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POLYMERS FOR ADVANCED TECHNOLOGIES

Polym. Adv. Technol. 2008; 19: 6–14


Published online 29 June 2007 in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/pat.960

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

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 moist, and epithelial cells from the edge of the wound can
migrate across the wound surface. Second, alginate fibers
Alginate fibers are made from sodium alginate, which is a have a unique gel-forming characteristic whereby on contact
natural polymer extracted from brown seaweeds. As a textile with wound exudates, the sodium ions in the wound
fiber, alginate fiber has a limited use since it is relatively exudates can exchange with the calcium ions in the fiber, and
expensive, and tends to dissolve in the alkali conditions of as more and more sodium ions enter the fiber structure, the
many textile processes such as bleaching, dyeing, and fiber absorbs more and more water and becomes a gel. For
finishing. In the early stages of its development, alginate the alginate wound dressings, as water enters the fiber
fiber was used in the textile industry principally in the structure, the entire textile structure is transformed into a
production of water soluble yarns that would dissolve in a sheet of moist gel, thus providing an ideal moist healing
scouring process.1,2 These yarns were used as a support environment for the wound. Many clinical trials have shown
during the manufacture of fine lace, or as draw threads in the that alginate wound dressings not only have the high
production of hosiery. Fabrics from alginate fibers were once absorption capacities, but also the ability to promote wound
produced commercially for their fire-resistant property, healing.7–16
because of the high content of metal ions in the fiber. Alginate This paper reviews the unique gel-forming properties of
fibers were also used for the manufacture of bags used for the alginate fibers and their application in the production of high
transportation of soiled hospital linen that were designed to performance wound dressings.
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 PRINCIPLES OF GEL FORMATION
the manufacture of high-tech wound dressings.1–4 This can FOR ALGINATE FIBERS
be attributed to two reasons. First, it has been shown in recent
years that the ideal environment for wound healing is a moist As can be seen in Fig. 1, alginate is a linear polymeric acid
but not wet condition.5,6 In order to create this environment composed of 1,4-linked b-D-mannuronic acid (M) and
on the wound surface, many products were developed with a a-L-guluronic acid (G) residues. During the fiber making
feature to hold moisture in its structure, so that the interface process, sodium alginate is dissolved in water to form a
between the wound surface and the dressing can be kept viscous solution, which is then extruded through spinneret

*Correspondence to: Y. Qin, The Biochemical Materials Research


and Development Center, Jiaxing College, Jiaxing 314001,
Zhejiang Province, People’s Republic of China.
E-mail: yiminqin1965@126.com
Contract/grant sponsor: Natural Science Fund of Zhejiang Pro-
vince, China; contract/grant number: Y405030.

Copyright # 2007 John Wiley & Sons, Ltd.


Alginate fibers 7

Table 1. The ion-exchange coefficients of alginate extracted


from two different types of seaweeds18
Type of seaweeds and the M/G ratio of alginate

Laminaria Laminaria hyperborea


Metal ions digitata, M/G ¼ 1.60 stems, M/G ¼ 0.45
Figure 1. The chemical structure of alginic acid.
Cu2þ–Naþ 230 340
Ba2þ–Naþ 21 52
Ca2þ–Naþ 7.5 20
holes into an aqueous calcium chloride bath, where upon the Co2þ–Naþ 3.5 4
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 After studying various metal ions, Haug and Smidsrod18
drying, calcium alginate fibers can be produced. found that the binding abilities for alginate are in the order
Figure 2 shows the structural changes during the of:
production and application of calcium alginate fibers as a
wound dressing material. During the production process, Pb2þ > Cu2þ > Cd2þ > Ba2þ > Sr2þ > Ca2þ > Co2þ ¼ Ni2þ
sodium alginate is converted into calcium alginate when the ¼ Zn2þ > Mn2þ
sodium alginate filament emerging from a spinneret is
coagulated by calcium ions in the calcium chloride solution. It should be pointed out that since they have significantly
On contact with wound fluid, which contains among other different stereochemical structures, guluronic acid and
components, sodium ions, the calcium ions in the calcium mannuronic acid have significantly different binding abil-
alginate fiber exchange with the sodium ions, slowly ities to metal ions. Table 1 shows the ion-exchange
converting the fiber into sodium alginate. Since sodium coefficients of alginate extracted from two different types
alginate is water soluble, water is drawn into the fiber, of seaweeds.18 It can be seen that the ion-exchange
turning it into a fibrous gel.17 coefficients differ greatly both in terms of the different metal
The gel formation process depends on the formation of the ions against the same variety of alginate, and also for the
water soluble sodium alginate within the alginate fiber, same metal ions against alginate with different guluronic
which is again dependent on the ability of sodium ions to acid and mannuronic acid contents. For the calcium alginate,
replace calcium ions in the fiber. In a study on the binding the ion-exchange coefficients between calcium and sodium
abilities of alginate for divalent metal ions during the gel are 7.5 and 20, respectively for the alginate with high M and
formation of sodium alginate solution, Haug and Smidsrod18 high G contents.
had noted that the ability for alginate to bind divalent metal It is clear that among different metal ions, calcium ion has a
ions is related to the ion-exchange coefficient between the relatively weak binding with alginate. The choice of calcium
divalent metal ion and the sodium ion: as the divalent metal ion used for the production of alginate

½Metal ion concentration in the gel½Sodium ion concentration in the solution2



½Sodium ion concentration in the gel2 ½Metal ion concentration in solution

fibers for wound management 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
Figure 2. Structural changes during the production and saline solution. A fibrous gel is formed as a result.
application of calcium alginate fibers as a wound dressing It is important to point out that body fluid has a complex
material. composition and in addition to the ion exchange between
Copyright # 2007 John Wiley & Sons, Ltd. Polym. Adv. Technol. 2008; 19: 6–14
DOI: 10.1002/pat
8 Y. Qin

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 that wound
fluid collected from leg ulcers contained 0.6–5.9 mmol l1
glucose and 26–51 g l1 protein. James and Taylor22 showed
that a typical wound fluid contained 2.9% protein.

THE GELLING ABILITIES OF ALGINATE


FIBERS
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
Figure 3. Photomicrographs showing the swelling of high G as an aqueous solution containing 142 mmol of sodium
calcium alginate fiber when wet in normal saline, 200. chloride and 2.5 mmol of calcium chloride) for 30 min 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 560 ppm 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 when wet 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,
Figure 4. Photomicrographs showing the swelling of high M effectively turning itself into a piece of hydrogel. In clinical
calcium alginate fiber when wet in normal saline, 200. 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
sodium and calcium ions, the protein component in the gel, and in the process, the absorption of a large quantities of
wound exudate can also bind calcium ions, hence increasing exudate by the dressing.
the gel-forming abilities of the calcium alginate fibers. In a The gel swelling abilities of the alginate fibers can be
study of the composition of serous fluid formed after axillary measured quantitatively by placing 0.2 g of fiber in 100 ml of
dissection, Bonnema et al.19 found that on the first post- either distilled water, or 0.9% wt/wt aqueous sodium
operative day, the drainage fluid contained blood contents chloride solution (normal saline). After 1 hr, the fibers are
and a high concentration of creatine phosphokinase. After separated with the contacting solution and placed in a
day one, it changed to a peripheral lymph-like fluid that centrifuge tube with the bottom half filled with knitted

Table 2. The calcium release and gel swelling properties of three types of alginate fibers17
High G fiber Mid-G fiber High M fiber

Ratio of M/G About 0.4 About 1.6 About 1.8

Ca(II) content in contact solution, ppm 317.5 450 560


Gel swelling ratio in water, g/g 2.69  0.27 6.0  0.87 5.69  0.39
Gel swelling ratio in 0.9% saline, g/g 8.49  0.62 14.51  0.74 15.89  0.65

Copyright # 2007 John Wiley & Sons, Ltd. Polym. Adv. Technol. 2008; 19: 6–14
DOI: 10.1002/pat
Alginate fibers 9

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 sodium fiber. This
result suggests that one way of improving the absorption and
Figure 5. Photomicrographs of a piece of high G calcium gelling properties of the alginate wound dressing is to
alginate fiber when wet in water, 200. introduce sodium ions into the fiber.

THE GEL BLOCKING PROPERTIES OF


ALGINATE 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
Figure 6. Photomicrographs of a piece of high M calcium overall absorption of the dressing, liquid absorbed between
alginate fiber when wet in normal saline solution, 200. 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 then weighed (W) before being placed in plastic
viscose rayon fabric to contain the spin off solution. The Petri dishes (90 mm in diameter) and wetted with 40 times
centrifuge is carried out at 1200 rev/min for 15 min. After their own weight of solution A. The dish is then placed in a
that the fiber (W1) is dried at 1058C to constant weight (W2). 378C oven for 30 min. After that, the dressing is lifted out of
The gel swelling ratio is expressed as the ratio between the the solution by holding it with a forcep at one corner. The
weight of the wet sample and that of the dry sample, i.e., W1/ solution is left to drip for 30 sec and the wet dressing is
W2.24 weighed (W1). The sample is then placed in a centrifuge tube
As can be seen in Table 2, when wet in water, high G half filled with knitted gauze to contain the spin-off liquid.
calcium alginate fiber had a limited extent of swelling, with After centrifuging at 1200 rpm for 15 min, the dressing is
the gel swelling ratio of 2.69, similar to the value obtained taken out and weighed again (W2). Finally, the dressing
from cotton and viscose rayon fibers. High M alginate fibers is dried to a constant weight at 1058C for 4 hr and the weight
swell better than high G alginate fibers, however, this is weighed (W3).24

Table 3. The gel swelling properties of three types of alginate fibers containing different levels of sodium ions17
Sample High calcium fiber Mid-calcium fiber High sodium fiber

Calcium alginate content 98.3% 76.5% 54.1%


Sodium alginate content 1.7% 23.5% 45.9%
Gel swelling ratio in water, g/g 2.69  0.27 24.05  0.85 20.60  2.66
Gel swelling ratio 0.9% saline, g/g 8.49  0.62 13.42  1.03 18.58  0.94

Copyright # 2007 John Wiley & Sons, Ltd. Polym. Adv. Technol. 2008; 19: 6–14
DOI: 10.1002/pat
10 Y. Qin

Figure 7. The nonwoven structure of a piece of calcium Figure 8. Photomicrograph of a piece of alginate nonwoven
alginate wound dressing. dressing wet in normal saline, 200.

In the above mentioned experiment (W1  W)/W lateral spreading of the liquid. This so-called ‘gel blocking’
represents the standard absorption capacity of a dressing property is clinically an important feature of an alginate
defined in the British Pharmacopeia for alginate wound wound dressing. As Fig. 9 clearly shows, wound covered by
dressings. (W1  W2) represents the liquid held between the an alginate wound dressing has a clean edge, with the wound
fibers, while (W2  W3) represents that held inside the fiber. exudate absorbed into the dressings immediately on top of
When the fiber is highly hydrophobic, such as glass fibers, the wound surface.
the absorption of fluid would be held mainly between fibers
by capillary forces. On the other hand, in the case of some
ALGINATE WOUND DRESSINGS
superabsorbent fibers, most of the absorption takes place
inside the fibers. Alginate has a long history of applications in wound
Table 4 shows the absorption behavior of two types of management. It is reported that early sailors used seaweeds
alginate dressings and other non-alginate materials. Because to treat wounds, burns and eczema, and during the World
of the ion-exchange properties, alginate fibers absorb much Wars, because of shortage of cotton, dried sea moss dressings
more liquid into the fibers than other non-alginate dressings. were sent to field hospitals to treat wounded soldiers.9
It should be pointed out that in the case of a wound dressing, During World War II, Blaine25 investigated tissue reactions to
the fact that fluid can be absorbed into the fiber structure is alginate fibers and reported the use of alginate fibers for
important in several respects. First, when the fluid is hemostasis and as a bone wax substitute.26 In 1951, Blaine
absorbed into the fibers, they swell as a result. As the fiber used alginate fibers as absorbable hemostats in surgery and
expands upon swelling, the free spaces between the fibers are noted that 10 days after the implantation, the alginate became
closed, and bacteria in the textile structure or in the wound almost entirely absorbed. Blaine27 also reported that
exudates are then immobilized. This can help prevent the alginates did not lessen the antibiotic activity, could be heat
proliferation of bacteria, and reduce wound infection and sterilized, and did not promote bacterial growth.
cross infection in hospital wards. Second, if the fluid is held The first modern alginate wound dressing was brand
between the fibers by capillary forces, it can easily migrate named Sorbsan, which was launched in 1983.28 It consisted of
along the textile structure. Clinically, this would mean the a loose fibrous fleece made from calcium alginate fibers with
spreading of wound exudates from the wounded area to the a high mannuronic acid content. This was followed by other
surrounding healthy skins under the dressing, causing skin products that differed both in their chemical composition
maceration. Ideally, wound dressings should be able to and textile structures. For example, Kaltostat, a fibrous high
absorb a large amount of exudates, and contain the fluid G calcium alginate, was introduced into the market in 1986.
within the fiber structure. Later, Kaltostat was further modified to consist of a mixture
Figure 8 shows the photomicrograph of a piece of alginate of calcium and sodium alginate. The sodium alginate was
nonwoven dressing wet in normal saline. Compared to Fig. 7, introduced to improve the gel-forming ability of the fibers.
it can be seen that the fibers within the dressing are highly Alginate wound dressings are produced either as flat
swollen, blocking the capillary structure, hence limiting the sheets, which are used to cover superficial wounds, or as

Table 4. Absorption behavior of two types of commercial alginate and some non-alginate wound dressings24
Product (W1  W)/W (W1  W2)/W3 (W2  W3)/W3 (W1  W2)/(W2  W3) W3
TM
Sorbsan 11.98 73.7 15.2 4.83 0.139
KaltostatTM 16.30 47.1 14.8 3.18 0.198
Knitted fabric of viscose filament yarn 1.88 4.64 2.72 1.71 0.379
Woven cotton gauze 4.83 11.5 6.45 1.78 0.059
Polyester nonwoven fabric 18.35 67.6 3.97 17.01 0.494

Copyright # 2007 John Wiley & Sons, Ltd. Polym. Adv. Technol. 2008; 19: 6–14
DOI: 10.1002/pat
Alginate fibers 11

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 OF


ALGINATE WOUND DRESSINGS
The hemostatic properties of alginate wound
dressings
In 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
Figure 9. A leg wound covered by a piece of alginate wound within 10 days. Blair et al.30 compared the hemostatic effect of
dressing. oxidized cellulose (Surgicel), porcine collagen (Medistat),
calcium alginate (Kaltostat), and surgical gauze in liver
cavity fillers, usually in the form of ribbon or rope. The flat lacerations in the rabbit. Their results showed that calcium
dressings are normally made in a nonwoven fabric process in alginate stopped bleeding in less than 3 min compared with a
which the fibers are carded to form a web that is then mean of 5.7  0.75 min for porcine collagen, 12.5  0.9 min for
cross-lapped to form a felt. In some products, the felt is then oxidized cellulose, and >15 min with gauze.
needled or entangled by means of high-pressure water jets to Sirimanna31 investigated the use of calcium alginate fiber
give the dressing a coherent structure.1 for packing nasal cavity following surgical trimming of the
After more than two decades of development, alginate inferior turbinates. Thirty-two nostrils were packed with
wound dressings have now become one of the most versatile Kaltostat for 36–48 hr to achieve hemostasis. There was no
wound dressing materials. They have unique gel-forming bleeding while the packs were in place or after removal.
properties and high absorption capacities. It is now generally These results were compared retrospectively with two other
accepted that the wound heals better in a moist condition, treatments, i.e. trousered paraffin gauze and glove finger
and the ability to form a moist gel has given the alginate packs, both of which had been associated with bleeding in
dressings their unique characteristics. They are gaining over 50% of cases either while in situ or after removal. In a
widespread use in the management of exuding wounds such second study, the three types of packings were compared
as pressure sores and leg ulcers. prospectively.32 All three were similarly effective in
Table 5 outlines the key structural features for several preventing bleeding while in situ, but the alginate caused
types of commercial alginate wound dressings. It is significantly less bleeding on removal.
important to point out that for an alginate wound dressing, The hemostatic effect of the alginate fibers was attributed
there are three structural levels to differentiate different to the calcium ions released from the fibers, which can
products, i.e. molecular, fibrous, and textile structures. activate platelet coagulation. In this respect, products made
Alginate is a copolymer and its molecules differ on the from high M alginates are more effective than their high G
relative proportions of a-L-guluronic acid and b-D-mannuronic equivalent. Evidence for the hemostatic activity of one high
acid monomers. During the wet spinning process, sodium M alginate dressing, Sorbsan, was produced in a study in
alginate is converted into calcium alginate. In some cases, which the dressing was applied to experimental, full, and
part of the alginic acid in the fiber can form salt with sodium partial thickness wound models for up to 14 days to assess its
ions, resulting in a mixture of calcium/sodium alginate. effects on healing. Histological evaluation showed the
Different fibers can differ in the metal ion composition as dressing to be an effective hemostat, generally well tolerated
well as the various types of additives that are blended into by body tissues.33
the fiber during the production process, for example, CMC is In a detailed study on the hemostatic properties of various
added into the fiber to increase the absorption capacity. alginate wound dressings, it was shown that high M type
During the production process for wound dressings, the dressings generally have better hemostatic properties than

Table 5. Key structural features of seven commercially available alginate wound dressings29
Ratio between guluronate Ratio between calcium Nonwoven
and mannuronate contents and sodium content structure

SorbsanTM 39/61 96.6/3.4 Unneedled


TegagelTM 39/61 96.6/3.4 Hydro-entangled
AlgosterilTM 68/32 99.6/0.4 Needled
KaltostatTM 68/32 80/20 Needled
Tegagen HGTM 38/62 65/35 Needled
CurasorbTM 68/32 99.2/0.8 Needled
UrgosorbTM
Alginate/CMC ratio  85/15 68/32 95.2/4.8 Needled

Copyright # 2007 John Wiley & Sons, Ltd. Polym. Adv. Technol. 2008; 19: 6–14
DOI: 10.1002/pat
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 alginate


wound dressings Figure 11. The antimicrobial action of silver containing algi-
For alginate fibers, it is well known that when they are in nate fibers against E. Coli.
contact with wound exudate, the calcium ions in the fibers
exchange with sodium ions in the fluid, and the fibers are and there was increased rate of bacteria growth in some
transformed from water insoluble calcium alginate into cases.
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 The wound healing properties of alginate
water and swell, the spaces between the fibers are closed and wound dressings
any bacteria that are carried in the wound exudate are On contact with wound, alginate wound dressings can
trapped in the wound dressing. This can help reduce the stimulate macrophage activities. The interaction between the
spreading of bacteria, giving the alginate wound dressings alginate molecule and macrophage cells plays a key role in
bacteria static properties.35 many physiological and pathophysiological processes
The development of silver containing alginate fibers has during the wound healing process by synthesizing various
enhanced the antimicrobial activities of alginate wound biologically active molecules called cytokines. Tumor
dressings by the sustained release of the broad spectrum necrosis factor-a (TNF-a) is an important cytokine, having
antimicrobial silver ions.36 Figure 10 shows the antimicrobial cytotoxic properties against both tumor cells and normal
mechanism for the silver containing alginate wound cells infected with intracellular pathogens. It is also a very
dressings. As the dressing absorbs exudates, the fibers important inflammatory mediator, which modulates many
absorb liquid into the fiber structure and swell as a result, physiological and immunological functions and has been
reducing the interfiber spaces and effectively trap bacteria in implicated in inflammatory conditions. Otterlei et al.37
the nonwoven structure. The release of silver ions from the compared the ability of different alginates to stimulate
fibers then kills the bacteria that are trapped in the alginate macrophage cells to produce TNF-a, interleukin-1, and
wound dressing, thus making the dressings highly anti- interleukin-6. They reported that high M alginates were
microbial. approximately 10 times more potent in inducing cytokine
Figure 11 shows the antimicrobial action of silver production than high G alginates and therefore proposed
containing alginate fibers against Escherichia Coli. There that mannuronic acid residues are the active cytoki-
was 100% reduction in bacteria count within 5 hr after the ne-inducers in alginates. Other authors have also produced
fibers were placed in contact with solutions containing the evidence to suggest that it is MM blocks rather than GG that
bacteria. Interestingly, although the Sorbsan alginate fibers is responsible for cytokine stimulation and antitumor
showed some antimicrobial activity, in the solution contain- activity. A treatment of high M alginate with C-5 epimerase,
ing the other alginate fiber and AquacelTM (made of which converts b-D-mannuronic acid into a-L-guluronic acid,
carboxymethyl cellulose), antimicrobial effect was not noted 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 dressings


The 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 Army Medical 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.
Figure 10. The antimicrobial mechanism of the silver con- During a subsequent assessment of the use of alginate as
taining alginate wound dressings. hemostats and wound dressings, Blaine25 reported the
Copyright # 2007 John Wiley & Sons, Ltd. Polym. Adv. Technol. 2008; 19: 6–14
DOI: 10.1002/pat
Alginate fibers 13

apparent lack of toxicity following a series of animal studies acceptability of the dressing. A total of 155 donor sites were
in which fibers were implanted into animal tissues, and gels examined, among these, 130 were treated with alginate and
made from alginates were used to treat experimentally 25 with paraffin gauze. Sites treated with the alginate healed
produced burns. Successful use of alginate-derived materials in 7.0  0.71 days, whilst the paraffin gauze dressed wounds
in aural surgery and neurosurgery was reported by Passe took an average time of 10.75  1.6 days to heal. Patient
and Blaine40 and Oliver and Blaine,26 respectively. Bray comfort and the quality of healing with the alginate were
et al.41 described the results of a 3-month trial on the use of significantly better than that achieved with gauze.
alginate in the casualty department of Croydon Hospital.
Alginates in the form of films, wool, gauzes, and clots formed Pressure ulcers
in situ by mixing sterile solutions of calcium chloride and Sayag et al.12 compared the efficacy of an alginate (Algosteril)
sodium alginate, were applied to a wide range of wounds, with that of dextranomer paste, an established local
including burns, lacerations, ulcers, and amputations. In all treatment, in a prospective, randomized, controlled trial of
cases, healing was rapid and uneventful. By the late 1940s 92 patients with full-thickness pressure ulcers. A minimum
and early 1950s, alginates were being used in some 70 40% reduction in wound area was obtained in 74% of patients
hospitals in the UK over a range of surgical specialties.27 in the alginate group and 42% in the dextranomer group. The
More recently, the first clinical report regarding a fibrous median time to achieve this reduction was 4 weeks for the
alginate wound dressing was published in 1983 when Fraser alginate and more than 8 weeks for the dextranomer. Mean
and Gilchrist8 and Gilchrist and Martin42 described their surface area reduction per week was 2.39  3.54 cm2 and
experiences with the Sorbsan alginate dressing in the 0.27  3.21 cm2 in the alginate and dextranomer groups,
management of foot disorders and a variety of skin lesions, respectively. The authors concluded that the striking efficacy
following a clinical evaluation in a group of hospitals in the of the alginate dressings suggested that they may have
Sunderland area. The results of these studies were very pharmacological properties to wound healing.
positive and supported the findings of Blaine some 40 years
earlier. Further papers described the use of Sorbsan in the
NOVEL USES OF THE GEL-FORMING
management of problem wounds including infected trau-
ABILITIES OF ALGINATE FIBERS
matic wounds and leg ulcers.43,44
Alginate wound dressings are used on many types of In addition to nonwoven wound dressings, alginate fibers
wounds with medium to high levels of exudates. Some of can be used to make a number of novel composite materials
these wounds are described below. for wound management and other biomedical applications.
Qin and Gilding made fiber reinforced alginate gel by
Leg ulcers dispersing chopped calcium alginate fibers in a solution of
Thomas and Tucker carried out a controlled trial of an sodium alginate. During drying, the calcium ions released
alginate dressing involving 64 community patients with leg from the alginate fibers crosslinked the sodium alginate, and
ulcers.45 The patients were allocated to treatment with either a fiber reinforced sheet of alginate was formed. When in
an alginate dressing (Sorbsan) or paraffin gauze (tulle) as a contact with water, the sodium alginate component in the gel
control. Only 4% of the ulcers treated with tulle healed absorbs water into the sheet and a hydrogel is formed. If the
during the study, while 31% of those treated with the alginate mixture of calcium alginate fiber and sodium alginate
healed completely. The average healing rate achieved with solution is placed in a freezer to form a sheet of solid ice,
the alginate was over four times of that with tulle. Overall, and then taken immediately to a freeze drying machine, a
73% of alginate patients showed improvement during the freeze-dried pad can be prepared over a period of about
trial, compared with 43% in the control group. 20 hr. The resultant product is a porous dehydrated hydrogel
capable of absorbing more than 20 g of normal saline for a
Burns and donor sites gram of the sheet material.46
Alginate wound dressings are ideal for the treatment of In order to donate moisture to dry wounds, the calcium
burns and donor sites, where their hemostatic and absorbent alginate fibers can be mixed with sodium alginate solution to
properties are most useful. Groves and Lawrence10 com- form amorphous hydrogels.47,48 By mixing 1 kg of calcium
pared Sorbsan with a standard gauze pad. In a laboratory test alginate fibers with a length of about 10 mm, 1.2 kg of sodium
the alginate absorbed nearly three times as much citrated alginate and 50 g of sodium citrate in 40 l of water and 8.5 kg
blood as the gauze; when applied to fresh, split-thickness of propylene glycol, a viscous fibrous gel can be formed, with
donor sites for 5 min after excision, blood loss from the sites a viscosity of about 800,000 mPa s. This type of gel can be
treated with the alginate was almost half than from those applied on dry wounds to donate water to the devitalized
treated with gauze. tissue, allowing them to separate from the wound, so that a
The effect of long-term application of alginates to donor clean wound surface can be developed.
sites was investigated by Attwood.11 In an initial study, 15 It is also possible to produce sheet hydrogel by impre-
patients with split skin grafts had half of their wound ganating a nonwoven alginate felt with a sodium alginate
dressed with an alginate (Kaltostat), and the other with solution.49 For example, a nonwoven calcium alginate felt
paraffin gauze. Every area dressed with the alginate showed with a weight/unit area of about 60 g m2 was treated with a
significantly better healing than the corresponding ‘control’ 2% sodium alginate solution dissolved in a 80/20 mixture of
area. The second phase of the study assessed the time to water and propylene glycol, with the ratio between solution
complete healing of alginate-dressed areas and patient to felt at 40 to 1. The fibers in the nonwoven felt interacted
Copyright # 2007 John Wiley & Sons, Ltd. Polym. Adv. Technol. 2008; 19: 6–14
DOI: 10.1002/pat
14 Y. Qin

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Surg. 1999; 165(1): 9–13.
hydrated sheet hydrogel for the treatment of superficial 20. Frohm M, Gunne H, Bergman AC, Agerberth B, Bergman T,
wounds with low to medium level of exudate. Boman A, Liden S, Jornvall H, Boman HG. Biochemical and
Renn et al.50 developed a method of producing an antibacterial analysis of human wound and blister fluid. Eur.
J. Biochem. 1996; 237(1): 86–92.
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sodium alginate solution. They dispersed surfactants in the wound exudate. Wound Rep. Reg. 1996; 4: 234–239.
sodium alginate solution to create a foamy mixture. When 22. James T, Taylor R. Wound exudate In ‘Proceedings of a joint
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Copyright # 2007 John Wiley & Sons, Ltd. Polym. Adv. Technol. 2008; 19: 6–14
DOI: 10.1002/pat