groups according to the wound dressing used: nanocrystalline silver (Acticoat, Smith & Nephew, Inc, London, UK), silver carboxymethylcellulose (Aquacel-Ag, ConvaTec, Skillman, NJ), silver sulfadiazine (Medifoam silver, Genewel Science Co Ltd, Seongnam, South Korea), nanocrystalline silver (PolyMem silver, Ferris Mfg Corp, Burr Ridge, IL), silver sulfadiazine (Ilvadon, Ildong Pharmaceuticals, Seoul, South Korea), and 10% povidone iodide (control). The wound size, histological findings, and bacterial colony count for each group was analyzed and compared to normal Sprague–Dawley rats. Results. Wound size decreased over time in every group. On day 10, a significant difference in wound area was detected between the silver dressing groups and the control group (P = 0.0040). In the wound biopsy, on days 4, 7, and 10, the would-healing effect increased in every group. However, between days 4 (P = 0.8250) and 10 (P = 0.9912), there was no statistical difference between groups. The number of bacteria in each group decreased with time in the bacterial wound culture. The silver dressing groups were more effective on antimicrobial efficacy, but there was no statistically significant difference between the silver dressing groups and the control group. Conclusion. Silver-containing dressing materials are an effective method for MRSA-infected wounds, but nano silver-containing dressing materials did not have better results in a diabetic rat model compared to a normal rat model in historical review. Further investigation is necessary to determine the relative safety of these products on the healing wound. Once that is done, the relative value of the products can be determined by balancing their antimicrobial and cytotoxicity characteristics.

  Wound dressing materials should be carefully selected based on the strain of infecting bacteria. Since the first identification of methicillin-resistant Staphylococcus aureus (MRSA) in the United Kingdom in 1961, domestic MRSA infections have increased worldwide and are becoming a problem in wound treatment.^1-3   Silver-based dressings are one treatment method for MRSA-infected wounds. Silver possesses a broad range of antibacterial activity, and has been used to treat wounds, burns, and ulcers for many centuries.^4,5 It has been reported that low concentrations of silver ions cause little cytotoxicity or skin discoloration, but that silver-based dressings are toxic to cultured human epithelial cells; furthermore, little is known about the long-term effects of silver on the human body.^4,5 Several reports^5,8,14 have addressed the effects of silver-based dressing materials, but few studies have compared these dressings. In particular, reports on the use of such dressings in diabetic patients are rare. In 2006, Bolton⁶ reported no significant difference in adverse effects due to silver dressings when compared with traditional or modern dressings in patients with diabetic foot ulcers. In 2010, Sharma et al⁷ found that diabetes aggravated silver nanoparticle-induced neurotoxicity.   To the best of the authors’ knowledge, the use of silver dressings has not been investigated in diabetic rats. This study compares the wound healing effects of silver-based dressings with control 10% povidone iodide dressings on full-thickness skin defects in MRSA-infected diabetic rats. The results between normal Sprague–Dawley rats and streptozotocin (STZ)-induced diabetic rats are also compared.⁸

  Female Sprague–Dawley rats with STZ-induced diabetes, 8 weeks old and weighing 150–250 g each (n = 108), were used. All animals were maintained under a standardized light/dark schedule and housed in individually ventilated cages. All animal procedures were approved by the Soonchunhyang University Hospital, Buncheon, South Korea, Institutional Committee for the Care and Use of Animals in Research and Education, and the animals were treated in accordance with the guidelines issued by the National Institutes of Health and United States Department of Agriculture.   The rats were housed individually in clear-sided cages at a controlled temperature (22 ± 2°C, 50 ± 20% humidity) under a 12-hour light/dark cycle, and had free access to water and rat chow over a 1-week adaptation period. The body weight of the animals was measured twice (at STZ injection and blood glucose measurement). The diabetic rats were fasted for 16 hours before the injection of STZ. The rats received 2 intraperitoneal injections using a sterile 23-G needle of 40 mg/kg STZ (Sigma-Aldrich, St. Louis, MO), which was freshly dissolved in 0.01 M citrate buffer (pH 4.5). During the injection, the rats were held in 1 hand in the dorsal position. The blood glucose level was determined using a handheld meter system (Accu-Chek Performa, Roche Diagnostics, Basel, Switzerland) with blood taken from the tail vein at 2 weeks after the injection of STZ. The MRSA strain ATCC 43300 was used as the standard; a bacterial suspension with a turbidity of 0.5 McFarland was used.   Nanocrystalline silver (Acticoat, Smith & Nephew, Hull, UK), silver carboxymethylcellulose (Aquacel-Ag; ConvaTec, Skillman, NJ, USA), silver sulfadiazine (Medifoam silver; Biopol, Seoul, Korea), nanocrystalline silver (PolyMem silver; Ferris Mfg Corp, Burr Ridge, IL), and silver sulfadiazine (Ilvadon; Ildong Pharmaceutical Co Ltd, Seoul, South Korea) were used as silver-based dressing materials. A 10% povidone iodide solution (Betadine, Sungkwang Pharmaceutical Co Ltd, Bucheon, South Korea) was used as the control.   The MRSA standard strain was inoculated at a turbidity of 0.5 McFarland on 6 Mueller-Hinton agar plates. The previously mentioned 6 types of dressing materials (0.5 cm x 0.5 cm) were attached to each plate and incubated for 24 hours at 37°C. The antibacterial activities of the dressings were compared based on the sizes of the zones of inhibition on the plates.   Rats with STZ-induced diabetes were anesthetized, and after sterilization with alcohol, were shaved and full-thickness skin defects (1 cm²) were created. Methicillin-resistant Staphylococcus aureus (0.1 mL) with a turbidity of 0.5 McFarland was dropped onto the skin defects, which were covered with gauze impregnated with petroleum jelly (2 cm x 2 cm) to promote bacterial growth and prevent drying. The petroleum jelly-impregnated gauze was sealed using transparent waterproof adhesive film (Opsite, Smith & Nephew, Inc, London, UK) and fixed with tape.   Wound treatment. The STZ-induced diabetic rats were divided into 6 groups of 18 rats each, based on the treatment regimen: Acticoat (Ac), Aquacel-Ag (Aq), Medifoam silver (M), PolyMem silver (P), Ilvadon (I), and Betadine (B). At 24 hours after inoculation, the film was removed and the dressing materials (1.5 x 1.5 cm) were attached to the defects in groups Ac, Ag, M, and P, while the indicated medicines were applied to gauze (1.5 x 1.5 cm) and put on the defects in groups I and B. All defects were covered with gauze, sealed with film, and fixed with tape. The dressings were applied at 3-day intervals from day 4 after defect induction.   Wound size measurement. On days 4, 7, and 10 after defect induction, sterilized transparent films were placed over the defects; the outlines were traced and scanned for measurement using an image analysis system (Image Tool Version 2.01 Alpha 4, Microsoft, Redmond, WA). As a standard for comparison of the healing defects, the authors measured a 1 cm² area. The areas were converted to the percentage of the area on day 1 after defect induction, and the changes were compared. On day 4, there were 18 rats in each group; on day 7, there were 12; and on day 10, there were 6.   Wound biopsy. On days 4, 7, and 10 after defect induction, 3 STZ-induced diabetic rats were sacrificed and tissues were removed, including the entire defect and surrounding tissues. The tissues were fixed in 10% formalin for > 6 hours and stained with hematoxylin and eosin. The degrees of reepithelialization, granulation tissue formation, necrosis, and inflammation were determined by optical microscopy. The extent of reepithelialization and granulation tissue formation was classified from 0-3 as follows: (0) no reepithelialization or granulation tissue formation; (1) no more than 1/3 of the defect showed reepithelialization or granulation tissue formation; (2) 1/3–2/3 of the defect showed reepithelialization or granulation tissue formation; and (3) at least 2/3 of the defect showed reepithelialization or granulation tissue formation. The degrees of necrosis and inflammation were scored from 0 to -3 as follows: (0) no necrosis or inflammation (ie, like normal skin); (-1) inflammatory cells (eg, neutrophils) present without forming colonies; (-2) mixed small colonies or inflammatory cells without clear colonies; and (-3) large colonies of inflammatory cells. The total scores for reepithelialization, granulation tissue formation, necrosis, and inflammation in the stratum corneum and epithelium ranged from -6 to +6; the higher the score, the better the wound-healing effect.   Bacterial wound culture. On days 4, 7, and 10 after defect induction, 3 STZ-induced diabetic rats were sacrificed and biopsies were taken from the open defects for bacterial culture. One gram of tissue was homogenized then washed twice in phosphate-buffered saline with centrifugation for 5 minutes at 1,500 rpm. The washed suspension (0.001 mL) was inoculated onto a blood agar plate, cultured for 24 hours at 35°C, and the number of bacterial colonies determined.

  All data are expressed as the mean ± SD. Statistical analyses were performed by one-way analysis of variance (ANOVA), followed by Tukey’s test to correct for multiple comparisons. A level of significance of 5% was chosen to denote the difference between group means. All statistical analyses were conducted with SAS software, version 9.2 (SAS Institute, Cary, NC). All tests were two-sided.

  The body weight of each group of rats was 150–250 g, but there was no significant difference between the groups (Table 1). In addition, no difference in blood sugar was detected between the groups (Table 2).   The wound sizes all decreased in general with time but with differences in the form of decrease. When looking at the size of the wounds, the ones in groups Aq, Ac, P, M, and I reduced by day 4, 7, and 10 but the wounds in group B slightly increased with 78.23% (± 8.17) on day 4; 47.63% (± 19.27) on day 7; and 53.88% (± 9.66) on day 10. Therefore, the wound size decreased between day 7 and day 10, in the following order from greatest reduction in size to least reduction in size: I, Ac, Aq, M, P, and B. On day 10, the size of the wound was significantly bigger in the control group when compared to the group of silver-containing dressing materials, but without difference among silver groups. Therefore, there was no statistical significance in the differences in the wound area among the 6 groups using silver-containing dressing materials, but there was 1 when compared to the control group (two-way ANOVA, P = 0.0040) (Figure 1) (Table 3).   Wound biopsy. Reepithelization and formation of granulation tissue increased over time while inflammation decreased (Figure 2). When each state was compared, reepithelization increased from day 4 to day 7 to day 10 in groups Aq, P, M, and I, and even in the control group B, with the scores of 0.83 (± 0.41) on day 4, 1.50 (± 0.84) on day 7, and 1.33 (± 0.52) on day 10 (Table 4).   The degree of the granulation tissue formation increased in groups Aq, Ac, P, M, and I, from day 4 to day 7 to day 10. The control group showed better results with 1.17 (± 0.41) on day 4; 2.00 (± 0.00) on day 7; and 2.17 (± 0.75) on day 10. The control group also showed slightly less recovery compared to other silver-containing dressing materials but without statistical significance (P = 0.6573) (Table 5).   The degrees of necrosis were measured from -3 to 0, and all groups, including the control, showed less necrosis from day 4 to day 7 to day 10. However, the degrees of necrosis showed no great statistical significance between groups (P = 0.4926) (Table 6). Finally, the degrees of inflammation in all groups, including the control, decreased from day 4 to day 7, to day 10. There was no statistical significance found between groups (P = 0.5051) (Table 7).   The total score of the biopsy of the wound increased in all groups, including the control, from day 4, to day 7, to day 10. In general, the group treated with Ac had favorable results, while the group treated with Aq had no better results than the other groups treated with silver dressings. On day 10, every silver-containing dressing material group had better results than the control group, although the Ac group showed statistical significance (P = 0.4483) (Figure 3) (Table 8).   Bacterial wound culture. Bacteria in the wounds was measured by bacterial colony. The bacterial culture counts in the Aq group increased on day 7, while decreasing by day 10. Counts were 364833 (± 267380) on day 4; 771833 (± 853403) on day 7; and 118733 (±207325) on day 10. The same was observed in the Ac group with 127833 (±267380) on day 4; 555833 (± 502010) on day 7; and 186083 (± 407375) on day 10. The P group had bacterial counts of 300833 (± 284366) on day 4; 741667 (±687857) on day 7; and 111667 (±126359) on day 10. The M group had 168333 (± 147383) on day 4; 273333 (± 287362) on day 7; and 107617 (±217544) on day 10. For the I group, bacterial counts were 320000 (± 234989) on day 4; 612500 (± 371561) on day 7; and 4025 (± 4517) on day 10. The control group had 292500 (± 158863) on day 4; 236667 (± 201660) on day 7; and 19500 (± 18426) on day 10.   The authors found it unusual that the average number of bacterial colonies increased in every group on day 7 and decreased on day 10. In the control group, fewer bacterial colonies were observed compared to the silver-containing dressing groups, which all showed increased numbers of colonies on day 7 and a decreased number on day 10. The result of the largest number of colonies in the Ac group on day 10 is considered to be opposite of the existing results using normal rats.⁸ However, there was no statistical significance in the differences among groups (two-way ANOVA, P = 0.6467) (Figure 4) (Table 9).

  This study is the first to see the efficacy of silver-containing dressing materials on MRSA-infected wounds made by applying MRSA to the wounds in rats with STZ-induced diabetes.   This study used the methods described by Lee et al⁸ in an attempt to determine if there is any difference between the normal Sprague–Dawley rat model used in that study, and the STZ-induced diabetic rat model used in the current study. Lee and colleagues reported that silver-containing dressings had a greater antibacterial effect and increased wound healing rates on normal rats when compared to a 10% povidine iodide control. Out of the silver-containing dressings, Ac had the best results. Lee and coauthors concluded that dressing materials containing nanocrystalline silver particles, rather than regular silver particles, helped improve results; however, the outcomes from the P dressing, which contained the same nanocrystalline silver particles as the Ac dressing, were worse than the Aq dressing.   Lee et al⁸ considered this a result of the difference in the dressing materials, which is the difference in the mechanism of action of hydrofiber of Aq dressing.   In the current study, the results using the same dressing materials with the diabetic rat model were compared and found to be different from the results Lee and colleagues found with the normal rat model. Wound size generally decreased with time but in different ways than the normal rat model. In the normal rat model the difference between each dressing material was significant, especially when compared to the control,⁸ but in the current study, there was no significant difference observed among the dressings, only when they were compared to the control (P = 0.0040).   There was also a significant difference among each dressing material in the results of the wound biopsy in the normal rat model.   In the current study, the wounds healed over time in every group including the control, and favorable results were observed in every group treated with silver-containing dressing materials when compared to the control group on day 10. This, despite the fact that the control group showed relatively better healing results on day 7, but without statistical significance when compared to the silver-containing dressing groups (P = 0.4483).   Existing results^6,10 show that silver-containing dressing materials are effective on MRSA and help with wound treatment; because of this, the current study’s results were surprising. One possible explanation for this is the importance of the dose of silver on cells in diabetic wounds. In their study of in vitro cytotoxicity on fibroblasts in diabetic wounds, Zou et al⁹ concluded that low concentration of silver ion brings less cytotoxicity. Other studies have also found similar results.^6,10   The current study measured cultured bacteria counts extracted from wounds. In every group, the average number of colonies increased on day 7 and decreased on day 10. Smaller numbers of colonies were observed in the control group compared to the groups treated with silver-containing dressing materials. Cytotoxicity helps us understand these results.   Silver exists in nature as a ratio of 2 isotopes, Ag¹⁰⁷ and Ag¹⁰⁹, and there are 3 oxidation states: Ag⁺, Ag²⁺, and Ag³⁺. Of these, only Ag⁺ is soluble in water. The following silver-containing wound care materials release free silver ions in the presence of wound fluid: ionic silver, the active Ag⁺ form; elemental (metallic) silver (Ag⁰) in the form of nanocrystalline particles or foil; inorganic compounds or complexes such as silver nitrate or silver sulfadiazine; and organic complexes such as colloidal silver or silver-protein complexes.¹¹ Silver metal and most silver compounds ionize in water, body fluid, and tissue exudates, liberating antibacterial Ag⁺ or other forms of biologically active silver ions, or they are absorbed by adjacent body tissues. Silver ions adhere strongly to proteins and anions, and adhere to receptor groups on the surface of adjacent cells, bacteria, and fungi.¹⁰ Silver ions must be liberated to effectively kill pathogenic microbes using silver compounds. Silver ions show bactericidal action against a broad range of bacteria, including antibiotic-resistant species. The sites of action on the bacteria are diverse, and antibacterial activity occurs at low concentrations; therefore, it is believed that the chance of resistant strains appearing is very low.^4,12,13 Silver nitrate and silver sulfadiazine have been developed for inclusion in silver-based dressing materials; however, silver nitrate has the disadvantage of delaying wound healing by inducing tissue irritation, so silver sulfadiazine has mostly been used since the 1960s.¹² Silver sulfadiazine is now widely used as a burn treatment, and was first applied to burns in 1968. The silver compound in silver sulfadiazine becomes inactivated by wound exudates, so there is the inconvenience of changing dressings often; moreover, there are disadvantages in terms of wound discoloration, false eschar formation, irritation of the skin, and rapid inactivation.^12,14   Polyurethane-foam-dressing materials (the M and P dressings), were included in this study. Existing polyurethane foam dressing materials have the advantages of stimulating reepithelialization by enhancing epithelial cell movement, and by absorbing exudates from the wound, maintaining a moist environment on the wound surface. However, their application to infected wounds is limited since they contain no antibiotics and do not promote the degradation and detachment of false eschars.^15-17   The M dressing has silver sulfadiazine added to its existing surface. There is no contact layer to increase the absorptive power; however, the polyurethane dressing has small micropores (50-100 mm) containing silver sulfadiazine in the absorptive layer, which prevents epithelial cells from entering the micropores and prevents the dressing from sticking to the wound. In the present study, M had a better wound healing effect and rate of wound-size decrease than any of the other materials, and it was associated with moderate inflammatory cell infiltration in a biopsy of defect tissue. This suggests that more consideration is needed in regard to the relationship between the concentration of silver sulfadiazine and the absorptive power of foam-dressing materials. In other words, higher concentrations of silver sulfadiazine can better prevent infection, but there is the possibility of lowered absorption; thus, the structural problems of foam-dressing materials should be considered. In STZ-induced diabetic rats, the results for the M group differed from those in normal control rats.   Lee et al⁸ reported the M dressing exhibited inferior wound healing and a lower rate of wound size reduction than other materials in normal Sprague–Dawley rats. However, STZ-induced diabetic rats showed comparatively good results. It appears that inorganic compounds or complexes such as silver nitrate and silver sulfadiazine have better results in STZ-induced diabetic rats than in normal Sprague–Dawley rats. Additionally, the possibility of a secondary infection should be considered. Rats with diabetes are immunologically weaker than normal rats, so they are susceptible to secondary infections. Thus, it is expected that materials consisting of smaller micropores of polyurethane (eg, M) would show better results than other materials.   The P dressing has nanocrystalline silver particles added to the nonsilver-containing version of the dressing, a hydrophilic, semipermeable thin layer of polyurethane. Lee et al8 reported that P exhibited effective antibacterial activity against MRSA and wound healing, unlike M, which is a similar but less-effective foam dressing material. In this study, P was superior to Ac but inferior to M. This could have been due to differences between the silver sulfadiazine and nanocrystalline silver particles included in the polyurethane foam dressings in relation to their antibacterial activity against MRSA and their wound healing effect. In normal Sprague–Dawley rats, nanocrystalline silver particles showed effective bactericidal activity and reduced cytotoxicity. Burd et al¹⁸ found the silver content of P to be 139 µg/cm², which is 10-fold higher than that of an antibacterial foam dressing (Contreet Foam, Coloplast Corp, Minneapolis, MN). However, P had less apparent cytotoxicity than the antibacterial foam material. Nevertheless, the authors conclude that in diabetic rats a high silver concentration is cytotoxic to the normal flora and may promote secondary infections in injured normal tissue. Several studies have described the cytotoxicity of silver dressing materials.^6,9,18 However, these studies did not address the cytotoxicity of silver dressing materials in vivo, and they tested a small number of materials in vitro. It is assumed that diabetic rats differ from normal rats because of their immunological weakness and the secondary infection of normal tissues due to fatal cytotoxic effects on the normal flora.   The Ac dressing is one of many recently developed silver-based dressing materials. It is composed of 3 layers of polyethylene mesh, nanocrystalline silver, and 2 layers of rayon polyester.¹⁴ This dressing compensates for the weakness of existing materials by releasing a constant concentration of silver ions in the form of Ag⁰ for more than a few days; this form is less irritating and more durable than Ag⁺, and Ac prevents the inactivation of silver compounds by not binding to halides in the wound.^14,19 Lee et al⁸ reported that Ac had better antibacterial activity against MRSA and wound-healing effects than other silver-based dressing materials in normal rats. However, it does not absorb exudates; thus, secondary dressings are needed, and should be applied with distilled water. In the current study, Ac was inferior to the other materials. As mentioned above, this seems to be because the Ag⁰ in nanocrystalline silver is inferior for wound healing, and its cytotoxic effects also play an important role. Poon and Burd²⁰ reported that Ac had significant cytotoxic effects on both keratinocytes and fibroblasts. These data support the current findings.   The Aq dressing has silver ions included in the nonsilver-containing version of the dressing; it exerts antibacterial activity when the hydrofibers melt by absorbing exudates to release the incorporated silver ions. The Aq dressing retains the advantages of its nonsilver-containing version, including reduced cytotoxicity, reduced pain when changing the dressing, and the ability to keep the wound moist. There are reports that Aq causes less pain when sterilizing, takes less time to apply, and requires less-frequent dressing changes; thus, it is more cost-effective and carries a reduced chance of scarring.²¹   The contents, release, and antibacterial activities of Aq, Ac, P, and other silver-based dressing materials against S. aureus and Pseudomonas aeruginosa have been compared. The Ac dressing had a higher silver content than Aq and P, while Aq had a lower silver content than P. The release of silver was highest for Ac, and Aq released less silver than P, but the antibacterial activity was higher for Aq and Ac than for P. Lee et al⁸ reported that Aq and Ac both showed good antibacterial activity against MRSA and wound-healing efficacy, similar to the previous study on S. aureus and P. aeruginosa. They also showed better effects than P, which contains nanocrystalline silver particles like Ac. However, in the current study, the results were different from those in normal rats.   In this study, most of the silver-based dressing materials showed significant wound-healing efficacy and antibacterial activity in wounds infected with MRSA when compared with the control group, and there were differences between the silver-based dressing materials. However, the antibacterial effect against MRSA did not differ significantly among the silver-based dressing materials. In normal rats, Ac exhibited the best efficacy. The Ac and P dressings, which contain nanocrystalline silver particles, were more effective than the M and I dressings, which contain silver sulfadiazine; thus, it is believed that nanocrystalline silver particles are more effective. The results in diabetic rats differed from those in normal rats. The authors suggest this was due to the increased cytotoxicity of nanocrystalline silver particles, which affected the normal flora and facilitated secondary infection of the injured tissue.   As a method of treating wounds infected with MRSA, which is problematic for in-hospital infections, silver-based dressing materials are effective, and Ac is most effective in terms of its antibacterial and wound-healing effects among the many silver-based dressing materials used in normal rats. However, diabetes is a different situation. To the best of the author’s knowledge, an in vivo diabetic rat study using silver-dressing materials has not been performed. Sharma et al⁷ reported that diabetes aggravated silver nanoparticle-induced neurotoxicity.

  First, more extended research may be required because of the limited number of experimental animals. Also, diverse silver-containing dressings could not be measured since the number of dressing materials was limited.   Second, the current study had different results from another study with the normal rat model, using the same design and same materials; the differing results are considered to have come from a secondary infection. The current study was performed in a clean condition, with an effort to reduce the bias from the secondary infections, but the possibility can’t be excluded.   Finally, it is difficult to conclude that silver-containing dressing materials have a cytotoxic effect on diabetic wounds from the results of this study, even though the authors observed enough evidence of cytotoxic effect. Therefore, another study to prove this cytotoxicity is needed. Furthermore, it should be noted that patients’ factors should be considered important in choosing the optimal dressing materials for the wound treatment.

  Silver-containing dressing materials are considered useful for the treatment of MRSA-infected wounds. However, nanocrystalline silver-containing dressing materials had worse results when compared to the results of using the nanocrystalline silver-containing dressings on normal rat models, even though they showed relatively favorable results in diabetic rats compared to a control group treated with 10% povidone iodide in this study. Therefore, it should be noted that application of silver-containing dressing materials to diabetic wounds could bring different results compared to the use in non-diabetic wounds.

  This research was supported by the Basic Science Research Program through the National Research Foundation of Korea.

Jong Hoon Lee, MD is from Eulji University School of Medicine, Eulji General Hospital, Seoul, Republic of Korea. Jeong Ja Kwak, MD; Young Koo Lee, MD; Eui Dong Yeo, MD; and Seong Seok Yang, MD are from Soonchunhyang University Hospital, Gyeonggi-Do, Republic of Korea. Hee Bong Shin, MD is from Soonchunhyang University, Gyeonggi-Do, Republic of Korea. Hae Won Jung, MD is from Incheon Sarang Hospital, Incheon-Si, Republic of Korea.

Address correspondence to: Young Koo Lee, MD Department of Orthopedic Surgery, Soonchunhyang University 4 Jung-Dong, Wonmi-Gu, Bucheon-Si, Gyeonggi-Do, 420-767, Republic of Korea brain0808@hanmail.net

Disclosure: The authors disclose no affiliation with the manufacturers or products mentioned in this study. This work was funded by the Ministry of Education, Science and Technology (2011-0013275) and partially supported by the Soonchunhyang University Research Fund.