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Page 1: Principle Alginate Dressings

POLYMERS FOR ADVANCED TECHNOLOGIES

Polym. Adv. Technol. 2008; 19: 6–14

nce.wiley.com) DOI: 10.1002/pat.960

Published online 29 June 2007 in Wiley InterScience (www.interscie

The gel swelling properties of alginate fibers

and their applications in wound management

Yimin Qin*The Biochemical Materials Research and Development Center, Jiaxing College, Jiaxing 314001, Zhejiang Province, People’s Republic of China

Received 20 March 2007; Accepted 14 April 2007

*Correspoand DevZhejiangE-mail: yContract/vince, Ch

Calcium alginate fibers have a novel gel-forming capability in that, upon the ion exchange between

sodium ions in the contact solution and calcium ions in the fiber, the fiber slowly transforms into a

fibrous gel. This paper reviews the principles of the gel-forming process for alginate fibers and

analyzed the gelling behavior of various types of alginate fibers. The absorption characteristics of

alginate wound dressings were analyzed and it was found that alginate wound dressings absorb a

large quantity of liquid into the fiber structure, in addition to those held between the fibers in the

textile structure. This gives rise to the unique gel blocking properties of alginate wound dressings. In

addition, alginate wound dressings also have novel hemostatic and antimicrobial properties as well

as the ability to promote wound healing. They are now widely used in the management of highly

exuding wounds such as leg ulcers, pressure sores, and surgical wounds. Copyright # 2007 John

Wiley & Sons, Ltd.

KEYWORDS: alginate fiber; wound dressing; ion exchange; hydrogel; antimicrobial

INTRODUCTION

Alginate fibers are made from sodium alginate, which is a

natural polymer extracted from brown seaweeds. As a textile

fiber, alginate fiber has a limited use since it is relatively

expensive, and tends to dissolve in the alkali conditions of

many textile processes such as bleaching, dyeing, and

finishing. In the early stages of its development, alginate

fiber was used in the textile industry principally in the

production of water soluble yarns that would dissolve in a

scouring process.1,2 These yarns were used as a support

during the manufacture of fine lace, or as draw threads in the

production of hosiery. Fabrics from alginate fibers were once

produced commercially for their fire-resistant property,

because of the high content of metal ions in the fiber. Alginate

fibers were also used for themanufacture of bags used for the

transportation of soiled hospital linen that were designed to

dissolve in the wash. However, by the 1970s, they were

replaced for these applications by cheaper synthetic fibers.

Since the 1980s, alginate fibers have been widely used in

the manufacture of high-tech wound dressings.1–4 This can

be attributed to two reasons. First, it has been shown in recent

years that the ideal environment for wound healing is amoist

but not wet condition.5,6 In order to create this environment

on thewound surface, many productswere developedwith a

feature to hold moisture in its structure, so that the interface

between the wound surface and the dressing can be kept

ndence to: Y. Qin, The Biochemical Materials Researchelopment Center, Jiaxing College, Jiaxing 314001,Province, People’s Republic of [email protected] sponsor: Natural Science Fund of Zhejiang Pro-ina; contract/grant number: Y405030.

moist, and epithelial cells from the edge of the wound can

migrate across the wound surface. Second, alginate fibers

have a unique gel-forming characteristic whereby on contact

with wound exudates, the sodium ions in the wound

exudates can exchange with the calcium ions in the fiber, and

as more and more sodium ions enter the fiber structure, the

fiber absorbs more and more water and becomes a gel. For

the alginate wound dressings, as water enters the fiber

structure, the entire textile structure is transformed into a

sheet of moist gel, thus providing an ideal moist healing

environment for the wound. Many clinical trials have shown

that alginate wound dressings not only have the high

absorption capacities, but also the ability to promote wound

healing.7–16

This paper reviews the unique gel-forming properties of

alginate fibers and their application in the production of high

performance wound dressings.

THE PRINCIPLES OF GEL FORMATIONFOR ALGINATE FIBERS

As can be seen in Fig. 1, alginate is a linear polymeric acid

composed of 1,4-linked b-D-mannuronic acid (M) and

a-L-guluronic acid (G) residues. During the fiber making

process, sodium alginate is dissolved in water to form a

viscous solution, which is then extruded through spinneret

Copyright # 2007 John Wiley & Sons, Ltd.

Page 2: Principle Alginate Dressings

Figure 1. The chemical structure of alginic acid.

Table 1. The ion-exchange coefficients of alginate extracted

from two different types of seaweeds18

Metal ions

Type of seaweeds and the M/G ratio of alginate

Laminariadigitata, M/G¼ 1.60

Laminaria hyperboreastems, M/G¼ 0.45

Cu2þ–Naþ 230 340Ba2þ–Naþ 21 52Ca2þ–Naþ 7.5 20Co2þ–Naþ 3.5 4

Alginate fibers 7

holes into an aqueous calcium chloride bath, where upon the

ion exchange between calcium ions in the bath and sodium

ions in the as-spun filament, a swollen calcium alginate

filament is formed. Upon further stretching, washing, and

drying, calcium alginate fibers can be produced.

Figure 2 shows the structural changes during the

production and application of calcium alginate fibers as a

wound dressing material. During the production process,

sodium alginate is converted into calcium alginate when the

sodium alginate filament emerging from a spinneret is

coagulated by calcium ions in the calcium chloride solution.

On contact with wound fluid, which contains among other

components, sodium ions, the calcium ions in the calcium

alginate fiber exchange with the sodium ions, slowly

converting the fiber into sodium alginate. Since sodium

alginate is water soluble, water is drawn into the fiber,

turning it into a fibrous gel.17

The gel formation process depends on the formation of the

water soluble sodium alginate within the alginate fiber,

which is again dependent on the ability of sodium ions to

replace calcium ions in the fiber. In a study on the binding

abilities of alginate for divalent metal ions during the gel

formation of sodium alginate solution, Haug and Smidsrod18

had noted that the ability for alginate to bind divalent metal

ions is related to the ion-exchange coefficient between the

divalent metal ion and the sodium ion:

Figure 2. Structural changes during the production and

application of calcium alginate fibers as a wound dressing

material.

K¼ ½Metal ion concentration in the gel�½Sodi½Sodium ion concentration in the gel�2

Copyright # 2007 John Wiley & Sons, Ltd.

After studying various metal ions, Haug and Smidsrod18

found that the binding abilities for alginate are in the order

of:

Pb2þ > Cu2þ > Cd2þ > Ba2þ > Sr2þ > Ca2þ > Co2þ ¼ Ni2þ

¼ Zn2þ > Mn2þ

It should be pointed out that since they have significantly

different stereochemical structures, guluronic acid and

mannuronic acid have significantly different binding abil-

ities to metal ions. Table 1 shows the ion-exchange

coefficients of alginate extracted from two different types

of seaweeds.18 It can be seen that the ion-exchange

coefficients differ greatly both in terms of the different metal

ions against the same variety of alginate, and also for the

same metal ions against alginate with different guluronic

acid andmannuronic acid contents. For the calcium alginate,

the ion-exchange coefficients between calcium and sodium

are 7.5 and 20, respectively for the alginate with high M and

high G contents.

It is clear that among differentmetal ions, calcium ion has a

relatively weak binding with alginate. The choice of calcium

as the divalent metal ion used for the production of alginate

um ion concentration in the solution�2

½Metal ion concentration in solution�

fibers for woundmanagement is therefore a right choice from

the point of view of the subsequent gelation of the fiber when

it is in contact with wound exudate. Should other metal ions

such as barium are used, the absorption and gel-forming

abilities of the alginate wound dressings would be poorer.

The differences in the ion-exchange coefficients also

explain the differences in the gel-forming abilities of the

high M and high G calcium alginate fibers. As can be seen in

Figs. 3 and 4, when a high G calcium alginate fiber is placed

in contact with normal saline solution, because the calcium

ions bind firmly with alginate, ion-exchange is difficult, and

the fiber swelling is limited. On the other hand, for the high

M calcium alginate fiber, because the binding between

calcium ion and the alginate is relatively weak, ion exchange

between calcium ions in the fiber and sodium ions in the

solution is easy, hence the fiber quickly turns into a mixed

calcium and sodium alginate when in contact with normal

saline solution. A fibrous gel is formed as a result.

It is important to point out that body fluid has a complex

composition and in addition to the ion exchange between

Polym. Adv. Technol. 2008; 19: 6–14

DOI: 10.1002/pat

Page 3: Principle Alginate Dressings

Figure 3. Photomicrographs showing the swelling of high G

calcium alginate fiber when wet in normal saline, 200�.

Figure 4. Photomicrographs showing the swelling of high M

calcium alginate fiber when wet in normal saline, 200�.

8 Y. Qin

sodium and calcium ions, the protein component in the

wound exudate can also bind calcium ions, hence increasing

the gel-forming abilities of the calcium alginate fibers. In a

study of the composition of serous fluid formed after axillary

dissection, Bonnema et al.19 found that on the first post-

operative day, the drainage fluid contained blood contents

and a high concentration of creatine phosphokinase. After

day one, it changed to a peripheral lymph-like fluid that

Table 2. The calcium release and gel swelling properties of three

Ratio of M/G

High G fiber

About 0.4

Ca(II) content in contact solution, ppm 317.5Gel swelling ratio in water, g/g 2.69� 0.27Gel swelling ratio in 0.9% saline, g/g 8.49� 0.62

Copyright # 2007 John Wiley & Sons, Ltd.

contained different cells and more protein. Frohm et al.20

analyzes the fluid from a post-operative wound, six leg

ulcers, and a large blister. They found that wound fluid con-

tains fragments of peptides. Trengrove et al.21 found thatwound

fluid collected from leg ulcers contained 0.6–5.9mmol l�1

glucose and 26–51 g l�1 protein. James and Taylor22 showed

that a typical wound fluid contained 2.9% protein.

THE GELLING ABILITIES OF ALGINATEFIBERS

Table 2 shows the gelling abilities of three types of alginate

fibers with different M/G contents. The high G alginate fiber

contains about 70% G and 30% M acids, while the high M

alginate has about 65% M and 35% G acids. After being in

contact with solution A (defined in the British Pharmacopeia

as an aqueous solution containing 142mmol of sodium

chloride and 2.5mmol of calcium chloride) for 30min at

378C, the solution of the high G alginate fiber contains about

317.5 ppm calcium ions, while the solution of the high M

alginate fiber contains 560ppm calcium ions, almost twice as

much as the figure for the high G alginate fiber. This clearly

demonstrates that the high M alginate fiber exchanges ions

more readily with the sodium-containing solution, and its

gelling ability is much better than the high G alginate fiber.17

Figure 5 shows the photomicrographs of a piece of high G

calcium alginate fiber whenwet in water.23 It can be seen that

apart from a slight degree of swelling, the fiber showed a

minimum level of change before and after wetting. This is

understandable as in a high G calcium alginate fiber, the

polymeric chains are firmly bound together through the ‘egg

boxes’ formed between GG blocks in neighboring polymer

chains. It is difficult for water to penetrate into the firm

polymer structure, hence the fiber has a good wet stability.

Figure 6 shows the photomicrographs of a piece of high M

calcium alginate fiber when wet in normal saline solution. It

is clear that the wet sample has absorbed a large amount of

water into the fiber structure during the wetting process,

effectively turning itself into a piece of hydrogel. In clinical

applications, when high M alginate fibers are placed in

contact with wound exudate, the exchange of sodium and

calcium ions gradually transforms calcium alginate fiber into

sodium alginate fiber, resulting in the formation of a fibrous

gel, and in the process, the absorption of a large quantities of

exudate by the dressing.

The gel swelling abilities of the alginate fibers can be

measured quantitatively by placing 0.2 g of fiber in 100ml of

either distilled water, or 0.9%wt/wt aqueous sodium

chloride solution (normal saline). After 1 hr, the fibers are

separated with the contacting solution and placed in a

centrifuge tube with the bottom half filled with knitted

types of alginate fibers17

Mid-G fiber High M fiber

About 1.6 About 1.8

450 5606.0� 0.87 5.69� 0.3914.51� 0.74 15.89� 0.65

Polym. Adv. Technol. 2008; 19: 6–14

DOI: 10.1002/pat

Page 4: Principle Alginate Dressings

Figure 5. Photomicrographs of a piece of high G calcium

alginate fiber when wet in water, 200�.

Figure 6. Photomicrographs of a piece of high M calcium

alginate fiber when wet in normal saline solution, 200�.

Alginate fibers 9

viscose rayon fabric to contain the spin off solution. The

centrifuge is carried out at 1200 rev/min for 15min. After

that the fiber (W1) is dried at 1058C to constant weight (W2).

The gel swelling ratio is expressed as the ratio between the

weight of the wet sample and that of the dry sample, i.e.,W1/

W2.24

As can be seen in Table 2, when wet in water, high G

calcium alginate fiber had a limited extent of swelling, with

the gel swelling ratio of 2.69, similar to the value obtained

from cotton and viscose rayon fibers. High M alginate fibers

swell better than high G alginate fibers, however, this

Table 3. The gel swelling properties of three types of alginate fib

Sample High calcium fiber

Calcium alginate content 98.3%Sodium alginate content 1.7%Gel swelling ratio in water, g/g 2.69� 0.27Gel swelling ratio 0.9% saline, g/g 8.49� 0.62

Copyright # 2007 John Wiley & Sons, Ltd.

difference widens when saline is used as the contacting

media. The gel swelling ratio for a high M calcium alginate

fiber in saline is 15.89, as compared to that of 8.49 for a high G

calcium alginate fiber.

Since sodium alginate is responsible for the swelling of

alginate fibers in aqueous media, during the production

process, calcium alginate fibers were converted into a mixed

calcium and sodium alginate in order to make the product

more absorbent. It can be seen from Table 3 that as the

contents of sodium ions increase, there is a corresponding

increase in the absorption capacities of the dressings. The gel

swelling ratio in 0.9% saline increased from 8.49 g/g for the

high calcium fiber to 18.58 g/g for the high sodiumfiber. This

result suggests that oneway of improving the absorption and

gelling properties of the alginate wound dressing is to

introduce sodium ions into the fiber.

THE GEL BLOCKING PROPERTIES OFALGINATE WOUND DRESSINGS

Figure 7 shows the nonwoven structure of a piece of calcium

alginate wound dressing. When the dressing is in contact

with wound exudate, absorption takes place in two ways.

First, some of the wound fluid is held by capillary forces

between the fibers in the nonwoven textile structure. This

action is rapid and the liquid is held by physical forces.

Second, as the fibers are wet, water is drawn into the fiber

structure by chemical forces. In the case of alginate wound

dressings, a large amount of water is absorbed into the fiber

structure as the fiber transforms into a mixed salt of calcium

and sodium alginate.

In view of the above analysis, the absorption of liquid by a

wound dressing can be divided into three categories, i.e. the

overall absorption of the dressing, liquid absorbed between

the fibers, and liquid absorbed into the fiber. In order to

quantify these three forms of absorption capacity, samples of

alginate dressings are cut into 5 cm� 5 cm sizes and

conditioned at 208C, 65% relative humidity overnight. The

dressings are thenweighed (W) before being placed in plastic

Petri dishes (90mm in diameter) and wetted with 40 times

their own weight of solution A. The dish is then placed in a

378C oven for 30min. After that, the dressing is lifted out of

the solution by holding it with a forcep at one corner. The

solution is left to drip for 30 sec and the wet dressing is

weighed (W1). The sample is then placed in a centrifuge tube

half filled with knitted gauze to contain the spin-off liquid.

After centrifuging at 1200 rpm for 15min, the dressing is

taken out and weighed again (W2). Finally, the dressing

is dried to a constant weight at 1058C for 4 hr and the weight

is weighed (W3).24

ers containing different levels of sodium ions17

Mid-calcium fiber High sodium fiber

76.5% 54.1%23.5% 45.9%

24.05� 0.85 20.60� 2.6613.42� 1.03 18.58� 0.94

Polym. Adv. Technol. 2008; 19: 6–14

DOI: 10.1002/pat

Page 5: Principle Alginate Dressings

Figure 7. The nonwoven structure of a piece of calcium

alginate wound dressing.

Figure 8. Photomicrograph of a piece of alginate nonwoven

dressing wet in normal saline, 200�.

10 Y. Qin

In the above mentioned experiment (W1�W)/W

represents the standard absorption capacity of a dressing

defined in the British Pharmacopeia for alginate wound

dressings. (W1�W2) represents the liquid held between the

fibers, while (W2�W3) represents that held inside the fiber.

When the fiber is highly hydrophobic, such as glass fibers,

the absorption of fluid would be held mainly between fibers

by capillary forces. On the other hand, in the case of some

superabsorbent fibers, most of the absorption takes place

inside the fibers.

Table 4 shows the absorption behavior of two types of

alginate dressings and other non-alginate materials. Because

of the ion-exchange properties, alginate fibers absorb much

more liquid into the fibers than other non-alginate dressings.

It should be pointed out that in the case of a wound dressing,

the fact that fluid can be absorbed into the fiber structure is

important in several respects. First, when the fluid is

absorbed into the fibers, they swell as a result. As the fiber

expands upon swelling, the free spaces between the fibers are

closed, and bacteria in the textile structure or in the wound

exudates are then immobilized. This can help prevent the

proliferation of bacteria, and reduce wound infection and

cross infection in hospital wards. Second, if the fluid is held

between the fibers by capillary forces, it can easily migrate

along the textile structure. Clinically, this would mean the

spreading of wound exudates from the wounded area to the

surrounding healthy skins under the dressing, causing skin

maceration. Ideally, wound dressings should be able to

absorb a large amount of exudates, and contain the fluid

within the fiber structure.

Figure 8 shows the photomicrograph of a piece of alginate

nonwoven dressingwet in normal saline. Compared to Fig. 7,

it can be seen that the fibers within the dressing are highly

swollen, blocking the capillary structure, hence limiting the

Table 4. Absorption behavior of two types of commercial alginate

Product (W1�W)/W (W1�W

SorbsanTM 11.98 73.7KaltostatTM 16.30 47.1Knitted fabric of viscose filament yarn 1.88 4.6Woven cotton gauze 4.83 11.5Polyester nonwoven fabric 18.35 67.6

Copyright # 2007 John Wiley & Sons, Ltd.

lateral spreading of the liquid. This so-called ‘gel blocking’

property is clinically an important feature of an alginate

wound dressing. As Fig. 9 clearly shows, wound covered by

an alginatewound dressing has a clean edge,with thewound

exudate absorbed into the dressings immediately on top of

the wound surface.

ALGINATE WOUND DRESSINGS

Alginate has a long history of applications in wound

management. It is reported that early sailors used seaweeds

to treat wounds, burns and eczema, and during the World

Wars, because of shortage of cotton, dried seamoss dressings

were sent to field hospitals to treat wounded soldiers.9

DuringWorldWar II, Blaine25 investigated tissue reactions to

alginate fibers and reported the use of alginate fibers for

hemostasis and as a bone wax substitute.26 In 1951, Blaine

used alginate fibers as absorbable hemostats in surgery and

noted that 10 days after the implantation, the alginate became

almost entirely absorbed. Blaine27 also reported that

alginates did not lessen the antibiotic activity, could be heat

sterilized, and did not promote bacterial growth.

The first modern alginate wound dressing was brand

named Sorbsan, whichwas launched in 1983.28 It consisted of

a loose fibrous fleece made from calcium alginate fibers with

a high mannuronic acid content. This was followed by other

products that differed both in their chemical composition

and textile structures. For example, Kaltostat, a fibrous high

G calcium alginate, was introduced into the market in 1986.

Later, Kaltostat was further modified to consist of a mixture

of calcium and sodium alginate. The sodium alginate was

introduced to improve the gel-forming ability of the fibers.

Alginate wound dressings are produced either as flat

sheets, which are used to cover superficial wounds, or as

and some non-alginate wound dressings24

2)/W3 (W2�W3)/W3 (W1�W2)/(W2�W3) W3

15.2 4.83 0.13914.8 3.18 0.198

4 2.72 1.71 0.3796.45 1.78 0.0593.97 17.01 0.494

Polym. Adv. Technol. 2008; 19: 6–14

DOI: 10.1002/pat

Page 6: Principle Alginate Dressings

Figure 9. A leg wound covered by a piece of alginate wound

dressing.

Alginate fibers 11

cavity fillers, usually in the form of ribbon or rope. The flat

dressings are normallymade in a nonwoven fabric process in

which the fibers are carded to form a web that is then

cross-lapped to form a felt. In some products, the felt is then

needled or entangled by means of high-pressure water jets to

give the dressing a coherent structure.1

After more than two decades of development, alginate

wound dressings have now become one of the most versatile

wound dressing materials. They have unique gel-forming

properties and high absorption capacities. It is now generally

accepted that the wound heals better in a moist condition,

and the ability to form a moist gel has given the alginate

dressings their unique characteristics. They are gaining

widespread use in the management of exuding wounds such

as pressure sores and leg ulcers.

Table 5 outlines the key structural features for several

types of commercial alginate wound dressings. It is

important to point out that for an alginate wound dressing,

there are three structural levels to differentiate different

products, i.e. molecular, fibrous, and textile structures.

Alginate is a copolymer and its molecules differ on the

relative proportions of a-L-guluronic acid and b-D-mannuronic

acid monomers. During the wet spinning process, sodium

alginate is converted into calcium alginate. In some cases,

part of the alginic acid in the fiber can form salt with sodium

ions, resulting in a mixture of calcium/sodium alginate.

Different fibers can differ in the metal ion composition as

well as the various types of additives that are blended into

the fiber during the production process, for example, CMC is

added into the fiber to increase the absorption capacity.

During the production process for wound dressings, the

Table 5. Key structural features of seven commercially available

Ratio between guluronateand mannuronate contents

SorbsanTM �39/61TegagelTM �39/61AlgosterilTM �68/32KaltostatTM �68/32Tegagen HGTM �38/62CurasorbTM �68/32UrgosorbTM

Alginate/CMC ratio� 85/15 �68/32

Copyright # 2007 John Wiley & Sons, Ltd.

carding and needling process also differ for different

products, for example, Sorbsan is presented as a loose

unneedled fleece, while Kaltostat is presented as a needle

punched integral felt.29

PROPERTIES AND APPLICATIONS OFALGINATE WOUND DRESSINGS

The hemostatic properties of alginate wounddressingsIn 1951 Blaine27 performed a comparative evaluation of

absorbable hemostatic agents, including alginates. He found

that after 12 weeks, calcium alginate fibers were absorbed in

the body, while sodium alginates were generally absorbed

within 10 days. Blair et al.30 compared the hemostatic effect of

oxidized cellulose (Surgicel), porcine collagen (Medistat),

calcium alginate (Kaltostat), and surgical gauze in liver

lacerations in the rabbit. Their results showed that calcium

alginate stopped bleeding in less than 3min comparedwith a

mean of 5.7� 0.75min for porcine collagen, 12.5� 0.9min for

oxidized cellulose, and >15min with gauze.

Sirimanna31 investigated the use of calcium alginate fiber

for packing nasal cavity following surgical trimming of the

inferior turbinates. Thirty-two nostrils were packed with

Kaltostat for 36–48 hr to achieve hemostasis. There was no

bleeding while the packs were in place or after removal.

These results were compared retrospectively with two other

treatments, i.e. trousered paraffin gauze and glove finger

packs, both of which had been associated with bleeding in

over 50% of cases either while in situ or after removal. In a

second study, the three types of packings were compared

prospectively.32 All three were similarly effective in

preventing bleeding while in situ, but the alginate caused

significantly less bleeding on removal.

The hemostatic effect of the alginate fibers was attributed

to the calcium ions released from the fibers, which can

activate platelet coagulation. In this respect, products made

from high M alginates are more effective than their high G

equivalent. Evidence for the hemostatic activity of one high

M alginate dressing, Sorbsan, was produced in a study in

which the dressing was applied to experimental, full, and

partial thickness woundmodels for up to 14 days to assess its

effects on healing. Histological evaluation showed the

dressing to be an effective hemostat, generally well tolerated

by body tissues.33

In a detailed study on the hemostatic properties of various

alginate wound dressings, it was shown that high M type

dressings generally have better hemostatic properties than

alginate wound dressings29

Ratio between calciumand sodium content

Nonwovenstructure

�96.6/3.4 Unneedled�96.6/3.4 Hydro-entangled�99.6/0.4 Needled�80/20 Needled�65/35 Needled�99.2/0.8 Needled

�95.2/4.8 Needled

Polym. Adv. Technol. 2008; 19: 6–14

DOI: 10.1002/pat

Page 7: Principle Alginate Dressings

Figure 11. The antimicrobial action of silver containing algi-

nate fibers against E. Coli.

12 Y. Qin

high G alginate dressings. In addition, after comparing the

effects of calcium and zinc containing alginates and

non-alginate dressings on blood coagulation and platelet

activation, it was found that alginate materials activated

coagulation more than non-alginate materials, with zinc

alginate being more effective than calcium alginate.34

The antimicrobial functions of alginatewound dressingsFor alginate fibers, it is well known that when they are in

contact with wound exudate, the calcium ions in the fibers

exchange with sodium ions in the fluid, and the fibers are

transformed from water insoluble calcium alginate into

water soluble sodium alginate, resulting in the absorption of

a large amount of water by the fibers. In a wound dressing,

typically with a nonwoven structure, as the fibers absorb

water and swell, the spaces between the fibers are closed and

any bacteria that are carried in the wound exudate are

trapped in the wound dressing. This can help reduce the

spreading of bacteria, giving the alginate wound dressings

bacteria static properties.35

The development of silver containing alginate fibers has

enhanced the antimicrobial activities of alginate wound

dressings by the sustained release of the broad spectrum

antimicrobial silver ions.36 Figure 10 shows the antimicrobial

mechanism for the silver containing alginate wound

dressings. As the dressing absorbs exudates, the fibers

absorb liquid into the fiber structure and swell as a result,

reducing the interfiber spaces and effectively trap bacteria in

the nonwoven structure. The release of silver ions from the

fibers then kills the bacteria that are trapped in the alginate

wound dressing, thus making the dressings highly anti-

microbial.

Figure 11 shows the antimicrobial action of silver

containing alginate fibers against Escherichia Coli. There

was 100% reduction in bacteria count within 5 hr after the

fibers were placed in contact with solutions containing the

bacteria. Interestingly, although the Sorbsan alginate fibers

showed some antimicrobial activity, in the solution contain-

ing the other alginate fiber and AquacelTM (made of

carboxymethyl cellulose), antimicrobial effect was not noted

Figure 10. The antimicrobial mechanism of the silver con-

taining alginate wound dressings.

Copyright # 2007 John Wiley & Sons, Ltd.

and there was increased rate of bacteria growth in some

cases.

The wound healing properties of alginatewound dressingsOn contact with wound, alginate wound dressings can

stimulate macrophage activities. The interaction between the

alginate molecule and macrophage cells plays a key role in

many physiological and pathophysiological processes

during the wound healing process by synthesizing various

biologically active molecules called cytokines. Tumor

necrosis factor-a (TNF-a) is an important cytokine, having

cytotoxic properties against both tumor cells and normal

cells infected with intracellular pathogens. It is also a very

important inflammatory mediator, which modulates many

physiological and immunological functions and has been

implicated in inflammatory conditions. Otterlei et al.37

compared the ability of different alginates to stimulate

macrophage cells to produce TNF-a, interleukin-1, and

interleukin-6. They reported that high M alginates were

approximately 10 times more potent in inducing cytokine

production than high G alginates and therefore proposed

that mannuronic acid residues are the active cytoki-

ne-inducers in alginates. Other authors have also produced

evidence to suggest that it is MM blocks rather than GG that

is responsible for cytokine stimulation and antitumor

activity. A treatment of high M alginate with C-5 epimerase,

which converts b-D-mannuronic acid into a-L-guluronic acid,

results in a loss of TNF-inducing ability.38

In another study, it was found that a low concentration of

an extract of an alginate dressing stimulated human

fibroblasts on extended contact,13 indicating that alginate

wound dressings can promote wound healing.

Clinical uses of alginate wound dressingsThe first person in modern times to recognize the potential

value of alginate in surgery and wound management was

George Blaine, a major in the Royal ArmyMedical Corps. He

showed them to be absorbable in tissue, sterilizable by heat,

and compatible with penicillin.39 He also described how he

had used alginate films clotted in situ for the treatment of

wounds and burns in troop ship hospitals in the Far East and

described the use of alginate, sometimes in combination with

plasma as an alginate–plasma film, as ‘puncture patches’

over scleral defects.

During a subsequent assessment of the use of alginate as

hemostats and wound dressings, Blaine25 reported the

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Alginate fibers 13

apparent lack of toxicity following a series of animal studies

in which fibers were implanted into animal tissues, and gels

made from alginates were used to treat experimentally

produced burns. Successful use of alginate-derivedmaterials

in aural surgery and neurosurgery was reported by Passe

and Blaine40 and Oliver and Blaine,26 respectively. Bray

et al.41 described the results of a 3-month trial on the use of

alginate in the casualty department of Croydon Hospital.

Alginates in the form of films, wool, gauzes, and clots formed

in situ by mixing sterile solutions of calcium chloride and

sodium alginate, were applied to a wide range of wounds,

including burns, lacerations, ulcers, and amputations. In all

cases, healing was rapid and uneventful. By the late 1940s

and early 1950s, alginates were being used in some 70

hospitals in the UK over a range of surgical specialties.27

More recently, the first clinical report regarding a fibrous

alginate wound dressing was published in 1983 when Fraser

and Gilchrist8 and Gilchrist and Martin42 described their

experiences with the Sorbsan alginate dressing in the

management of foot disorders and a variety of skin lesions,

following a clinical evaluation in a group of hospitals in the

Sunderland area. The results of these studies were very

positive and supported the findings of Blaine some 40 years

earlier. Further papers described the use of Sorbsan in the

management of problem wounds including infected trau-

matic wounds and leg ulcers.43,44

Alginate wound dressings are used on many types of

wounds with medium to high levels of exudates. Some of

these wounds are described below.

Leg ulcersThomas and Tucker carried out a controlled trial of an

alginate dressing involving 64 community patients with leg

ulcers.45 The patients were allocated to treatment with either

an alginate dressing (Sorbsan) or paraffin gauze (tulle) as a

control. Only 4% of the ulcers treated with tulle healed

during the study, while 31% of those treatedwith the alginate

healed completely. The average healing rate achieved with

the alginate was over four times of that with tulle. Overall,

73% of alginate patients showed improvement during the

trial, compared with 43% in the control group.

Burns and donor sitesAlginate wound dressings are ideal for the treatment of

burns and donor sites, where their hemostatic and absorbent

properties are most useful. Groves and Lawrence10 com-

pared Sorbsanwith a standard gauze pad. In a laboratory test

the alginate absorbed nearly three times as much citrated

blood as the gauze; when applied to fresh, split-thickness

donor sites for 5min after excision, blood loss from the sites

treated with the alginate was almost half than from those

treated with gauze.

The effect of long-term application of alginates to donor

sites was investigated by Attwood.11 In an initial study, 15

patients with split skin grafts had half of their wound

dressed with an alginate (Kaltostat), and the other with

paraffin gauze. Every area dressed with the alginate showed

significantly better healing than the corresponding ‘control’

area. The second phase of the study assessed the time to

complete healing of alginate-dressed areas and patient

Copyright # 2007 John Wiley & Sons, Ltd.

acceptability of the dressing. A total of 155 donor sites were

examined, among these, 130 were treated with alginate and

25 with paraffin gauze. Sites treated with the alginate healed

in 7.0� 0.71 days, whilst the paraffin gauze dressed wounds

took an average time of 10.75� 1.6 days to heal. Patient

comfort and the quality of healing with the alginate were

significantly better than that achieved with gauze.

Pressure ulcersSayag et al.12 compared the efficacy of an alginate (Algosteril)

with that of dextranomer paste, an established local

treatment, in a prospective, randomized, controlled trial of

92 patients with full-thickness pressure ulcers. A minimum

40% reduction inwound areawas obtained in 74% of patients

in the alginate group and 42% in the dextranomer group. The

median time to achieve this reduction was 4 weeks for the

alginate and more than 8 weeks for the dextranomer. Mean

surface area reduction per week was 2.39� 3.54 cm2 and

0.27� 3.21 cm2 in the alginate and dextranomer groups,

respectively. The authors concluded that the striking efficacy

of the alginate dressings suggested that they may have

pharmacological properties to wound healing.

NOVEL USES OF THE GEL-FORMINGABILITIES OF ALGINATE FIBERS

In addition to nonwoven wound dressings, alginate fibers

can be used to make a number of novel composite materials

for wound management and other biomedical applications.

Qin and Gilding made fiber reinforced alginate gel by

dispersing chopped calcium alginate fibers in a solution of

sodium alginate. During drying, the calcium ions released

from the alginate fibers crosslinked the sodium alginate, and

a fiber reinforced sheet of alginate was formed. When in

contact with water, the sodium alginate component in the gel

absorbs water into the sheet and a hydrogel is formed. If the

mixture of calcium alginate fiber and sodium alginate

solution is placed in a freezer to form a sheet of solid ice,

and then taken immediately to a freeze drying machine, a

freeze-dried pad can be prepared over a period of about

20 hr. The resultant product is a porous dehydrated hydrogel

capable of absorbing more than 20 g of normal saline for a

gram of the sheet material.46

In order to donate moisture to dry wounds, the calcium

alginate fibers can be mixed with sodium alginate solution to

form amorphous hydrogels.47,48 By mixing 1 kg of calcium

alginate fibers with a length of about 10mm, 1.2 kg of sodium

alginate and 50 g of sodium citrate in 40 l of water and 8.5 kg

of propylene glycol, a viscous fibrous gel can be formed, with

a viscosity of about 800,000mPa s. This type of gel can be

applied on dry wounds to donate water to the devitalized

tissue, allowing them to separate from the wound, so that a

clean wound surface can be developed.

It is also possible to produce sheet hydrogel by impre-

ganating a nonwoven alginate felt with a sodium alginate

solution.49 For example, a nonwoven calcium alginate felt

with a weight/unit area of about 60 gm�2 was treated with a

2% sodium alginate solution dissolved in a 80/20 mixture of

water and propylene glycol, with the ratio between solution

to felt at 40 to 1. The fibers in the nonwoven felt interacted

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Page 9: Principle Alginate Dressings

14 Y. Qin

with the sodium alginate in the solution to form a sheet

hydrogel. The resultant gel could be autoclaved to provide a

hydrated sheet hydrogel for the treatment of superficial

wounds with low to medium level of exudate.

Renn et al.50 developed a method of producing an

absorbent foam material from calcium alginate fibers and

sodium alginate solution. They dispersed surfactants in the

sodium alginate solution to create a foamy mixture. When

short calcium alginate fibers are mixed into this foam, the

calcium ions released from the fibers crosslink the sodium

alginate, and the foam structure is immobilized. After

drying, a porous alginate foam can be produced.

SUMMARY

Because of the ion exchange between the calcium ions in the

fiber and sodium ions in the wound exudate, alginate fibers

can form gel when applied to exuding wounds. The gelling

process is accompanied by the absorption of wound exudate

into the fiber structure and as the fibers swell, the capillary

structure in the nonwovenwound dressing is closed, thereby

blocking the lateral spreading of liquid. This unique ‘gel

blocking’ property of alginate wound dressings helps reduce

wound maceration. In addition, since alginate wound

dressings have novel hemostatic and antimicrobial proper-

ties, especially with the addition of silver ions, they are

ideally suited for the management of chronic wounds where

a high level of exudates is common.

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