Abstract
Chronic wounds are susceptible to bacterial infections and at high risk of developing antibiotic‐resistant bacterial infections. Silver is an antimicrobial by targeting almost all types of bacteria in chronic wounds to reduce the bacterial load in the infected area and further facilitate the healing process. This study focused on exploring whether silver‐based dressings were superior to non‐silver dressings in the treatment of chronic wounds. PubMed, Web of Science and Embase were comprehensively searched from inception to March 2024 for randomized clinical trials and observational studies. The endpoints in terms of wound healing rate, complete healing time, reduction on wound surface area and wound infection rate were analysed using Review Manager 5.4 software. A total of 15 studies involving 5046 patients were eventually included. The results showed that compared with patients provided with non‐silver dressings, patients provided with silver‐based dressings had higher wound healing rate (OR: 1.43, 95% CI: 1.10–1.85, p = 0.008), shorter complete healing time (MD: −0.96, 95% CI: −1.08 ~ −0.85, p < 0.00001) and lower wound infection rate (OR: 0.56, 95% CI: 0.40–0.79, p = 0.001); no significant difference in the reduction on wound surface area (MD: 12.41, 95% CI: −19.59–44.40, p = 0.45) was found. These findings suggested that the silver‐based dressings were able to enhance chronic wound healing rate, shorten the complete healing time and reduce wound infection rate, but had no significant improvement in the reduction on wound surface area. Large‐scale and rigorous studies are required to confirm the beneficial effects of silver‐based dressings on chronic wound healing.
Keywords: bacterial infection, chronic wounds, silver dressings, wound dressing, wound healing
1. INTRODUCTION
Chronic wounds are those that fail to heal within an expected time frame and generate a significant burden to patients and healthcare systems due to their increasing incidence and cost. 1 Common chronic wounds include diabetic, pressure, arterial and venous ulcers, as well as chronic non‐healing wounds caused by trauma or surgical wounds. 2 Approximately 1%–2% of people will suffer a chronic wound at some point in their lives in developed countries and worldwide. 1 Recent studies would suggest that the number of wound patients increased by 70% with an increase of cost by 45% over a 5‐year period, and the chronic wounds may affect up to 5% of people and consume up to 10% of medical costs. 1 , 3
Patients with chronic wounds predispose to bacterial infections and are at high risk of developing antibiotic‐resistant bacterial infections. 4 , 5 It is generally acknowledged that, infection is a main cause for delayed healing and non‐healing of wounds. 6 , 7 Silver‐based dressings are the most commonly used wound dressings by targeting almost all bacteria to reduce the bacterial load in the infected wounds, inhibit the inflammatory responses and facilitate the healing process. 5 Silver nanoparticles, as an excellent and improved antimicrobial agent, have been integrated into wound dressings in the range of 1–100 nm. 5 This material has exhibited antimicrobial activity against multiple infectious and pathogenic microorganisms, even multidrug‐resistant bacteria. 8 To date, these silver‐based dressings have become increasingly popular for chronic wound healing in clinical practice. 9
Silver has come through a long history in treating wound, but meta‐analysis with sufficient evidence verifying the efficacy of silver and silver nanoparticle dressings in chronic wounds is lacking. Therefore, we conducted a meta‐analysis to compare the therapeutic effect of silver‐based dressings versus other non‐silver dressings for the treatment of chronic wounds in clinical settings.
2. METHOD
2.1. Search strategy
We searched PubMed, Web of Science and Embase from inception to March 2024 to identify studies that reported the silver‐containing dressings in the management of chronic wounds. The search strategy was as follows: ‘silver’ or ‘silver dressing’ or ‘silver nanoparticle’ or ‘silver‐based’ or ‘silver‐containing’ or ‘silver‐releasing’ and ‘chronic wound’ or ‘foot ulcer’ or ‘diabetic toot ulcer’ or ‘venous ulcer’ or ‘leg ulcer’ or ‘pressure ulcer’ or ‘surgical wound’ or ‘surgical injury’ or ‘wound infection’. Two reviewers independently reviewed the studies that met the inclusion criteria. Furthermore, we also screened the reference lists for additional eligible studies.
2.2. Inclusion and exclusion criteria
The inclusion criteria: (a) patients with chronic wounds that fail to heal within 30 days, including diabetic, pressure, arterial and venous ulcers, as well as chronic non‐healing wounds caused by trauma or surgical wounds; (b) patients treated with silver‐based dressings not limited to any type; (c) studies with sufficient data that at least reported one of required outcomes: wound healing rate, complete healing time, wound area reduction and wound infection rate. Wound healing was characterized by full epithelialization. The complete healing time referred to the average duration required for an ulcer to heal entirely. Reduction in wound surface area was quantified as the percentage decrease from original surface area to 8th week surface area. The rate of wound infection was determined by the percentage of wounds that either had a negative swab culture or clinically resolved infections without recurrence. The exclusion criteria: (a) studies without reporting required outcomes; (b) reviews, laboratory studies, conference abstracts and case reports; (c) studies with unavailable full text; (d) studies reported not in English.
2.3. Data extraction
Two reviewers independently gathered the data from included studies. After reviewing the titles, abstracts and full texts, the following information was extracted: baseline characteristics including first author, country, year of publication, study design, follow‐up time, chronic wound types, sample size and details of dressings; endpoints including wound healing rate, complete healing time, reduction of wound area and wound infection rate.
2.4. Statistical analysis
All analyses were performed using Review Manager 5.4 software. For dichotomous data, the results were evaluated with odds ratio (OR) and 95% confidence interval (CI). For continuous data, the effect size was determined by mean difference (MD) or standardized mean difference (SMD) and 95% CI. The heterogeneity for the included studies was tested by Chi‐Squared test. If I 2 value was less than 50%, and the fixed effect model was performed, indicating that no heterogeneity existed among the studies; otherwise, the fixed random model was adopted, indicating that heterogeneity existed. The difference was considered statistically significant with p‐value <0.05. A funnel plot was used to investigate publication bias when sufficient data in included studies were extracted.
3. RESULTS
3.1. Literature selection and characteristics of included studies
The flow chart of study literature process is shown in Figure 1. After comprehensive online searching from databases, 2754 related studies were found. On the basis of the inclusion criteria, 2371 studies were excluded by reviewing the titles, abstracts and study designs. Then, 368 studies were removed after detailed assessment of the full texts. Eventually, 15 studies 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 with a total of 5046 patients were enrolled for this analysis. Of these patients undergoing chronic wounds, 1560 patients were provided with silver‐based dressings (experimental group), while 3486 were treated with non‐silver dressings (control group). The baseline characteristics of included studies are presented in Table 1 and the meta‐analysed results are summarized in Table 2.
FIGURE 1.
Flow chart of study selection process.
TABLE 1.
Baseline characteristics of included studies.
| Case (n) | Intervention | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| First author | Country | Year | Study design | Follow‐up time | Chronic wound types | Sample size | Experimental | Control | Experimental | Control |
| Essa MS 10 | Egypt | 2023 | RCT | 12 weeks | Diabetic foot ulcer | 80 | 40 | 40 | Silver nanoparticles dressing | Conventional dressing |
| Lafontaine N 11 | Australia | 2022 | RCT | 12 weeks | Diabetic foot ulcer | 118 | 63 | 55 | Silver dressings | Non‐silver dressings |
| Lawrie K 12 | Czech Republic | 2022 | RCT | 30 days | Surgical incision | 218 | 109 | 109 | Silver‐based dressing | Conventional silver‐free dressing |
| Chen J 13 | China | 2021 | RCT | NR | Pemphigus vulgaris | 58 | 28 | 30 | Physiotulle Ag dressings | Povidone‐iodine dressings |
| Hurd T 14 | Canada | 2021 | Retrospective | NR | Open chronic wounds | 2572 | 330 | 2242 | Nanocrystalline silver dressings | Non‐nanocrystalline silver dressings |
| Connery SA 15 | The United States | 2019 | RCT | 6 weeks | Caesarean section | 657 | 328 | 329 | Silver nylon dressing | Identical‐appearing gauze wound dressing |
| Struik GM 16 | Netherlands | 2018 | RCT | 90 days | Breast cancer surgical incision | 230 | 106 | 124 | Aquacel® Ag dressing | Standard dressing |
| Gupta V 17 | India | 2018 | Prospective | 8 weeks | Diabetic foot ulcer | 30 | 15 | 15 | Nanocrystalline silver ion dressings | Normal saline dressings |
| Senet P 18 | 38 European centres in 5 countries | 2014 | RCT | 10 weeks | Venous leg ulcer | 181 | 87 | 94 | Biatain‐Ag | Biatain |
| Lazareth I 19 | France | 2012 | RCT | 8 weeks | Venous leg ulcer | 102 | 52 | 50 | Silver releasing contact‐layer dressing | Contact‐layer dressing without silver |
| Biffi R 20 | Italy | 2012 | RCT | 30 days | Colorectal cancer surgical incision | 112 | 58 | 54 | Aquacel® Ag Hydrofiber dressing | Standard dressing |
| Miller CN 21 | Australian | 2010 | RCT | 12 weeks | Venous leg ulcer | 281 | 140 | 141 | Nanocrystalline silver | Cadexomer iodine |
| Kerihuel JC 22 | France | 2010 | RCT | 4 weeks | Venous leg ulcer | 60 | 30 | 30 | Actisorb silver 220 | Hydrocolloid dressing |
| Michaels JA 23 | England | 2009 | RCT | 12 weeks | Venous leg ulcer | 213 | 107 | 106 | Silver‐donating dressings | Non‐silver dressings |
| Jude EB 24 | 18 European centres in 4 contries | 2007 | RCT | 8 weeks | Diabetic foot ulcer | 134 | 67 | 67 | Hydrofiber® dressings containing ionic silver | Algosteril® calcium alginate dressing |
Abbreviations: NR, not reported; RCT, randomized controlled trial.
TABLE 2.
Summary of the meta‐analysed results.
| Included studies | Sample size | OR | MD | Proportion of 95% CI | p value | I 2 (%) | p value | |
|---|---|---|---|---|---|---|---|---|
| Wound healing rate | [10–12, 17, 18, 21, 23, 24] | 1300 | 1.43 | ‐ | [1.10,1.85] | 0.08 | 38 | 0.13 |
| Complete healing time | [13, 14, 24] | 2756 | ‐ | −0.96 | [−1.08, −0.85] | <0.00001 | 97 | <0.00001 |
| Wound area reduction | [19, 24] | 301 | ‐ | 12.41 | [−19.59,44.40] | 0.45 | 76 | 0.04 |
| Wound infection rate | [11–16, 20, 22] | 4125 | 0.56 | ‐ | [0.40,0.79] | 0.001 | 0 | 0.54 |
3.2. Effect of silver‐based dressings on wound healing rate
The forest plot of effect of silver‐based dressings on wound healing rate is presented in Figure 2. There were eight studies 10 , 11 , 12 , 17 , 18 , 21 , 23 , 24 that reported the wound healing, and the pooled results suggested that compared with non‐silver dressings in the included studies, silver‐based dressings were more effective in promoting wound healing (OR: 1.43, 95% CI: 1.10–1.85, p = 0.008). No heterogeneity among the included studies was observed (I 2 = 38%, p = 0.13), then a fixed‐effect model was applied.
FIGURE 2.
Forest plot of effect of silver‐based dressings on wound healing rate.
3.3. Effect of silver‐based dressings on complete healing time
The forest plot of complete healing time is presented in Figure 3. According to the results of the wound healing time (days) reported in three studies, 13 , 14 , 24 the pooled results showed that silver‐based dressings were associated with a shorter complete wound healing time than non‐silver dressings (MD: −0.96, 95% CI: −1.08–0.85, p < 0.00001). There was a significant heterogeneity among the included studies (I 2 = 97%, p < 0.00001), then a random‐effect model was used.
FIGURE 3.
Forest plot of effect of silver‐based dressings on complete healing time.
3.4. Effect of silver‐based dressings on wound area reduction
The forest plot of wound area reduction is presented in Figure 4. Two studies 19 , 24 reported the relative reduction on wound area from original wound area to 8th week wound area. The pooled results showed that silver dressings did not significantly reduce the wound surface area compared to non‐silver dressings (MD: 12.41, 95% CI: −19.59–44.40, p = 0.45). Significant heterogeneity among the included studies was observed (I 2 = 76%, p = 0.04), then a random‐effect model was performed.
FIGURE 4.
Forest plot of effect of silver‐based dressings on wound surface area reduction.
3.5. Effect of silver‐based dressings on wound infection rate
The forest plot of wound infection rate is presented in Figure 5. Eight studies 11 , 12 , 13 , 14 , 15 , 16 , 20 , 22 comprising 4125 patients were included in this analysis. The pooled results (OR:0.56, 95% CI:0.40–0.79; p = 0.01) indicated that silver‐based dressings were more beneficial in reducing infection rate than non‐silver dressings. No heterogeneity among the included studies was observed (I 2 = 0%, p = 0.54), then a fixed‐effect model was performed.
FIGURE 5.
Forest plot of effect of silver‐based dressings on wound infection rate.
3.6. Publication bias
To examine the reliability of the results, the funnel plots were adopted to detect publication bias. Specifically, the included studies on wound healing rate and infection rate were analysed for publication bias, while the funnel plots of wound healing time and wound area reduction could not be conducted due to the insufficient data provided by the included studies. The results of the publication bias assessment demonstrate no significant publication bias in the analysis of the wound healing rate and infection rate, as the studies were symmetrically distributed (Figure 6).
FIGURE 6.
Publication bias. (A) Funnel plot of wound healing rate; (B) Funnel plot of wound infection rate.
4. DISCUSSION
This study evaluated the effect of silver and silver nanoparticle dressings in the management of chronic wounds. The results revealed that silver‐based dressings were able to enhance chronic wounds healing rate, shorten the complete healing time and reduce the wound infection rate, while they had no significant effect on reduction of wound area compared to non‐silver dressings.
Chronic wounds are very susceptible to infections, which take billions of dollars to investigate new antibiotics for the bacterial infection; however, bacterial resistance against antibiotics is continuously rising. 25 In this context, silver and silver nanoparticles can be great promising strategies for reducing infection risk and improving the healing rate of chronic wounds due to their antibacterial, anti‐oxidative and anti‐inflammatory properties. 26 , 27 , 28 In a recent randomized controlled study, the polyurethane dressing containing silver particles was shown to be more effective in reducing the infection rate in patients with diabetic foot ulcers (DFUs) compared to the simple sterile dressing. 29 For the treatment of other chronic wounds such as venous leg ulcer, pemphigus vulgaris and incisional wound, silver‐containing dressings can also accelerate the wound healing and reduce wound infection compared to conventional non‐silver dressing. 12 , 13 , 30 These findings are consistent with the conclusion of our study. Moreover, the nanocrystalline silver dressings have reported an improved efficacy and cost‐effectiveness for chronic wound management. 14 Of note, a large randomized controlled trial, which was quite different from others, identified that silver dressings showed no benefit in wound healing and ulcers infection in DFUs. 11 The efficacy of silver‐based dressings on chronic wound healing remains controversial. In this study, our results suggested that compared with patients treated with non‐silver dressings, patients treated with silver‐based dressings had higher wound healing rate, shorter complete healing time and lower wound infection rate, but no significant effect on wound area reduction was found. These findings are consistent with the results reported in a previous meta‐analysis in DFUs. 31 However, Essa et al. 10 found that silver nanoparticles dressings are more effective in reducing ulcer area by the 8th, 10th and 12th weeks, compared to the conventional dressings. In their study, surface area was calculated using Mayrovitz formula (A [area] = L [length] × W [width] × 0.785), and healing area was determined by subtracting the remaining ulcer surface area at each time point from the baseline. Conversely, Lazareth et al. 19 and Biffi et al. 20 did not specify their methods for measuring ulcer surface area, but they both presented healing area as 100 × [(original wound area—final wound area)/original wound area]. Lazareth et al. 19 reported that the wound surface area decreased by a median of 47.9% in the silver‐releasing contact‐layer dressing group, compared to 5.6% in the contact‐layer dressing without silver group by the 8th week. Nevertheless, Biffi et al. 20 demonstrated that AQUACEL® Hydrofiber® dressings containing ionic silver (AQAg) had a comparable ulcer area reduction rate to Algosteril® calcium alginate (CA) dressings (58.1% vs. 60.5%) by the 8th week. Therefore, the effectiveness of silver‐based dressings in reducing wound area remains controversial and needs further investigation.
This meta‐analysis had several limitations despite the comprehensive analyses and encouraging results of silver‐based dressings for chronic wound healing. Firstly, the data available are limited due to varying endpoint criteria, which made effective sub‐analysis hard to perform and may affect the generalizability of pooled results. Secondly, the different types of chronic wounds, different follow‐up time and different silver‐based antimicrobial dressings among the 15 included studies might be the causes of the heterogeneity in terms of complete healing time and wound healing area. Finally, a significant wound area reduction was not detected in this meta‐analysis, therefore, more clinical trials and studies are needed to support this result.
5. CONCLUSION
In conclusion, this study showed that the silver‐based dressings were able to enhance chronic wound healing rate, shorten the complete healing time and reduce the wound infection rate compared to non‐silver dressings. Although there was no significant improvement on reduction of wound area, these findings may provide a reference for choosing an optimal wound dressing to facilitating the healing of chronic wounds. Large‐scale and multicenter studies are still required to justify the beneficial effects of silver‐based dressings on chronic wound healing.
CONFLICT OF INTEREST STATEMENT
The authors declare that there is no competing interest associated with the manuscript.
Liang K, Liu Y, Jiang F. Analysis of therapeutic effect of silver‐based dressings on chronic wound healing. Int Wound J. 2024;21(8):e70006. doi: 10.1111/iwj.70006
Kaitao Liang Lead author.
DATA AVAILABILITY STATEMENT
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.