Indian Journal or Fibre & Tex tile Research Vol. 27. December 2002, pp. 434-450

Review Article

Use of polysaccharide fibres for modern wound dressings

S Ghosh & M Jassal"

Department of Tex tile Technology, Ind ian Institute of Technology, New Del hi 11 00 16, India

Received 31 i ll iv 200 1 .. revised received alld accepted 9 October 200 1

Polysacchari de fib res like al ginate, chitin, chi tosan, mod ified ce llulos ic fibres , dex tran, hyaluronate. pectin and ( 1 -3)~-D-glucan s are being used for modern wou nd dress ing. Th is paper prese nts an ove rview of wound heal ing mechani sm and preparation and application or above biopo lymeri c fi bres in the hi ghl y specialized biomed ical fie ld or wound management.

Keywords: Alginate, Chit in . Dex tran, Hya luronate, Polysacc hari de, Wound dressi ng

1 Introduction Med ical tex til e has emerged as a new branch with

high potential in the area of textile technology due to the recent advancements and innovati ons in both medical procedures and tcx til e engineering. Some tex tile products have been in regular use in medi cal and surgical areas and wound dress ings have been an essenti al part of them. The fun cti ons of wound dress ings are to give protection against in fec ti on, to absorb blood, promote hea ling and , in some cases, apply medi cati on to the wound , combat odour, re li eve pa in and promote autolyt ic debri dement. As more and more in fo rmati on is being ava il able about wound heal i ng mechani sm, vari ous new types of sophist icated wound dress ings are being deve loped to provide best possible treatment at optimum cost. Now wound dress ings can be made from a wide vari ety of materi als including salts of alginic acid, starch and carboxy methyl cellulose, chitin I , chitosan , polyurethane, poly-L- Leucine, silk2

, wool3, etc either alone or in combination to fo rm hydrogel, bead, film and fibrous structure like woven and nonwoven.

The shortcomings and drawbacks of traditional wound management have led to the development of new materi als which can improve wound healing process in a faster and better way. Polysaccharides are one or the most widely di stributed macromolecular organi c compounds in nature, present both in pl ants and animals. Polysaccharides are polymeric substances composed of monosacchari des as

"To whom all the correspondence shoul d be add ressed. Phone: 659 1426; Fax: 0091-01 1-6858 11 2; E-mai l: manjcetjassa l@hollllail.co m

repeating units and joined by glycosidic lin kages . Most widely known polysaccharide is ce llul ose whi ch occurs in hi gher pl ants and in some algae. Lesser known polysaccharides include chitin and chitosan whi ch are present in yeas ts, fungi and shell s of orthopods. These are ca lled 'fibrous polysaccharides'. Hemi cellulose and pectins, found in hi gher plants, have gel forming capac ity and are called ' matrix polysaccharides'. Polysaccharides can se rve a va ri ety of fun cti ons. One of the most potenti al and tremendously advancing areas of their applica ti on is in wound dress ing.

The fri endl y effec t of pure biopoly mers of carbohydrate family towards wound heali ng is well known fro m long time. Traditi onally, a wide va ri ety of materials have been tri ed to cover wounds and to reduce bl eeding, such as leaves, grass. animal fat, honey, cob web and spider web. There have also been some instances of using marine algae and crab shell s. Long ago, it was fo und that a partic ul ar type of sea weeds, which actually contain alginate, had been used by the sa ilors to cover their wounds. In some cultures of world, crab shell s and fun gi, whi ch conta in chitin , were used fo r accelerating wound healing,. In th is paper, an attempt has been made to present an overview of various types of polysaccharide fibres used in modern wound dressings (Table 1) and the methods used to prepare these fibres. Polysacc hari de fibres can be engineered up to the mo lecu lar level to achieve the desired properti es like highcr absorbency and ge lling properties. They can then be blended with other fibres or used singly and converted into a variety of tex tile products in woven, knitted and

GHOSH & JASSAL: USE OF POLYSACCHARIDE FIBRES FOR MODERN WOUND DRESSINGS 435

nonwoven form s for application as wound • Necrotic wounds : black in colour, covered with hard dev itali zed epidermis . dressing(Table 2).

2 Mechanism of Wound Healing • Sloughy wounds: yellowish in colour, conta in a

layer of adherent creamy slough. Production of an effective wound dress ing needs a

clear understanding of the process of ti ssue repair. Wounds may be classified generally in following four types:

• Granulating wounds: red in colour, contain hi ghly vascularized granulating tissue.

• Epithelialising woullds: pink margin surrounding the wound, indicating epitheli ali sation has started around the wound margin. Tab le I- Polysaccharides used for wou nd dressing

Polysaccha rides Wound healing involves a variety of complex biological mechani sms. Wound repair may be categorized into three steps: (i) inflammation, (ii ) ti ssue formati on,and (iii) ti ssue remodeling. These three phases are not mutually exclusive but rather overlapping in time. The total healing process can be divided into following three stages4

.5

:

Ac idi c Basic

Alginate

Hyaluroni c acid

Ch itin

Chitosan

Polysaccharide

Calcium alginate

Chitin

Carboxymethyl cellulose

Carboxymethyl cellulose + Pectin

Dextran

Pec tin

Glucan

Neutral Sulphated

Cellulose Heparin

Dextran Heparin sulphate

(1-3 )- Dermatan sulphate glucan

Keratan sulphate (i) Latent period: Up to 5-7 days, there is no gai n In Chondroitin sulphate

Table 2 - Some polysaccharide products used for dermal app li cati on

Trade name

Kaltostat

Kaltostat

Sorbsan

Sorbsan

Ultraplast

Fibracol

3M Tegagen H G

3 M Tegagen H I

Seasorb

Beschitin W

Aquagel

Hydrofibres

Biorilm

Dermill ex

Comi"eel ulcer

Maxorb

Granullex

Restore

Debri san

DuoDerm

Glucan

Company

CalgonlVestal

Cair

Steri seal

Surgical Medica l

Characteristics

Gel(for sk in cove ring)

Carded & needl e tucked web

Nonwoven pad (for skin cove ring)

Carded web

Knitted

Joh nson & Johnson Contains coll agen

3 M Limited Hi gh gell ing

3 M Limited Hi gh integrity

Coloplast Fibre free dress ing, allows one piece removal

Mori hila

Convatec

Biotrol Film, contains Karaya gu m

John son & Johnson Film, contains Karaya gum

Colopl ast Film, contains elastomer, outer protecti ve layer of polyurethane

Medline Nonwoven, contains alginate

Bristol-M yers Squibb

Holli ster

Phannacia

Convatec

Brennen Med ica l

Sheet. contains elastomer, outer layer of pol yure­thane film

Sheet, contains ge latin and elastomers

Small beads, powder or paste

Sheet, contains gelatin and elastomers

Mesh-reinforced dressing

436 INDIAN J. FIBRE TEXT. RES. , DECEMBER 2002

strength. Neutrophils clean the wound area and re­move the foreign particles like bacteria through re­lease of enzymes and toxic oxygen products. Platelets and rnacrophases release substances which st imulate the multiplication of fibroblastO, resulting in fibroblas t prol iferation.

(ii ) Period of fibroplasia: During next 5 days or so, there is a rapid increase in strength due to increase in collagen content7 secreted by fibroblasts. (ii) Maturat ion period: Can last for many weeks. The collagen content reaches a plateau.

Several times, injury results in disruption of blood vessel releasing blood constituents. Blood coagulation and platelet aggregation generate fibrin-rich clot that blocks severed vessels and fills any di scontinuity in the wounded ti ssue. The clot within wound space provides a provisional matrix for ce ll migration . When sk in is punctured, the damage often destroys the weave like structure of collagen that gives skin its strength. But instead of rebuilding the complex coll agen weave as before, the body creates a quick fix by produc ing thin strips of collagen. The newly formed 'scar tissue' , a connective tissue poor in elast ic fibres, separates the wound edges. The dead tissue rapidly shrinks by losi ng moisture and progressively becomes black and hard . This process of dehydration may resu lt in pain , because of the contraction force of shri n kage of dead tissue the nerve endi ngs in that area stimulate receptors around the wou nd margin.

The epitheli al cells from the wound margin move quickly to di ssectx.lJ clot and damaged stroma. If the basement membrane is destroyed by injury , then the epidermal cells migrate over a provisional matrix formed by fibrin, fibronectin 9

, tenasin iO, vitronect in l l

and stroma l type I collagen 12. As the re-epithel ial iza­tion is going on, basement membrane protein reappears in an ordered sequence from the margi n of the wound inward in a zipper-like fashion 9

. Epidermal cells again firmly attach to the basement membrane and to the underlying neodennis 13

·14

• Subsequently, angiogenesis 15 (process of new blood vessel formation) takes place. By this time, wounds gain 20-30% of their final strength. After this period, the rate at which wounds gain tensile strength is slow.

It has been demonstrated that a ' moist wound environment ' encourages healing more as compared

d d·· 16 17 Th f' to a ry con Itl on '. e presence 0 mOi sture on the wound surface helps in migration of healthy skin cells, production of granul ation tissue and the process

t' . h I' I' . IR 19 d I . o eplt e la Izatlon ' an a so prevents scarnng. Fresh wounds initially produce a large amount of

fluid exudates, which provides a ferti ie environment for bacterial growth and infection. Therefore, efficient absorption of fluid exudates is needed wh il e maintaining a sterile environment at the wound site20

.

To keep the optimum level of moisture, 'intelligent dress ing' has now been prepared by Carrington Laboratories of Irving, Texas, USA21 which donates moisture to the dry wounds and absorbs moi sture from wound that contains too much exudates. Gas exchange through the wound dress ing is also needed, because the presence of high CO2 concentration increases the acidity and slows down the healing process, and a low oxygen concentration decreases the regeneration of tissue cell or may help the proliferation of anaerobic bacteria.

3 Requirements of Modern Wound Dressing The primary aim in wound management fi eld is to

obtain a thin elastic transparent film or layer with a high water vapour permeability which does not allow water leakage, microbial penetration or tissue ingrowth , has no cytotoxicity and has suffi cient breaking strength to be peeled from intact sk in without breaking, but which does not stick to the wound bed. Therefore, there are two opposite requirements for the wound dressing to meet: (i) it should prevent dehydration of the wound and obstruct bacterial entry, and (ii) it should be permeab le enough to allow the passage of discharge through pores.

Wound dressing should be designed to produce optimum condition for healing. The type of dressing used will involve the type of skin wound, its depth, its cause and the stage of wound healing. The general requirements of a modern wound dressing can be summarised as fo ll ows:

The dressing must be ab le to remove excess ex u­dates and toxic component. It shou ld maintain a hi gh humidity at the wound

d d . . t' ?? an ress lng Inter ace--. It should all ow gaseous exchange. It should provide thermal insulation and prevent heat loss. It must protect the wound against attack of micro­organisms. It shou ld be free from particulate matters and toxic wound contami nants . It shou ld be removable without causing pain and trauma at the time of change of dressing. It should be able to reduce or eliminate foul odours that may be a source of distress to pa­tient 's family and carers.

GHOSH & JASSAL: USE OF POLYSACCHARIDE FIBRES FOR MODERN WOUND DRESSINGS 437

It should not disturb new ti ssue growth. It should preferably be versatile so that it can be used on many types of wounds. It must protect against mechanical damages from an external cause. .It should be cost effective.

Traditional dressings, such as cotton gauzes and surgical sponges, have not been conducive for healing extremely deep wounds or wounds with irregular shapes. They have been unable to absorb large amounts of ex udates and tend to adhere to the wound upon removal. Those traditional dressings are generally made up of cellulosic fibres, such as cotton and viscose rayon fibres, in the form of woven or nonwoven gauzes. The fibre structure is physically, chemically or biomedically more or less inert to the wound healing environment and sometimes the fibre tends to stick to dry scar during the course of treatment. The new sk in may grow into the pores of knitted/woven structures.lt can also destroy the regenerating tissues. This can delay the healing process, cause scarring,and can reopen the wound for entrance of bacteria. As it sticks to the scar, its removal becomes painful or traumatic and can again stal1 bleeding from the wound site. Therefore, though highly absorbent, traditional dressings are problematic.

A tightly woven wound dressing gives a smoother dress ing pad and probably absorbs more quickly, but a loose structure provides more bulk for oreater

. ?3 . b

protection of wound- . Wound dress ll1gs are generally made of three layers2'!: (i) wound contact layer, (ii) absorbent layer, and (iii) base materi al. The wound contact layer should prevent adherence of the dressi ng to the wound for easy, pain-free remova l and speedy comfortabl e dressing changes. The absorbent layer is held between the wound contact layer and the flexibl e base material. The absorbent pad absorbs blood or fluids and provides a cushioning effect to protect the wound . The absorbent pad can be made from conventional fabric, foam , fibrous structures of polyester, and cellulosic materials such as cotton, rayon , wool, superabsorbents, etc.These can be c1assified2°as follows: • Hydrocolloids: Colloids in which hydrophilic

granules are uniformly dispersed in the elastic ad­hesive matri x. The granules are usually made of hydrophili c polymers such as sodium carboxy­methyl cellulose, pectin , gelatin and sodium algi­nate. When the dressing is applied to fresh wound, the hydrophilic granul es absorb the ex u­dates fluid and form a hydrogel.

• Sheet hydrogels : Hydrophilic polymers are par­ti ally crosslinked to form a three- dimensional network . When applied to wounds such as dermabrasion , minor burns and skin donor sites, these dressings can relieve pain also.

• Amorphous hydrogels : Thick viscous fluids, generally made from modified corn starch, can be used due to their excellent absorbing property and ability to maintain a moist environment. In dry and sloughy wounds, moisture environment helps in wound debridement. Amorphous hydrogels are useful in treating cavity wounds because the fluid property has good effect in the packing of deep wounds.

• Alginate gel : Alginates are very much useful in the treatment of a wide range of wounds due to superi or absorbency and gel fo rmation property.

The base material may be coated with acryli c adhesive to hold the dressing in place. Thi s polymeri c support layer can be made from a non-adhering wound dressing material , preferably a polyolefin such as polyethylene or polypropylene.

The Food and Drug Administration (FDA), USA, has classified wound dressings into following four types which came into effect from 4th November 1999: • Non-resorbable gauze/spollge dressing : It is for

external use, placed upon patient's wound to ab­sorb ex udates. It may be strip, piece or pad made from the nonwoven mesh, woven structure made from cotton or other derivatives of cellulose.

• Hydrophillic wound dressillg : It consists of non­resorbable materials of hydrophilic properties which can absorb exudates such as cotton, algi­nate, dextran , derivatives of cotton and rayon.

• Occlusive wound dressing : Non-resorbable de­vice to cover the wound provides a moist wound environment, and allows exchange of gases . It consists of synthetic polymeric material s such as polyurethane, with or without adhesive backing.

• Hydrogel dressing: This dressing is intended to cover a wound, to absorb wound exudates, and to protect against abrasion , friction and desiccation contamination. It is made of a non-resorbable ma­trix made of hydrophilic polymers or other mate­rial s in combination with water (at least 50%).

There may be another typc of wound dressing, viz. interactive wound dressing. This dressing contains added drugs, anti microbial agents, growth factors or material s deri ved from animal sourcc.

438 INDIAN J. FIBRE TEXT. RES. , DECEMBER 2002

4 Alginate Wound Dressing Alginate is a natural polysaccharide present in

many species of brown sea weeds of the type laminariae. Alginate can be found from the species of marine algae like Ascophyllum nodoslll1 , Durovillea pro/a/om/III, Lasonia nigrescens and Ecklonia l1Iaxirna. Alginic acid IS a linear 1,4- linked copolymer of f3-D- mannuronic acid (M-unit) and its C-S epimer a-L-guluronic acid (G-unit) (Fig. I). The G and M units are joined together in homopolymeric and heteropolymeric sequentially alternating blocks. The proportion of the various blocks depends on the sea weed source of origin , the season of harvest, and part of the algae from which the alginate is extracted25

. Alginic acid and its water-soluble sodi um salt have been manufactured for decades due to their great ability to form highly viscous solutions even at moderate concentration. This property has been used in food processing, textile pnntlllg thickener, pharmacology- as a drug carrier26

, entrapment of biocatalyst in polymeric matrices27.28 , for cell

2R- ) ? d • d· . I entrapment . -, an as a support lor ImenSlona culture of specific cells such as chondocytes33

. In case of calcium alginate gel beads prepared by the conventional immobil ization method, cells on the surface and near the surface can easily leak from the beads and can grow rapidly in the medium rather than in beads31

.

4.1 Structure

The M block section is flat, while the G block section is buckled34

. This sectional nature of the alginate polymer confers different backbone chain flexibility to the polymers in solution. The differences in flexibility are not due to the differences in H bonding, which is present to the same extent in each monomer. But these differences in fl ex ibility generate from a greater restriction about the carbon-oxygen bonds joining the monomer. The a (l-4) linkage of the guluronic acid residue introduces greater steric hindrance from the carboxyl groups. For this reason, high M content alginate chains are more flexible in solution than high G content alginate chains35

. 36. It has been reported that guluronic acid binds calcium ions more firmly then the mannuronic acid. The ability of gel formation of alginate is greatly increased by the presence of divalent ions such as Ca2+ which can be complexed by carboxylate groups of alginate in a tetradentate structure which can be explained in terms of well - known egg-box model3? (Fig. 2). The egg-box model was proposed to explain poly-L-

H H H H H

1100- OH I \-ooc H H I \ coo-

' 0 I H H" t-rO;<\.-OliO H~H /t-O~f '~H Oft :to HG ·~ f..\~ o 0 70H

H d r \OH H H T ... -ooe OH H / a H /" ::-\.- 0 ---t--H y H H --'" - 0-_

OH \ coo- OH T H H H

(c )

Fig.1 -Structurc or alginatc backbonel (a) poly(guluron ic acid) scquence; (b) poly(mannuronic acid) scqucncc ; <lnd(c) copolymcr scquence]

/~

~J/ ° o~o O'\.. ~OO O~\ ~II '-'-. .,-_ ___ ____ ---'>\7 _. ___ . _ _ _ _ _ --,

Fig. 2- Egg-box modcl

guluronate sequences of alginate in which the junction zone is an alignment of helices with two anhydrogalacturonic acid units per turn. The helices are held together by chelate-bound Ci+ions. As shown in Fig. 2, some of the carboxylate groups are engaged in chelate binding of calcium if the egg-box is dimerisation of the molecules and the rest of Ca2+ ions are ordinarily bound. Equi librium dialysis experiments can be displaced by subjecting the salts to a large surplus of monovalent ions3x

. The dimeric junction zone strongly binds the Ca2

.,. ions, which are inside the egg-box, whereas the Ca2+ ions outside the

GHOS H & JASSA L: USE OF POLYSACCHARIDE FIBRES FOR MODERN WOUND DRESSINGS 439

egg box are less strongly bound. Alginate rich in guluronic acid forms stronger gels than alginate rich in mannuronic ac id. So, hi gh G alginate fibres onl y swell sli ghtly in presence of saline solutions, whereas high M fibres swell enormously.

4.2 Preparation One of the earliest attempts3~ of preparing al ginate

gel was by int roduction of cal cium ion into sodium alginate solution. High-strength gels were prepared from alginate containing hi gh proportion of G blocks. Alginate can be made into fibres by wet spinning, i.e. by extruding the sodium alginate solution through fin e holes into a calcium chl oride bath . The bas ic principle of wet spinning is that polymer dope from the spinneret jet passes through coagul ation bath containing a mi xture of so lvent and non-solvent. In the coagul ation bath , two-way mass transfer takes place, i.e. solvent from the polymer gel di ffu sing out in the coagul ati on bath and the non-solvent from the bath diffusing in . Thus, the polymer is precipitated from the solution and a solid 'gel fil ament ' fo rms. Some algi nates (Na-alginate, K-al ginate) are so luble in water and other algi nates (Ca-alginate, Zn-alginate) are in soluble in water as in alginic ac id .Water­insolu ble alginate fibres have been made by ex trusion of an aqueous so lution containing a precipitating (insol ubili sing) cati ons, e.g. ca lcium. As the sodium algin ate exchanges ion with calcium ions in the bath, I I · I ' f' l . . , I ~() ~ I t le ca clum a glllate I ament I S preclpltatec out ..

Thi s fil ament upon stretching, washing and drying provides the fibres that can be made in to wound dress ing by either woven or nonwoven process. The interaction between the alginate fibres and ex uding liquid creates the calcium-sod ium alginate gel, whi ch is hydrophilic, permeable to oxygen, impermeable to bacteria and helps the fo rmat ion of new t i ss ue~2. The nonwoven alginate web can be made from airblown or crosslapped corded web. This nonwoven web is then fed into a conventi onal needle-punching mach ine, whi ch interlocks the fibres and enhances the overall integrity and strength retenti on property of the algin ate web.

During the sp inning process, some med icaments can be incorporated into fi bre core, whi ch can be included in water-solu ble alginate dope before ex trus i o n (s pinning)~3 . Medicaments can also be attached by physical means to the surface of fibres after spinning by hydrogen bonding, absorpti on or van der Waals' in teraction and chemi cal cross linking interaction, such as ioni c interacti on (sa lt fo rmati on).

4.3 Application Applicati on of alginate in medical purposes had

been reported quite earli e r4~A5. The fibrous alginate dress ing may be woven, nonwoven or knitted fab ri c. The alginate dressings require moisture to fun ction correctl y and , therefore, they are not suitable fo r dry sloughy wounds or fo r wounds covered with hard necrotic ti ssue. Alginate dress ings maintain a physiologicall y moist microenvironment wh ich promotes healing and the fo rmation of granul ati on ti ss ue. Alginate dress ings are very useful for moderate to heavily ex uding wounds23. For shallow and heav ily ex uding wounds, such as leg ulcers, fibrous sheet dress ing made from alginate fibre can be used. For epitheli ali zing wounds, alginate dress ings are advantageous over cellulose dress ings due to the reason that they can be removed without causing pain . On contact with wound ex udates, alginate fibres have the unique ion-exchange properties that can make them an ideal materi al fo r advanced wound dressings46. As the sod ium ions come from ex uding wound, the calc ium-sodium ion-exchange process starts. The alginate fibre loses calcium ions to the wound and at the same time part of the fibre becomes sodi um alginate. Since sodiu m alginate is water so luble, the fibre swell s to fo rm a gel, whi ch on completi on of the treatment can be eas il y removed with a rin se of warm sa line wate r~7 . Commonl y used surgica l dress ings cont ain eq ui va lent rati o of ca lciu m to sodium in the range of 30:70 to 70:30 or even 95:5 . Before appli cati on to wound, the common practi ce is to wet the dry dress ing with water or saline so lu tion. But the gels used in wound dress ing have hi gh moisture content and do not req ui re wetting before app li cat ion. Alginate materi al used in dress ing may also incorporate cati ons such as zinc, magnes ium and cobalt for therapeutic purposes.

Alginate dress ings have been used in foo tcare (l ike sinus drainage), fissures, hyper-granulati on tissue, interdigi tal macerati on, heloma moll e and other les ions. It can be used in treatment of diabeti c and

I · f' I ~8 ~9 D' b ' d I ' I trop llC oot u cers '. Ja etl c an trop l lC u cers are normall y slow healing and become chro ni c and are characteri zed by oedema, infl ammation and bacteri al co loni zati on. Applicati on of alginate dress ing leads to ready removal of bacteri al in fec ted ex udates and earl y development of healthy granul at ion ti ssue49. In an ill vitro study to examine the effect of ca lcium algin ate on the prol i fe rati on and mobil ity, uti I izing human dermal fibroblast, mi crovascul ar endo thelia l ce ll (HM EC) and keratinocyte cu ltu re, it has been found

440 INDIAN 1. FIBRE TEXT. RES., DECEMBER 2002

that calcium algi nate increased the proliferation of HMEC and keratinocytes through calcium ions50

.

Sil ver containing agents can be added to alginate fibres from an aqueous dispersion or by wet spinning method51

. This type of alginate fibres can be used as a carrier for wound healing products52

.

A method of preparation of dressing is presented in US patent 5 470 576, in which woven or nonwoven absorbent pad made from cellulosic fibres like cotton are impregnated with calcium and sodium alginate. The ratio of calcium and sodium alginate is around 68:32 by weight. Then mechanical softening is done by mi crex ing or microcreping process53

. Institute of Chemical Fibres, Lodz, Poland, patented S~ fi lament and staple alginate fibres of 2.5 dtex having strength of 17-22 cNltex and elongation of 12- 16%.

A number of compan ies made and patented thei r alginate dressings, viz. Johnson & Johnson Medical, Arlington, Texas, USA 55; De Royal Industries, Powell, Tennessees6 (US patent 5 674 524); and Innovative Technologies of Winsford, UKs7 (US Patent 96 10106). The De Royal Industry 's dressing consists of a fibrous alginate layer which is need le­punched upon a non-alginate back ing. The fibres from alg inate layer penetrate into and are interlocked with the backing web. The backing can be made from either acrylic/cotton or polyurethane foam, or by woven/k nitted fabrics made from alginate fibres.

Bristol-Myers Squibb, Princeton, New Jersey, USA (US Patent 5 986 164) claimsR that their dressing is more soluble than ex isting products and can more eas il y be removed from wounds by washing, because the fibres hydrate quickly and the amount of lateral fluid transportation by capillary is reduced. This will reduce the amount of ex udates transported to ti ssue sUITounding the wound and the change of maceration of that ti ssue will be reduced. This company also produced an alginate fibre with sustained release property. Medicaments are incorporated into the fibre 's core and also attached to the fibre surface for more rapid releases9 (US Patent 5 690 955). Di ffe rential release may be required for a particular wound , as initi al rapid release of m~dicaments,

followed by slower and controll ed release. This also leads to the opportunity of use of different medicaments to the wound in different times of treatment. Time taken for all the medicine to be released will depend upon the amount of medicine used, spinning conditions, fibre properties and wound conditions. The company suggests to use med icaments like antibacteri al agents (like

chlortetracycline), anti protozoal agent (like promethazine), antifungal agent, nucleos ides, hormones (like noradrenalin), ant i- inflammatory agents (like predn isolene).

Sorbsan ™ (Surgical Medical, Redd itch, Worcestershire, England) is a carded web of alginate

TM fibre . Kaltostat (Cair Ltd, Adershot, Halt, England) is a carded and needle-tucked web of alginate fibres. Ultraplast™ is a knitted product. Fibracol ™ (Johnson & Johnson Medical, Arlington , Texas, USA) is a combination of collagen and calci um algi nate. Collagen, which is the mai n component of skin and connective ti ssue,can encourage wound healing by providing a framework fo r newly fo rmed ti ssue. Kaltostat can absorb protease (- 4%) into the intersti tial spaces between the fibres of the dressing. The proteases, if present in wou nd, can be detrimental to the wound recovery.

An alginate fibre made by Briston-Mayer Squibb (World Patent 96 02283) can abso rb proteinaceous material into the fib re structure, rather than absorbing into interstitial spaces. So, it can absorb more amount of protease6°.Few other products are Curasorb (Kendall Company), Melgisorb (Mol nl ycke Health Care), Orisorb (Orion Medical Product) , Algiderm (Bard Medical Division, Georgia, USA), Seasorb (Coloplast Swean), Cutinova ® (Beiersdorf-Jobst),3M Tegagen HG (Hi gh Gelling) alginate dress ing, 3M Tegagen HI (H igh Integrity) alginate dress ing and Dermastat calcium algi nate dress ing (Derma Sciences, Inc.) . Arglaes (Med ici ne Industries, Inc.) utili zes ionic sil ver in a patented controlled release polymer film to prevent infection by fo rming an effecti ve an timicrobial balTier. The Kendall Company, Mansfield, USA, presented a process to prepare an alginate wound dress ing without any additive. The dressing is said to ex hibit desired haemostatic properties. Generally , algi nate fibre dressi ngs become weak and hydrocollo idal in nature when applied upon an ox idating wound. SO,a secondary dressing becomes essential. In the World Patent 96 01659, the Bristol-Myers Squibb presented6 1 a pressure- sensitive, auto-adhes ive and highly-absorbent algi nate dressing. One side of the pad is coated with a water-based adhes ive whi ch is pressure sensitive. Such a dressing has the advantages that separate dressings need not be used to secure the auto-adhesive dressings. The auto-adhesive dressings also can be cut to fit any irregular type of wound.

But some of the alginate dress ings have poor integrity when dry, hence difficult to handle. Some

GHOSH & JASSAL: USE OF POLYSACCHARIDE FIBR ES FOR MODERN WOUND DRESSINGS 441

dressings tend to shed fibres . Known alginate gels are amorphous materials, which are difficult to handle. Research should be done to provide alginate gels with improved mechanical properti es. Reaction between free Ca2

+ and alginate is so rapid that the introduction of sufficient Ca2

+ to make strong gel, with a distribution throughout the whole volume, may be a problem because shearing would breakdown the rapidly formed gel network. Special sk ill is required to apply these dressings to the wound.

5 Chitin Chitin has long been known as being able to

accelerate wound healing process. It has been shown62

that by applying chitin dressings, the wound healing process can be accelerated by up to 75 %. Chitin is one of the most abundant natural polysaccharides existing widely in in sects exoskeletons or cuticles of many in vertebrates, cell walls of most fungi, and cru stacean shell sC>Hrl such as lobsters and crabs. Chitins are homo­polymer of ~(l-4) linked N-acetyl-D-glucosamine. The structure of chitin is similar to that of cellulose (Fig. 3).Onl y hydroxy l group at C-2 position of cellulose is replaced by an acetamide group. Chitin is a linear polysaccharide wi th ~-I A-bonded 2-acetoamide-2-deoxy-D-glucose(N- acetyl- D-glucosamine).

5.1 Processing and Fibre Preparation

Chitin is obtained as a byproduct of sea food indus­try. The shells of crabs, shrimps, prawns and lobsters coming from the peeling machines in canning factories are presently used for large-scale production of chitin. The processing of crustacean shell s mainly involves the removal of proteins and the di ssolution of calcium car­bonate, which is present in crab shell s in high concen­tration. The deprotinisation is done under alkaline con­ditions and the demineralization is done by HCI to re­move the minerals like CaC03 to produce pure chitin commercially. Lipids and pigments may also be ex­tracted. Depending on the alkali concentration,some soluble glycans are removedos. The resulting chitin is deacetylated60 in 40% NaOH at 120°C for 1-3 h. This treatment produces 70% deacetylated chitosan.

The dry mass of shell waste typically contains about 15-25% chitin. Chitins isolated di ffers from each other in many respects- degree of acetylation (-0.9), element analysis (w ith N-content close to 7%), N/C ratio (0.146 for fully acetylated chitin or 0.153 for degree of acetylation 0.8), molecular size, monodispersity , etc. Average molecular weight fo r commerci al chitin is 0.5-1 Mda.

H H

tbi0 HH~?~

° ~T / '0

CH20H I ° H

(0)

CH3 I

:ttlfHH r~

HO . NH

o 0

CH2011 I ° H

(b)

Fig. 3--Sl ruclures or (a) cellul ose and (b) chilin

Chitin is difficult to di sso lve due to its physical and chemical nature. Although a large number of so lvents such as dil HCI , dil H2S04• trichloroacetic ac id, formic ac id , alcohol and hydrocarbon have been used to dissolve chitin, the dissolution process is often complicated and impractica l. High chemical reagent stability and so lvent stabili ty of chitin is due to the ex istence of different functional groups such as an acetamide group at C-2 carbon, secondary alcoho li c hydroxy l group at C-3 carbon, and primary alcoholic hydroxy l group at C-6 carbon. Due to the H-bond between the acetamide group at C-2 carbon and a hydroxy l group at C-6 carbon, a strong crystalline structure is formed64

. Chitin can be dissolved in cone. HCI I H2S0~ but its molecular weight is remarkably reduced due to hydrolysis of I A-glucos ide bonds .

In 1980s, due to the extensive development on the so lvent system, a new solvent for the chitin was developed which offers the opportunity for the easy processing of chitin into fibres. By treat ing chitin first with p-toulene sulphonic ac id in isopropanol, ch itin may be eas il y dissolved in dimethylacetamide (DMAc) containing a small amount of lith ium chloride. The chitin solution in DMAc-LiCI can be extruded into a coagulation bath of either water or methanol solution to form fibres67

. Formic ac id­dichloroacctic acid6~ , NMP-LiCl6'J and hexaflu oro­isopropanol70 can also disso lve chitin.

Chitin fibre was first reported7 1 in 1926, when the German Scientists succeeded in making an arti ficial silk that resembled the texture of the natural silk . Chitin fibres are usually made by wet sp inning or dry­jet wet spinning process67.Chitin fibre can also be spun from a dope consisting of 3 parts of ch itin , 50 parts of trich loroaceti c acid and 50 parts of

442 INDIAN J. FIBRE TEXT. RES., DECEMBER 2002

dicl oromethane72. Chitin solution in DM Ac-LiCi were

used for spinning 6 , . .un fibres, whi ch were cut to various lengths and sedi mented to form a thin mat. Nonwoven fabri cs have also been manufac tured and used fo r wound dressings73

.

One of the methods of preparation of chitin fibre66

is as foll ows. Chitin powder is ground to 100 mesh, treated in IN HCI for I h at 4°C, heated to 90°C and treated at thi s temperature fo r 3 h in 0.3% NaOH solution to remove calcium and protein. Then it is rin sed repeatedl y, followed by drying.The resultant chitin is di ssolved in a dimeth yl acetamide to obtain a solu tion having viscosity 256 cP at 30°C. After filtration, the dope is transported fro m a charged tank under pressure by a gear pump to a nozzle (diameter 0.06 mm, 200 holes) and ex truded into butanol at 60°C at a rate of 2.2 g/min. The resultant strand is rinsed wi th water and dri ed to obtain a filament of 0.74 dtex, with a strength of 2.8 g/den.

The research group of the Briti sh Textile Technology Group(BTTG) patented74

.77 methods of

mak ing chitin-based fibrous dress ing fro m microfun gi Micor II/ll cedo. The resulting mi crofungal fi bres are differe nt from normal spun fibres. They have sli ghtl y branched and irregular structures. The fibres are very brittle when dried. Therefore, a pl asticizer must be associated and the dress ing can be prepared by wet­laid mat preparati on method by mi xing with other fibres to give mechani ca l strength.

A research group at the Uni versity of Leeds spun fi bres from another ch i ti n deri vati ve 78 ,

dibutyrylchitin. This deri vati ve was prepared by treatment of krill chitin with butyri c anhyd ride in the presence of perchl oric ac id as a catalyst.

5.2 Application as Wound Dressing

Chitin and so me regenerated chitins, once applied to a wound, are slowly hydrolysed and disappear after three months. Jt is believed to stimulate Iysozy me­pos itive ce ll s in the center of a wound. Lysozy me would hydrol yse chitin to oli gochitin , whi ch would hydrolyse to N-acetyl glucosamine under the acti on of N-acetyl glucosaminidase79

. Chitin is similar in char­acteri stics to glycosamino glycan fo und in skin be­cause the repeat unit of chitin (i.e N-acetyl­gluoxamine) occurs in hyaluronic ac id and is respon­sible fo r the formati on of fi brous networks fo r protein attachment during wound hea ling. Successful chitin surgica l dressi ng has been reportedxo.XJ

. A product named Beschitin W has been marketed by Morihita Co. , Japan, whi ch is made up of chitin fro m crab

H H

01kffo" H CH20H ,0 HO

H

o H

Fig. 4--S lruclure or chilosan

shell. It has been shown that Beschitin W is much better than collagen membrane on pig ski n in terms of air permeability and water absorpti on abilit/ 4

.x5

. It has also been show n that chitin membrane has a affin­ity for skin surfacex6.xx. Chitin seems to inhibit fibro­bl ast (res ponsible fo r scarring) and thus allows for

I . . 89·91 N f' b . norma ti ssue regeneration . onwoven a rI CS

made from chitin are now used in Japan as burn and wound dress ing because of the hemostatic and wound healing abili ty . When used as a coating on biomed ica l materi als such as suture, chitin and chitosan show speeding healing process. Chitin sutures res ist attack in bil e, urine and pancreati c juice, whi ch are prob lem substances for other absorbable sutures'!::: .

6 Chitosan Chitosan is the deacetylated deri va tive of chitin

th at means it is a poly [ ~ - ( 1-4)-2 - ami no- 2-deoxy-D­

glucopyranose] (Fig. 4). This polycati onic biopolymer can be obtained fro m chitin and from fun gi eas il y cultured on simple nutrients. So, chitosan products can become independent of the conventi onal shell fish and shrimp industry waste. But the food industry waste is economica ll y more feas ible, specially when it includes the recovery of carotenoids. The shell s contain considerable quantities of aSlaxanthin , a carotenoid that so fa r has not been sy nthesi zed and is marketed as a fish food additi ve in aquac ultu re , speciall y for Salmon66

. Some fungi studi ed are Absidia blakesleeal1a and coert/lea'!] , Muco r ro[{.\'ii9~, GOllgrone/la butleri, Rhizopus oryzae<J5, CheanepllOl'O cllcurbitarul11, Mortierella isabelilla and Mycosphaere/la pil1odes96

.

6.1 Processing a nd Fibre Preparation

Deacety lation of chitin to produce chi tosan ca n be done by the process sequence shown in Scheme I.

To produce I kg of 70% deacetylated ch itosan from shrimp shell s, 6.3 kg of HCI and 1.8 kg of NaOH are req uired in addition to nitrogen, process water (0.5 tonnes) and cooling water (0.9 tonnes)66. NaO H concentrati on is kept at 40-50% and resiclence time of around 2 h is used. Highly pure chitosan is produced by disso lving it in ac id and remov ing the in so luble impuriti es by fil trat ion. Then chitosan is prec ipitated

GHOS H & JASSAL: USE OF POLYSACCHARIDE FIBRES FOR MODERN WOUND DR ESSINGS 443

CrUS(;1ccam shell

~ Al kali

Prote in, Aci d, Amine +-------- Dcprotcinari t1 n

~ A.,iet

Ocmlnc.."1l1isation

~AlkaJi IJ yd1"o l} tlc dcacc::ylatkJ!l

• G l i.l :uin~

Chilusan p" wdcr

~ Or;ranic acid

tv[i>:ing

chilosnl cid blend

(5clf diss clving)

Dissolu lion

~ Fillration

~ Precipitniton and d"hyumtion

~ Highly pure: c. hitos:n

Scheme I- Preparation of chitosan

by increasin g pH of the solution. Chitosans have N­content hi gher th an 7% and degree of acetylation lower th an 0.4.

In contrast to chi tin, chitosan has much better solubility due to the ease of fo rming ammonium salts is aqueous dilute ac id solution, such as acetic ac id . The preparati on of aqueous chiotsan solution in acetic

. d f" d b R' b 97 98 S I . d aC I was lrst reporte y Ig Y . . ome ot leI' aCI s also can be used, like formi c ac id , 10% citric ac id , py ru vic ac id and lactic ac id . Chitosan can be eas il y dissolved in aqueous so lution of almost all organic and inorganic ac ids. Chitosan fibres can be made by first dissolving it into an aqueous ac idic solution and then extruding the solution th rough fine holes into a coagul ati on ba th of a dilute alkali solution.Chitosan prec ipitates out in the fo rm of a fil ament whi ch can be washed, stretched and dried to fo rm fibres for producti on of wound dressing99. Regenerated chitin powders, chi tin nonwoven fabri cs, porous beads, gel­ro rming lyophili zed soft fl eeces, gauzes, laminated sheets and also chitin/chitosan in assoc iation with other polymers such as cellulose, collagen, keratin , chondroitin sulphate, pol yurethane, polyester, polytetrafluoroethylene are used as wound dress ings.

6.2 Wound Dressing Application

. b' d d bl . 100·106 Chitosan IS 10 egra a e, non-tox Ic to animals (in mi ce, LDso is more than 16 g/kg, i.e higher than sucrose) and human. The LDso va lue is the amount of solid or liquid materi al that it rakes to kill 50% of test animals in one dose (50% leth al concentration).

Ch itosan (degree of acetylation, 0.7) was fo und to be the most effecti ve immunomodul ator for the ac tivati on of non-specific host resistance aga inst bacterial and viral infecti on in mice. This effect was partl y med iated by stimulating cytoc idal acti vities of peritoneal macrophases and NK cell s lo7 .The antimicrobial fun ction of chitosan is achi eved as it suppresses the metaboli c acti vity of bac teri a by blocking the nutrient permeati on through cell wa ll , inacti vating enzy mes, imparting phys ico-chemical stress on the cell wall and forming polyelectrolyte complexes with anioni c spec ies in the wa ll. Chi tosan has been reported to be bioresorbable lox. 111 when used in human and animals.

Chemical and biochemical reacti vity of chi tosan and parti all y ace tylated chitosan is hi gher than that of chitin because chitosan has free primary groups distributed regul arl y in the chain . They can be app lied

d . , d dl' 11'111 as rug carn ers In rug e Ivery systems -. ' . Oligomers of chitin and chitosan have been reported to ex hibit some phys iological acti viti es, such as antitumour and antimicrob i a l l l ~.II5. Due to the biodegradability, low tox Icity and good bioco mpatibility, chitosan and modified chi tosans have stimulated intensive research in med ical field to

h f d· I I" 116 Ch' searc or new me Ica app Icatl ons. Itosan ex hibits hemostatic ac ti vity when used as a hi gh molecul ar weight solid . Water-so lu ble depolymerized chitosan and o ligomers have no th ro mbogenic activity. Chitosan has been explored as a modul ator of wound healingI1 7. 118. It has been indicated that chitosan has the ability to form a coagululll on contact with erythrocytes, even in heparini zed blood, defibrinated blood and washed red blood cel ls l16. Chitosan may prove to be useful as an aid to hemostas is in patients with coagul opathies . Li ngual bleeding times are decreased in rabbits without

. fOf 119 K' I PO d I apparent systemi c e ect . 1m et (l . - reporte t lat a wound-co veri ng materi al composed of polye lectro lyte complexes of chitosan and sul fonated chitosan hastened wound healing and yielded a 'good­looking' skin surface. This materi al was fo und to be effecti ve in regenerating skin ti ssue of wound area. It

444 INDIAN J. FIBRE TEXT. RES., DECEMBER 2002

was observed that wound healing is accelerated by the oligomers of degraded chitosan by ti ssue enzy me.

The effect of chitosan on wound healing in patients undergoing plastic surgery was noted by Muzzarelli et al.121

• They developed N-carboxybutyl derivative of chitosan dressing for treating the plastic surgery donor site. The solution of N-carboxybutyl ehitosan was dial ysed and dried to make soft f"1exible pad. They also reported that the surgical sites treated with chitosan ex hi bited better hi sto-architecture and vascularity compared with untreated controls. There were no inflammatory ce ll s at the dermal layers of ti ssue treated with chitosan , and fewer proliferation of malpigti an layer was reported at epidermal level. III vit ro studies have further clarified the contribution of chitosan to wound healing through activation of its fibrogenic mediators slIch as growth factors and cytokines 122-117.

This increased ex pression of growth factors enhanced fibroblasti c act ivity and promoted fibrous tissue sy nthes is. The ability of chitosan to promote wound healing may also be due to its tendency to form polyelectrolyte complexes wi th polyanion heparin 118. 1 2~ which possesses anti -coagulant as well as anGioaenic

O t· 130. 13 1 TI ' I I I I b b?I ' pr per les . liS mo ecu e en lances anc sta I Izes the fibrob last growth factorU2

·m . By forming a

complex with heparin and acting to prolong the half­li fe of growth fact ors, chitosan promotes ti ssue growth and wound healing.

Recently, chitosan has been proposed to serve as a non-protein matrix for three-dimensional ti ssue growth . Chitosan could prov ide the biologica l primer for ce ll ti ssue prol i feration and reconstruction 1)-' .

Muzzare lli m prepared the chitosan derivat ive 5-methylpyrrolidone chitosan, which was made by a seri es of chemical reactions. This polymer is compatible with other polymer solutions, including gelatin , polyvinyl alcohol, poly(vinyl py rro lidone) and hya luronic acid. It is claimed th at thi s polymer can be used for hea ling of wounded meni sca l tissues, healing of decubitu s ulcers and depress ion of capsule formati on around prostheses. Some wound dress ing sampl es were prepared from the aqueous solution of 5-methylpyrrolidone chitosan, which was dialyzed and laminated between stainl ess steel plates and freeze dried to yield fl eece. Dressings based on 5-methylpyrrolidone ch itosan can be fabricated into many different forms, such as filament s, nonwoven fab ri cs, etc. Once app lied to a wound , 5-methyl­pyrrol idone chi tosan becomes immediately ava i lable in the form of oli go mers produced under the action of lysozyme.

Sparkes and Murray 136 developed a surgical dressing made of chitosan-gelatin complex . Chitosan is dissolved in water in presence of sui table acid to maintain pH 2-3 , followed by add ition of gelatin di ssolved in water. Weight ratio of chitosan to gelatin ranges from 3: 1 to I :3 . Glycerol and sorbitol are used as plastici zer. Dress ing film was cast from thi s solution on a fl at plate and dri ed at room temperature. They claimed that, in contrast to conventi onal biolog ical dress ings, thi s experimental dress ing di splayed excellent adhesion to subcutaneo us fa t. A recent study 137 reports asymmetric chitosan membrane for the use as wound dressing whi ch consists of a dense sk in surface on top layer support ed by a macroporous sponge-like sublayer. This shows excellent oxygen permeability and con trolled evapora ti ve water loss along with good antibacterial properties, indicating that asy metri c chitosan membrane mi ght be a potenti al wound dress i ng material.

7 Modified Cellulosic Fibres Cellulose is the most abundant naturallv occurrin a _ b

polymer which is rigid , hi ghly crystalline and very difficult to solubili se. Therefore, nati ve cellulose form is mod ifi ed to get the fl ex ibility and sol ubility for biomedical applica ti ons. Derivatives of cell ul oses like hydrox ypropy Imeth y I ce ll u lose, carbox y meth y I cellulose and hydroxy methyl cellulose are approved for dermal contact. In the treatment of chronic and ex uding wounds , the materi al used for dress ing should have fluid absorbency and retention fo r long time, and should not damage the newly fo rmed ti ssues when removed. Sodium carboxymeth yl ce llulose (Fig.5) forms soft gel above the wound and meet these criteria.

Sodium carboxymethyl ated cellulose fi re can be prepared as show n in Scheme 2. The degree of substitution is con tro ll ed by concentrat ion of mono­chl oroaceti c ac id , reaction ti me and temperature I.1X .

Co mmerc ial products generall y have the degree of substitution between 0.65 and 1.45. Water-so luble sodium carboxymethyl cellulose fibres prepared by

,JS1'J ! e + l Hr~-O No

o Fig. 5- SlruclUrc of crbox ylllcl hy l cc ll ulosc

GHOSH & JASSAL: USE OF POLYSACCHARIDE FIBRES FOR MODERN WOUND DR ESS INGS 445

Cdlulosc (from wood pulp, COlloll li nlzrs)

t Slurried in aqueous organic solvent (waTer-propanc,l !)r aceTone) t Strong NaOH

NaCI, Na -aeel"le .. <1111-----

Swollen alkali fu nn

~ MonochlOfO"cctic acid

NaCMC

~ Glacial ;ICCtiC acid

NCUlwliz.e.d produci

Sodium carbox11ethYI cell ulose

Schcmc 2-Preparation o f carboxymeth y l ce llulosc

wet spinning method have poor tensile strength and are too readily dispersibl e for use in wound dress in g. A novel method of preparing thi s fibre has been

I'~ .. I " I 140141 I I I reported J . The cll l11 ca tna s · lave a so s 10wn that the nonwoven wound dressing made from thi s fibre results in extended wear times and fewer dress ing change due to the ability of the fibre to control fl uid flow by gel blocking.

A wound dressing made from cellulose ester and a solvent is patented by Ce lanese Acetate of Charlotte, North Carolin a, USA (U S Pat 5 89 1 075) whi ch releases acet ic ac id in a controlled manner (4-6 mg/day) by hydrolysis reaction at body temperature. Organic cel lulose esters used in the dress ing can incl ude cellulose acetate, cellulose propionate, cellulose butyrate, cellulose acetate propionate, cellulose acetate butyrate and cellulose propionate butyrate. Solvents may be glycero l triacetate, trimethylene glyco l diacetate and glycol monoeth yl ether acetateI4~. These can be used in the form of microporous fi lm or staple fibre/fil ament to form a woven or nonwoven fabric.

Johnson & Johnson Medical, Arlington , Texas, USA, patented (WP 98 00 I 80) the use of ox idi zed cellulose along with structural protein like coll agen , to prepare the dressing for chronic wound treatment like venous, decubiti s ulcer (a lso known as bedsores, pressure sores and pressure wounds) and diabeti c ulcer.Oxidati on of cellulose is done by dinitrogen tetrox ide. Ox idi zed ce ll u lose is biodegradab le and bioabsorbable under phys iolog ical condition s. The company claimed th at the dress in g has an ab ility to bind the arowth factors and retain them at the wound

~

site rather than being washed away with wound

-0 I

ttCH20H

OH H

HO 0,

H OH ~CH20 H

OH H HO 0-

H OH

Fig. 6-- Structurc of dcx tran

ex udates. Gradual breakdown of ox idi zed cellulose at

Phys iolooical pH results in the gradual release of ~ 141

growth facto rs back to the wound . ~ Permanent fixati on of biopolymers on cellulos ics can be achieved by application of cyan uri c chl oride or other bifunctional spacer molecul es into so lutions of the biopol ymer at temperatu re of O-IOcC and the subsequent use of the resulting solution without isolation of the modified biopolymer for appli ca ti on onto web or nonwovenl44 .

8 Dext.-an Dextran is the bacterial homopolysaccharide

derived from cultures of Lellconostoc lIIesenteroides in prese nce of sucrose.

8.1 Structure

Dextran is ( I ,6)- linked a- D-g lucan with the side chain attached to 0-3 of the backbone chain uni ts (Fi g. 6). The branchin g, frequency and the branch lenoth were shown to be dependent on the te;perature at wh ich the dex tran is sy nthes ized l45 and

. I I'd 146 the molec ular weight of the po ysacc 1an e Dex tran adopts a ribbon like conformati on with the unit cell contai ning two anti-parall el chains , each of the two D-glucopyranoxy l units.

Most of the phys ical properties of dex tran fracti on and associated biomedical properti es are dependent upon the molecular weight distributi on of dex tran . Even at hi gh molec ul ar weight , dex trans are readil y soluble in water and electrolyte solution.

8.2 Application

Dextran can be degraded in vivo by the enzymes present in mammalian ti ssue. In fibrinolysi s, dextran

446 INDIAN 1. FIBRE TEXT. RES., DECEMBER 2002

accelerates the polymerization of fibrin and influences the structure of the fibrin clot with the di ameter of the fibrin fibres being broader when dex tran is present l47. But the major problem of using dex tran in wound dress ing is its hi gh solubility. To reduce solubility for use in wound management, an emulsion pol y­meri zation of dex tran is crosslinked with epichl oro­hydrin , resulting in a three-dimensional lattice polymer that can be processed in the form of small spherical beads, which are water- swell able and capable of absorbing large quantity of fluid s in ex uding wounds 1~ 8 . 1 ~<). This hydrolyti cally labil e non­tox ic crosslinked dex tran is also formed by treating water-soluble non-cross linked polysaccharide with cyanogens bromide in aqueous alka line so lution, whi ch is the disperse phase of water-in-o il di spersion (US Pat 5 549 908). The crosslinked pol ysaccharide consists of polysaccharide chains and cross linking groups which are imido carbonate groups, carbonate groups or their mi xture.

The beads or microspheres may be formed into the wound dress ing which includes a blend of the microspheres and a hydrophobic adhes ive matri x materi al on a waterproof backing sheetlso. Highly hydrophili c dex tran-polymer beads poured into secreting wounds to absorb wound ex udates can act as a debriding agent ; it prevents cru st fo rmati on. Beads used in treatment of skin lesions are reported to absorb 4 ml/g of wound ex udates fro m infected secreting wounds with an associated reducti on in the time required fo r healing lSI . The crosslinked beads have also been reported to help in wound healing by stimul ating macrophages and inducing peritoneal ex udate l52 .

9 Hyaluronate Hyaluroni c ac id is one of the major components of

mam malian extracellul ar matri x. It is widely di stributed in animal or bac teri al organi sms, mainl y present in sy nov ial fluid , vitreous humor, umbeli cal cord or in streptococus bac teri a.

9.1 Structure

It is glycosaminog lycan , whi ch co nsists of alternating units of N-acetyl g lucosamine and glucuronic ac id res idues, where the glycosidic bond is a ( 1,3) -1 inkage between the glucopyranosy luronic ac id and the 2-acetamido-2-deoxy-glucopyranosy l ac id res idue (Fig. 7). The molecul ar weight can be of the order of one million dalton , depending on the onglIl .

Fig. 7- Structure or hyaluroni c ac id

9.2 Application

The large hya luronate polysaccharide molecules are water solu ble, resulting in solutions whi ch are hi ghl y viscous even at low concentrati on. It is capab le of interacting with a wide range of biomolec ules i ncl uding ti ssue components, pro tei n, proteoglycons and growth factors. In the dissolved state, hyalu ronate has vi sco-elasti c and hydrating properti es wh ich have been used in vari ous biomedi cal appli cations, li ke

I h I . 151 . f l ' . op lt a mlc surgery " ,cosmeti c ormu atlon or VISCO-suppl ementation 1 5~ to improve joint movement.

It has been reported l55 that introducing hyalu ronic ac id/hyaluronate into infected woun ds can accelerate the wound repair and healing process by ac ting as bacteri ostat. Its limi tations in wound care prod uct are its solubility in water, rapid resorption and short res idence time in ti ssue. To increase its usability it is chemicall y mod ified by various approaches. It can be crosslinked with carbodiimides or epichlorohydrin to fo rm insoluble three-dimensional networks. The polymer has been modified by esteri fication process l56, resulting in a new class of highly biocompatible polysaccharides that can be processed by ex trusion, phase inversion technique and spray drying to obtain several forms as fibres, fi lms, sponge, microspheres, etc . Recently, este ri fication of free carboxy l groups of the glucuronic ac id residues in the polysacchari de chain has been reported l.'i7. The mostly used ester derivatives of hyaluroni c acid are ethyl and benzy l derivati ves with high degree of esteri ficati on. The benzyl ester prod uct ( 100 % esteri ficati on) absorbs water to give 40% increase in weig l and ethyl ester derivative (100% esteri ficati on) absorbs water to give a 200% increase in weight. As the degree of esterificati on is decreased, the waler absorbency increases until the point is reached at which the material disso lves. Therefore, by contro lling the degree of esterification,materials can be produced which will be di ssolved rapidly or remain as semi - solid hydrogel

d " I . . d lS5 on woun .or ong time peno . A new semi-synthetic biomate ri al based on

hyaluroni c ac id has provided a support suitable fo r the transfer to the graft site of cultured autologous or

GHOSH & JASSA L: USE OF POLYSACCHARIDE FIBRES FOR MODERN WOUND DR ESSINGS 447

heterologous keratinocy tes. M embranes of totally esterified benzyl derivative of hyaluroic ac id carry ing holes (6000/cm2) of 40 Ilm in diameter, when used as support of keratinocyte cu ltures, exhibited an earl y growth of baseloid cell s to fill the pores in a short timel5X . Thi s characteristic suggests the clini ca l use of these membranes as carriers of actively proliferating

. f' k ' 159 R I h I Ul1lts 0 ' eratlonocytes · . ecent y, ya uronate-I . I . d bib' . 1160 a glllate ge IS reporte to e a nove lomatena

which can be used in wound care.

10 Pectin Pectins are complex heteropol ysaccharides that

occur in ce ll wall and intracellular spaces of higher plant ti ssues. Pectins of industrial grade are obta ined generall y from citrus peel.

Pect ins consist of up to 80% a ( 1-4) linked galacturonic acids which are partiall y esterified with methano l and neutral sugar. L-Rhamnose connected with a( I-2) linkages is responsible for branching in the polysaccharide backbonel61 . The residual galacturonic ac id content and percentage of esterifi cat ion with methoxy groups will determine the abil ity of pectin to form highly hydrated gels for use in dermal applica ti on.

11 (1-3) ~-D- Glucans Lelbovich and Oanonl62 reported that topi ca l

appli cation of glucan from yeast results in rap id wound healing. They also reported that the rate of repair is faster for glucan than for the pol ysaccharides carrageenan, levan, inulin, dextran and starch . Thi s is due to the induced reti culo-endothetial system stimulati on, i .e. stimulati on of Iympho-reticul ar ce ll s of mammalian defense system including macrophages, endothelial and reti culum cell s. Therefore, the resistance aga inst infecti on IS

increased; inhibition to tumor growth and improvement in wound hea ling is ex pected.

Lentinan is a (J -3) B-D-g lucan with ( 1-6) ~-D­glucopyranos ide branches (Fig.8). It has anti-tumor acti vity in allogen ic, syngenic and auto-chthonous primary hosts, suppressing chemica l and viral oncogenes is and reportedly preventing cancer recurrence or metastasis after surgical intervention.

12 Some Other Products Courtau lds Speciality Fibres (Coventry) have

introduced a fibre named ' Hydrocel ' as an alternative to alginate in wound dressing appl icati on. It is carboxymeth yl ce llulose product chemicall y

Fig. 8-- Structure of lentinan

converted from Iyocell. It gels on contact with the wound fluid to prov ide a non-adherent moist environment. Convatec, UK, has taken up the manufacture of the gel, which they named as ' Aquagel '.

Chondroprotec® (The Hymed Group Corporati on , Beth lehem), a topica l wound dressing made from polysul fated glycosamino glycan, can be used for partial and fu ll thickness wound, trauma injuries, I " and 21lL1 degree burn and pressure ulcer. Glycosamino glycan supports and enhances the connective tissue matrix. These compounds have become beneficial in management of chronic and acute wound. Pol ysulphated glycosamine glycan rehydrate dry wounds, maintain moist hea ling environment and protect the wounds from ti ssue traumaI 6:1.16~ . Chondroprotec is a steril e 10 ml solution containing 1000 mg of po lysulfated glycosamino glycan . NaOH or HCI is added to adjust pH to 6.S-6.7.

Maxorb(Medline Industries Inc.) is a nonwoven dressing made from alginate and carboxy methy l ce llulose fibre in combination, which prov ides a moist healing environment. Sterigel®, produced from branan ferulate, is a cross linked gel extracted from

b . Ik I' 161 corn ran USI ng a a I '.

13 Conclusions Hi stori ca ll y, the so le function of wound dressing

was just to provide a cover over the wound , but in the recent years due to the innovat ion both in medical procedures and tex ti Ie sciences, preparati on of wound dressing has become a spec iali zed high technolog ical process. The idea of moist heal i ng, use of biocompat ible and ' tai lor made' dressings have brought a revo lution in wound management. Trad itional cotton dress ings are di sadvantageous because duri ng hea l i ng small fib rous elements protruding from the dress ing are usuall y trapped in the pores of the newly formed tissues which make their removal distress ing to the patients. Nonwoven

448 INDIAN J. FIBRE TEXT. RES., DECEMB ER 2002

fabrics made of chitin are being used as burn and wound dressing because of the hemostatic and wound healing ability of chitin . Calcium alginate dress ings have good absorpti ve properties for both blood and wound ex udates and are able to keep moist healing environment with desired non- adherent property. Various other polysaccharides such as hyaluronate, dex tran and modi fied cellulosic fibres are being used for wound dressing, but these products still are at early stages of research.

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