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Absorption and swelling characteristics of silver (I) antimicrobial wound dressings Dharnidhar V Parikh, Tom Fink, Anthony J DeLucca and Ashish D Parikh Textile Research Journal 2011 81: 494 originally published online 8 September 2010 DOI: 10.1177/0040517510380778 The online version of this article can be found at: http://trj.sagepub.com/content/81/5/494

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Original article

Absorption and swelling characteristics of silver (I) antimicrobial wound dressings

Textile Research Journal 81(5) 494–503 ! The Author(s) 2010 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0040517510380778 trj.sagepub.com

Dharnidhar V Parikh1, Tom Fink1, Anthony J DeLucca1 and Ashish D Parikh2

Abstract An important characteristic of moist wound dressings is their ability to swell and absorb exudates from the wound, while maintaining a moist atmosphere at the wound site. At the SRRC, we have previously developed antimicrobial silversodium-carboxymethylated (CM)-cotton printcloth from the sodium salt of CM-cotton, and silver-Ca-Na alginates from four commercially available alginate moist wound dressings. As part of ongoing research on silver antimicrobials, this report delineates the swellabilty of these silver antimicrobial dressings compared to commercially available calciumsodium alginate dressings and printcloth (controls) in water and in 0.9% sodium chloride solution (saline) after 8 hours and after one week of immersion. Additionally, the swelling characteristics are correlated with the absorption of saline g/g of the dressing. Silver treated Sorbsan, Kaltostat, Curasorb, Algisite, and cotton-CM-printcloth showed a very significant increase in diameter of the fibers: NaCl 8 hr > water 8 hr > dry, albeit slightly less than the control alginate dressings. The majority of the swelling took place in the first eight hours of wetting, and continued wetting for one week caused little additional uptake of the solution. Fibers swell only in diameter and not in length. All the fibers had greater swelling in saline as compared with those in water. The proven swellabilty of these silver dressings, taken together with the known absorptive and antimicrobial properties of the dressings should make them suitable for treatment of exudative wounds that are at risk for infection. As more is learned about these dressings, clinical trials may be warranted to evaluate their efficacy.

Keywords Infected wounds, silver antimicrobial, alginate wound dressings, swelling, absorption, occlusive dressings, moist wound dressings

Introduction Alginate dressings are one of the most versatile wound dressings because of their unique gel-forming properties and high absorption capabilities.1 They meet with the concept of forming occlusive dressings when used on wounds that are moderate-to-highly exudating. Occlusive dressings are developed on the basis of the pioneering work of Winter,2,3 who published work on the effects of occlusion on the rate of epitheliazation on the surgically created wounds (on porcine model) when left to heal either open in air or occluded under a transparent film. The rate of epitheliazation under occlusive dressing was twice as fast as that of the wounds left undressed. Occlusive dressings limit the transmission of water vapor, and gases to the external environment, and thereby maintain a moist environment on the

surface of most wounds.4 Wounds heal better in a moist environment. Moisture prevents desiccation and hence epithelial cell death. Moisture also facilitates epidermal migration, angiogenesis, and connective tissue regeneration.5 All occlusive dressings provide the benefits of insulation, mechanical protection, and act as a barrier against bacteria.6 It is suggested that the scar

1 2

USDA-ARS-SRRC, New Orleans, LA, USA. Saint Barnabas Medical Center, Livingston, NJ, USA.

Corresponding author: Dharnidhar V Parikh, USDA-ARS-SRRC, 1100 Robert E. Lee Blvd, New Orleans 70124, LA, USA Email: [email protected]

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left by an occlusive dressing is more cosmetically acceptable than that left by an exposed wound.7,8 Occlusive dressings limit the pain in partial-thickness wounds to a greater degree than nonocclusive dressings.9 In an uncomplicated wound such as a donor site, occlusion may decrease the incidence of infection. The alginate fiber is produced as calcium alginate by extruding the aqueous solution of sodium alginate into a Ca2+ salt coagulating bath via the wet spinning process. The fiber is used in the production of dressings that interact with wound exudate to form a gel. Commercially available dressings are composed of alginate fibers that are generally carded and needlepunched to produce soft nonwoven dressings. They are also produced as ropes (ribbons) for deeper wound packing. Alginate dressing may be classified according to its absorbency into categories of either low absorbency or high absorbency: Dressings that absorb less than 6 g of liquid per g of fiber (or less than 12 g/100 cm2) are classified as dressings of low absorbency and dressings that absorb 6 g or more (or 12 g or more/100 cm2) are classified as dressings of high absorbency.10 Commercially available alginate dressings are generally a blend of calcium and sodium alginates. Different commercially available alginate dressings vary in their proportions of calcium and sodium alginates. Alginates are highly absorbent, hydrophilic and gel-forming materials. When a calcium alginate fibrous dressing absorbs sodium ions from a wound exudate, a gel is formed in situ, a moist environment is created at the wound site, and proportionate calcium ions are released from the dressing. Calcium ions, when released into wounds, stimulate both platelet activation and whole blood coagulation. This explains the hemostatic performance of alginate dressings.

Silver-based dressings Silver has been used as an antimicrobial agent for over 2000 years. The Romans and the Arabs placed silver coins in their water bags to keep their drinking water safe (fresh) for consumption.11 Silver nitrate has been used historically as an antiseptic agent. It was used in the Middle Ages along with cauterizing or burning with a hot iron to destroy dead or unwanted tissue to prevent the spread of infection. In the early 1800s, concentrations of 0.2% to 2% of silver nitrate were used on burn treatment, however, in the mid-1900s, 0.5% was used for burn treatment.12 Silver has a long modern history as an antimicrobial agent, especially in the treatment of chronic wounds and burns; this method was at one time a mainstay in the treatment of burns. Burn wounds, particularly those due to third and fourth degree burns, are highly susceptible to infection and scar formation. These complications can be

reduced if bacterial growth is inhibited and there is a moist but not overly wet wound environment that promotes healing without causing tissue maceration. Silver nitrate has a broad antibacterial spectrum and is effective against most bacterial strains especially Staphylococcus aureus, Staphylococcus epidermidis, and Klebsiella pneumoniae. Silver nitrate stains everything it touches to brown-black when exposed to light; the change in color does not affect its antimicrobial activity. By incorporating silver ions into alginate fibers, highly absorbent wound dressings with antimicrobial properties can be obtained. Dr. Yimin Qin13 reports that in clean wounds in pigs, the use of silver containing dressings increase the rate of epitheliazation by 28%, indicating a beneficial effect of silver ions in wounds, in addition to antimicrobial activity. The sustained slow release of low concentration of silver ions appears to stimulate healing. Besides using silver-coated fabrics for wound dressings, antimicrobial silver coatings are progressively being used for different finishing processes that impart functionalities as well as inhibit microorganisms, for example, in medical/health care, hygiene, bedding products, sports protective clothing, and personal care.14 Silver at the nano scale or silver-based nano particles provide high availability of bactericidal (and bacteriostatic) silver ions for improved antimicrobial effect. The silver ions in the silver alginate (Ag/ sodium/calcium alginate) dressing can enhance the dressing’s antimicrobial activities by the sustained release of silver ions.

Silver alginate and CM-printcloth dressings At the Southern Regional Research Center (SRRC), we have incorporated the antimicrobial properties of silver into commercially available alginates (and also silverCM cotton print cloth) in order to produce dressings that may be more efficacious in the treatment of exudative wounds. When alginate dressings are used on exudative wounds in the clinical setting, the recommended frequency of dressing changes is determined by the volume of the exudate. Product labels of the commercially available alginates recommend that the dressing can be left in place for up to one week, but may need to be changed more than once a day on highly exudative wounds. For clinical use, the silver dressings should retain the high absorptive ability of their alginate counterparts. Thus, this study describes an investigation on the absorption and swelling characteristics of the alginate/silver-alginates and of cottonCM-printcloth/silver-CM-printcloth in distilled water and 0.9% saline solution at eight hours and at one week (range of time commercially dressings are kept on wounds).

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It is worthwhile to summarize the salient features of our ongoing research on silver antimicrobials that has led to the present investigation of the measurement of the diameters of swollen silver antimicrobial dressings.12,15

Our earlier research findings Using a cation exchange technique, it was possible to impregnate commercially available alginate moist wound dressings and CM-cotton printcloth with silver.12,15,16 Silver-calcium-sodium-alginates, were developed in a two-step process from sterile calcium alginate dressings currently on the market, e.g., Kaltostat (ConvaTec), Curasorb (Kendall), Sorbsan (Maersk Medical), and AlgiSite M (Smith & Nephew). In the first step, each of these alginate dressings was treated with acetic acid in 80/20 to 90/10 ethanol/water for 45 minutes with fiber-to-liquor ratio of 1:10 to partially exchange the calcium ions with hydrogen ions. The dressings were subsequently treated wet-to-wet with silver nitrate to replace hydrogen ions with silver cations in 80/20 to 90/10 ethanol/water for 45 minutes to 12 hours at room temperature. A prolonged reaction of 12 hours with silver nitrate was preferred in the laboratory to allow (red-brown, brown-black) staining of the antimicrobial dressing visually confirming the presence of the silver cation; this is a qualitative test. The exact amount of silver cation on silver-alginates was determined.17 Silver-sodium-CM-printcloth was prepared from a low DS (degree of substitution ¼ 0.15) hygroscopic carboxymethylated cotton printcloth (CM-printcloth) in a two step aqueous process: first acidulation to partially replace sodium with hydrogen ions, and subsequently in the second step, replacing the hydrogen ions with silver ions by the treatment with silver nitrate. Low DS CM-cotton printcloth does not swell in water to the extent to get it dispersed in water as does the highly swelling high DS cotton (DS ¼ 0.31–4.0). Hence it does not call for non-aqueous media for cation exchange, as was the case in alginates.16 Only low DS CM-cotton printcloth was used in this study, however. The saline absorbency data of the four silver-alginate products (with their needle punched alginate controls), along with that of silver-CM-printcloth as an assessment of the dressings ability to function in a heavily exudating wound are reproduced in Table 1.17 The absorption determinations were carried out per Chakravarthy and British Pharmacopeia.18,19 The alginate dressings revealed different absorption capabilities. The saline absorbency assesses how well the presently developed silver-antimicrobials would function on exudating wounds; the silver-antimicrobials have the potential to function well when used on

Table 1. Absorption of saline fluid

Sample identification

Average of fluid absorbed (g/g)

Average of fluid absorbed (g/100 cm2)

Alginates needlepunched nonwovens Silver Algisite 12.82 Algisite (Control) 13.03 Silver Kaltostat 20.23 Kaltostat (Control) 24.99 Silver Curasorb 13.80 Curasorb (Control) 15.38 Silver Sorbsan 11.91 Sorbsan (Control) 12.50

20.18 21.19 14.47 24.72 24.70 20.91 20.79* 12.00

Cotton-CM-printcloth (low DS) Silver-CM-Printcloth 3.61 Printcloth (control) 3.93

6.15 4.05

*Silver Sorbsan shows higher absorption than that in Sorbsan (Control).

Table 2. Antimicrobial activity of Ag/Na-CM-cotton printcloth Organism count (CFU/mL) 24 hours

Percent reduction

Staphylococcus aureus Ag-CM-printcloth 1.8  105 Control (printcloth) 1.8  105

dry in Figures 1a–d; (b) Data from December 2003 to January 2004 (in 0.9% NaCl); (c) Data from December 2003 to January 2004 (in 0.9% NaCl); (d) Data from December 2003 to January 2004 (in 0.9% NaCl); (e) Data from December 2003 to January 2004 (in 0.9% NaCl). Note the swelling: 1wk > 8 hr > dry with decrease in fabric interstices (open area).

diameter of silver-alginate dressings and their alginate controls in water and in saline at 8 hours and at one week. All measurements are averages of the results from the four experimental runs, and are reported as a change in diameter in micrometers (mm). The increase in diameter is due to the absorption and swelling capabilities of the four alginate dressings. The percent change in diameter of the silver-alginate fibers at 8 hours of saline immersion was 166, 108, 59, and 162 for the silver-Sorbsan, silver-Kaltostat, silver-Curasorb, and silver-Algisite, respectively. The percent change in diameter after 1 week of immersion in saline for silver dressings was 153, 124, 54, and 176 respectively. The control alginate fibers and silver alginate fibers showed similar degrees of swelling. The relative fiber absorbency of Algisite, Kaltostat, and Sorbsan are similar;

whereas Curasorb is lower. Different dressings have different swellability and absorbency. The following observations can be made from the results. For control and silver-alginates there is a very significant increase in diameter of fibers in both saline and water, at 8 hours and at one week (p < 0.001 for one-way ANOVA). Most of the swelling in diameter occurs within the initial 8 hours of immersion, and continued immersion for a week produces only a modest further increase. In general, silver-alginates swelled less than their controls in either solution at 8 hours and at one week. For example, the Sorbsan control after 1 week of saline immersion had a 193% increase in diameter while the silver-Sorbsan swelled by only 153%. The greater swelling was observed with immersion in saline than in water for each of the dressings

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(c)

Curasorb dry

Curasorb wet 8 hour

Curasorb wet 1 week

SilverCurasorb dry

SilverCurasorb wet 8 hour

SilverCurasorb wet 1 week

Algisite M dry

Algisite M wet 8 hour

(d)

Algisite M wet 1 week

SilverAlgisite M dry

SilverAlgisite M wet 8 hour

SilverAlgisite M wet 1 week

CM-printcloth dry

CM-printcloth wet 8 hour

CM-printcloth wet 1 week

Silver-CM-printcloth dry

Silver-CM-printcloth wet 8 hour

Silver-CM-printcloth wet 1 week

(e)

Note the swelling: 1wk > 8 hr > dry with decrease in fabric interstices (open area).

Figure 1. Continued.

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Table 5. Percent change in fiber diameter of the dressings*

Controls Sorbsan Kaltostat Curasorb Algisite CM-Printcloth Silver Dressings Silver-Sorbsan Silver-Kaltostat Silver-Curasorb Silver-Algisite Silver-CM-Printcloth

Dry Diameter (mm)

8 hours water (%)

8 hours in NaCl (%)

1 week in water (%)

1 week in NaCl (%)

14.7 17.4 15.9 14.3 14.3

42 31 21 43 28

128 112 64 184 31

34 36 16 34 32

193 170 74 140** 21**

15.1 17.9 15.7 14.3 14.5

37 15 20 36 33

166 108 59 162 31

29 15 12 24 32

153** 124 54** 176 35

* derived from Table 4. ** data show lower figures than those in 8 hours.

suggests possible clinical utility. The data indicate that Sorbsan may be best suited for highly exudating wounds whereas Curasorb may be best applied on moderately/less exudating wounds. Nevertheless, the final result of wound healing that occurs during epithelialization may be very similar between the two silver treated dressings. The percent diameter change due to swelling in printcloth for 8 hours and one week in saline are shown in Tables 4 and 5. The swelling of printcloth is much lower than the swelling of alginates, as expected. And as with the alginates, printcloth swelled more in saline than in water and the majority of the swelling occurred during the first 8 hours of immersion. The silver printcloth swelled less than its control. Single fiber swelling of alginate dressings is illustrated in Figure 2, for the swelling of silver-Sorbsan alginate fiber in 0.9% NaCl solution. The general observation was that fluid absorption led to expansion in the diameter of the fiber but not in length (Figure 3). Six of the eight single fiber measurements showed a statistically significant expansion (swelling) in diameter (one-way ANOVA, p < 0.05); whereas length measurements showed no significant increase. With a small sample size of 1–2 mm and variability, the percent swelling (shown in Figure 3) could have been enhanced because more fluid could easily enter the cut fibers. Also the cut ends of the single fibers probably resulted in some fiber damage and may be responsible for differential swelling at fiber tips as shown in Figure 3. While the degree of swelling in individual fibers is probably not representative of intact fibers, the cut single fiber measurements clearly show that fibers swell in diameter, and not significantly in length.

Figure 2. Sorbsan silver rope: dry fiber above and same fiber after 6 minutes in 0.9% NaCl at room temp –measurement was made at 2:58 pm, initial measurement was made at 2:52 pm.

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450.0

6 Length

400.0

Width

Single fiber alginate swelling chart

350.0

6

Swelling (%)

300.0 250.0 200.0 3

6

150.0 100.0 50.0 0.0 –50.0

3

7

3

3 3

Curasorb RW Ag NaCI

3

6

Kaltostat RW Ag NaCI

6 7

6

Sorbsan Ag W Ag NaCI

6

6

Algisite Ag W Ag NaCI

Figure 3. Numbers represent sample size for each alginate fiber type and treatment. Legend: RW ¼ Regular alginate fiber (control) soaked in water; Ag NaCl ¼ Silver alginate fiber soaked in 0.9% NaCl; Ag W ¼ Silver alginate fiber soaked in water. Blue lines represent length of the fiber whereas red lines represent diameter.

Discussion Acute and chronic wounds such as those caused by burns or pressure ulcers generally produce a large amount of exudate, which impairs wound healing and provides a medium for bacterial growth. Such wounds are at high risk for getting infected. Efficient absorption of the wound exudate and the maintenance of a sterile (or near sterile) environment at the wound site is preferred. Alginate dressings have become the standard of care for treatment of these open, exudating wounds. These dressings have the ability to absorb significant amounts of the exudating fluid without desiccating the wound. The silver alginate dressings have additional antimicrobial properties imparted into them to improve their efficacy in wound healing by reducing the bacterial burden in the wound. Although this study reported effectiveness on Staphylococcus aureus and Klebsiella pneumoniae, it is possible that silver (I) alginate dressings may be effective on other bacterial or fungal strains. By demonstrating fiber swelling after immersion in water and saline, it was shown (in this study) that these antimicrobial dressings retain their absorptive qualities. Similar findings were reported for silver-CM-printcloth. However, the Ag-CM-cotton printcloth (less expensive) may be suitable for potential use against nosocomial acquired infections.17 It was also shown that the absorption of fluid leads to fiber swelling in diameter without increase in the length of the fibers. If used in vivo, when the exudate

is absorbed in the fiber structure of the needlepunched alginate dressings, the fibers may expand circumferentially upon swelling. As a result, the space between the fibers in the dressing is greatly reduced and the wound fluid is trapped not only in the fibers, but also between the swollen fibers. It is hypothesized that any bacteria from or around the wound are trapped, both within the fibers and in the space between the swollen fibers. With the change of dressings, these bacteria are removed from the wound site. Simultaneously, bacteria are killed at the wound site as the silver cations from the antimicrobial dressings are exchanged for sodium ions on the wound surface. Thus, infection is either prevented or eliminated. These properties may expand the clinical utility of the antimicrobial silver alginates beyond that of commercially available dressings. The fibrous swelling of silver alginates measured in this work was correlated with the absorption of saline fluid, (g of saline fluid per g of the dressing), as well as with the antimicrobial properties (against gram positive and gram negative microbes) of silver alginates of our earlier work. This study summarized that alginate dressings treated with ion-paired silver had robust antimicrobial activity while retaining the high absorption properties needed for medium to heavily exudating wounds.17

Summary The Ag-CM-cotton printcloth may be suitable for potential use against nosocomial acquired infections.

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Alginate dressings are versatile wound dressings because of their unique gel-forming properties and high absorption capabilities. They have gained widespread acceptance by the medical community. Although most work has been reported on the absorption of these dressings, very little information is available correlating the swelling of the fibers with the absorbency of the alginates, this study fills the gap. Silver alginate fibers swell and absorb wound fluids while limiting the infection by their bactericidal properties. Silver alginates have potential for developing into superior wound healing materials. Clinical trials with these dressings may help further elucidate the efficacy of the dressings.

Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Authors’ note Mention of trade names or commercial products in this article is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the US Department of Agriculture. References 1. Qin Y. Absorption characteristics of alginate wound dressings. J Appl Polym Sci 2004; 91(2): 953–957. 2. Winter GD. Formation of the scab and the rate of epithelization of superficial wounds in the skin of the young domestic pig. Nature 1962; 193(4812): 293–294. 3. Winter GD and Scales JT. Effect of air drying and dressings on the surface of a wound. Nature 1963; 197(4862): 91–92. 4. Bolton LL, Pirone L, Chen J and Lydon M. Dressings’ effects on wound healing. Wounds 1990; 2(4): 126–134. 5. Alvarez OM, Rozint J and Wiseman D. Moist environment for healing: matching the dressing to the wound. Wounds 1989; 1: 35–51. 6. Lionelli GT and Lawrence WT. Wound dressings. Surgical Clinics of North America 2003; 83(3): 617–638. 7. Linsky CB, Rovee DT and Dow T. Effects of dressings on wound inflammation and scar tissue. In: Dineen P and Hildick-Smith G (eds) The Surgical Wound, Philadelphia, PA, USA: Lea & Fibiger, 1981, pp.191–205.

8. Wiseman DM, Rovee DT and Alvarez O. Wound dressings: design and use. In: Cohen IK, Diegelmann RF and Lindblad WJ (eds) Wound Healing: Biochemical and Clinical Aspect, Philadelphia, PA, USA: W.B. Saunders Co., 1990, pp.562–580. 9. Barnett A, Berkowitz RL, Mills R and Vistnes LM. Comparison of synthetic adhesive moisture vapor permeable and fine mesh gauze dressings for split-thickness skin graft donor sites. American Journal of Surgery 1983; 145(3): 379–381. 10. Surgical Materials. British Pharmacopeia, 1993, Addendum 1995. 11. Holme I. Durable freshness through antimicrobial finishes. Textile Magazine 2004; 30(4): 14–16. 12. Parikh DV, Fink T, Rajasekharan K, Sachinvala ND, Sawhney APS, Calamari TA and Parikh AD. Antimicrobial silver/sodium carboxymethyl cotton dressings for burn wounds. Textile Res J 2005; 75(2): 134–138. 13. Qin Y. Silver Streak. Textile Horizons 2004; Nov/Dec: 16–17. 14. Tessier D. SilverClearÕ an outstanding silver technology. The Textile Journal 2008; Jan: 15–18. 15. Parikh DV, Sachinvala ND, Calamari TA and Negulescu I. Carboxymethylated cotton for moist wound healing. AATCC Review 2003; 3(6): 15–19. 16. Daul GC, Reinhardt RM and Reid JD. Studies on the partial carboxymethylation of cotton. Textile Res J 1952; 22(12): 787–792. 17. Parikh DV, Edwards JV, Condon BD and Parikh AD. Silver-carboxylate ion-paired alginate and carboxymethylated cotton with antimicrobial activity. AATCC Review 2008; 8(8): 38–43. 18. Chakravathy D, Fleck C and Falconio-West M. An evaluation of two polysaccharide-silver based high absorbency wound dressings. Presentation at the Symposium on Advanced Wound Care, San Antonio, TX, USA, April 2006. 19. British Pharmacopeia Monograph for Alginate Dressings and Packings, 1993, Addendum 1995 (Published on the recommendation of the Medicines Commission Pursuant to the Medicines Act 1968). 20. Joiner BG. Determining antimicrobial efficacy and biocompatibility of treated articles using standard test methods. In: Edwards JV and Vigo TL (eds) Bioactive Fibers and Polymers, ACS Symposium Series 792. Washington, D.C., USA: Oxford University Press, 2001, pp.201–217.

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