BIOMATERIALS GROUP

Skin is a vital organ, in the sense that loss of substantial fraction of its mass immediately threatens the life of the individual. Such loss can result suddenly, either from fire or from a mechanical accident. Loss of skin can also occur in a chronic manner, as in skin ulcers. Irrespective of time scale over which skin loss is incurred, the resulting deficit is considered life threatening primarily for two reasons: skin is a barrier to loss of water and electrolytes from the body, and it is a barrier to infection from airborne organisms. A substantial deficit in the integrity of skin leaves the individual unprotected either from shock, the result of excessive loss of water and electrolyte, or from sepsis, the result of a massive systemic infection. It has been reported that burns alone account for 2,150,000 procedures every year in the United States. Of, these, 150,000 refer to individuals who are hospitalized, and as many as 10,000 die.

Prompt replacement of the integrity of the skin is a corner-stone of therapy, but lack of available natural skin makes this an almost impossible task for those large wounds or burns. The modern search for a suitable skin substitute has been under way since the 1940s, with steady progress as the wound healing and the functions and properties of the skin became better understood.

In this term-paper, functions and properties of skin, principles of wound healing, types and properties of wound dressings and their applications are reviewed. Some recent studies about wound dressings are also examined.

The skin is considered the largest organ of the body and has many different functions. The skin functions in thermoregulation, protection, metabolic functions and sensation. The skin is divided into two main regions, the epidermis, and the dermis, each providing a distinct role in the overall function of the skin. The dermis is attached to an underlying hypodermis, also called subcutaneous connective tissue, which stores adipose tissue and is recognized as the superficial fascia of gross anatomy.

There are five major functions of the skin: protection, temperature regulation, sensory perception, excretion, and vitamin production.

Protection: The skin provides the body with an airtight and waterproof covering that holds the units of the body in. When unbroken, the skin acts as a barrier to harmful bacteria. The pigment of the color matter, melanin, of the skin screens out certain harmful rays of the sun. The skin minimizes the mechanical injury of underlying structures.

Temperature Regulation: The skin helps the body t regulate its own temperature. When the body surface is cold, blood vessels in the skin contract and force the blood deeper into the body. This prevents the body from losing much heat by radiation. When the body is too warm, the same blood vessels expand and bring more blood to the surface of the skin. This allows the body to lose heat by radiation. Also, the sweat glands pour out perspiration. The perspiration evaporates and since evaporation is a cooling process, the skin is further cooled.

Sensory Perception: Millions of microscopic nerve endings are distributed throughout the skin. These serve as receptors for pain, touch, heat, pressure, position, etc. They are the body’s antennae, keeping it informed of changes in the environment.

Excretion: Sweat is mainly water. Only about one half of one percent consists of other chemicals. They include a small amount of sodium chloride, urea, and lactic acid.

Vitamin Production: Vitamin D_,an essential vitamin, is formed in the body by exposure of the skin to ultraviolet rays, either from the sun or a lamp. After being produced or on the skin, vitamin D is absorbed through the skin and carried to the liver and other organs for us.

The outer skin, epidermis, is made up of numerous cells that are placed side-by-side and arranged one above the other in several layers. The topmost layer (stratum corneum) is composed of dead cells that are continually being worn off. Unlike reptiles that shed their skin all at once, humans shed skin as thin flakes. These flakes are the dead skin that a person often rubs off with a towel after taking a bath or peels off as skin patches after a sunburn. When the skin is exposed to repeated pressure, the dead cells clump together instead of falling off, and a callus or a "corn" is formed. Dandruff is a name given to dead skin cells that have flaked off from the scalp in large amounts. New cells originate in the germinative layer at the bottom of the epidermis. These new cells mature as they move upward in the layers of the epidermis; they become flatter and drier as they are pushed upward and outward by the new cells below them. It takes about a month for every skin cell to die and be replaced.

There are some nerve cells in the epidermis, but there are no blood vessels. The epidermis contains the pigment (granules of material called melanin) that is responsible for the color of our skin, suntan, and freckles.

The dermis, the inner and thicker layer of the skin, lies beneath the epidermis. It is also known as the corium or the "true skin." The surface or upper layer of this dermis is cobbled, ridged, valleyed, and meshes with the pitted undersurface of the epidermis and binds the two together. These ridges are arranged in regular curved rows and are as unique to each individual person as fingerprints. However, these ridges have a more fundamental function. Ducts of sweat glands surface through these ridges to give a nonskid surface to hands and feet and enable us to pick up small objects and do delicate manipulations. Into this upper layer of the dermis come thousands of capillaries, the small blood vessels that bring food and oxygen to the cells and remove waste. This inner layer is strong and elastic, and it contains nerve fibers; receptor organs for sensations of touch, pain, heat and cold, muscular elements, hair follicles, and oil and sweat glands.

Deeper in the dermis are the roots of skin glands and hair, as well as, more blood and lymph vessels, more nerves and larger and tougher fibers.

The sweat glands are the most common ad they are found all over the body. There are about two million sweat glands distributed over the body surface. The most numerous are found on the forehead, face, palms, soles, the groin and the armpits. The sweat gland is a small, tight coil of cells in contacts with a network of capillaries, the smallest blood vessel. Ducts of the gland corkscrew through the epidermis to the skin surface. These glands give off a small amount of waste material, but their most important function is to regulate body heat. As the sweat evaporates, it cools the surface of the body.

The second group of skin glands are the sebaceous glands. These glands produce oils and fats and are about as numerous as the sweat glands. These glands generally open into the hair follicle and give off an oily substance called sebum. This sebum seeps into the hair follicle and works its way to the surface where it spreads a thin film. Its primary function is lubrication for the hairshaft and the horny layers of the skin. The lubricant also helps prevent excessive evaporation and absorption of water and excess heat loss.

In addition, the chemicals in sebum play an important role in maintaining the normal acidity (PH) of the skin. This oil or sebum keeps the skin soft and pliant. It protects the body from water absorption through the skin and excessive evaporation from the skin. Because fat is a poor conductor of heat, the sebum lessens the amount of heat loss from the body’s surface.

The surface of the normal healthy skin is slightly acid in reaction. A change toward alkalinity is thought to increase the susceptibility of skin to fungal infection and other disorders.

Oil glands are distributed almost over the entire body and are the largest in regions of the forehead, face, neck, and chest. However, the palms of the hands and the soles of the feet are poorly greased.

The structure of the hair is similar to that of the outer layer of skin. Just as the epidermis is formed by the cells in its deepest layer, reproducing and pushing the cells which become horny in character, so a hair is developed by pushing a group of cells at its base, pushing upward and in the process becoming keratinized. The part of the hair that is visible is the shaft, whereas that which is embedded in the dermis is the root. The root, together with its covering, forms the hair follicle. At the bottom of the hair follicle is a loop of capillaries enclosed in a connective tissue covering called the hair papilla. The cluster of epithelial cells lying over the papilla are the ones that reproduced and eventually form the hair shaft. As long as these cells remain alive, hair will regenerate even though it will be cut or plucked or otherwise removed.

Skin is a multi-component of cells and macromolecules. The major component of the epidermis is the keratinocyte, which forms overlapping structures held together by desmosomes which provide cell-to-cell adhesion. The dermis is composed largely of extracellular matrix components including collagen, elastin, fibrillin, hyaluronic acid and proteoglycans. Collagen fibers give shape to the skin as well as prevent premature mechanical failure. Elastin fibers composed of fibrillin and elastin, are believed to be responsible for recovery of skin after removal of a mechanical load.

The fibroblast is the cell type which is most prevalent in skin and is responsible for synthesizing and depositing collagen fibres in continiouos networks that form the structurel scaffold. This cell type is also responsible for recognition, removal and turnover of proteins that are damaged or are being recycled.

The mechanical properties of skin are largely a result of the collagen and elastic fibre networks that form a scaffold upon which cells sit. The surface layer of skin which appears creased under visual observation, is normally under bi-axial pretension and pulls taut under normal physiological loads. In areas of the body where skin covers joints, it must be able to double its strength on streching to allow free joint movement. The ability of skin to deform in a plane as well as to maintain its continuity when subject to forces both in the plane and perpendicular to the plane are of utmost importance.

The mechanical properties of skin to a first approximation are a consequence of the collagen and elastic fibre networks present as well as the proteoglycans that are found between neighbouring collagen fibrils. The epidermis contributes very little to these properties except in areas of the body where the epidermis is thick, such as the palms of the hands and the soles of the feet.

The collagen fiber is made up of many fibrils which, in turn, are made up of smaller microfibrils. The microfibrils are made up of molecules of rod-like structure. Three polypeptide chains, wrapped around each other as a triple helix make up the microfibril providing rigidity to the molecule.

Hydroxyproline, an amino acid, comprises 10% of the total amino acid content of collagen, without hydroxyproline no triple helix is formed and the alpha chains are degraded. Vitamin C is essential for the formation of hydroxyproline by the enzyme prolylhydroxylase. Scurvy results from lack of vitamin C and produces many signs of connective tissue abnormalities.

Collagen does not stretch very well since one of its functions is to resist stretching. The ability of collagen to respond to physical stress changes with age and sun damage. It is believed that sunlight in the range of 310 nanometers to 400 nanometers (UVA) is capable of inhibiting the action of the enzyme prolylhydroxylase. There are at least eight major types of collagen and some subtypes as well. For the skin care specialist, Types I and IV are The most important.

Elastin is beginning to command more and more attention from research workers in dermatology, reconstructive surgery and in the basic science disciplines. It is elastin that gives the skin its resiliency and elegant feel. It provides the spring and "snap" to the young face.

Elastin is a fibrous protein that makes up 0.6-2.1% of the dry weight of the skin compared to 72% for collagen. At present only one genetic type of elastin is known. The structure of the elastin molecule has not been defined completely. It is not known if the fibrous protein elastin forms one of the two proteins making up elastic fibers. The elastic fibers are cross-linked by desmosine, a special amino acid that occurs only in elastin. Some investigators suggest it is the desmosine cross-link that provides the spring in the elastin molecule. The other component in the elastic fibers is a microfibrillar structure. These microfibrils surround the elastin molecule and the combination produces the elastic fibers.

Within the dermis, the collagen and elastin are in a fluid matrix called the"ground substance." This matrix consists of water and a class of large molecules (macromolecules) known as proteoglycans.

The dermis reacts instantly to changes in external pressures on the skin by a system that is capable of passing through a phase of almost complete liquid to a phase of almost complete solid. This action is occurs when water binds to macromolecules called proteoglycans. The basic structure of these molecules is a polysaccharide and a protein. The polysaccharides are called glycosaminoglycans. One of these glycosaminoglycans is called hyaluronic acid, another is dermatan sulfate, and together they account for a major portion of the proteoglycans. The total content of these compounds in the skin is only 0.1-0.3% of dry weight of the skin. The proteoglycans serve to maintain water balance in the dermis, to add support for other dermal components and to act as a matrix for cell migration, metabolism and growth.

A typical stress-strain curve for skin is shown in Figure 2.3.2 illustrating an increasing slope with increasing strain. The maximum slope of this plot for individual fibres from rat tail tendon is several thousand MPa. This value is very close to the value of 4000 MPa calculated from viscosity measurements of single collagen molecules. This observation suggests that the stiffness of collageneous tissue is a consequence of the triple helical structure and approaches that of an individual collagen molecule in the dry state. In this state intermolecular and interfibrillar bonding is maximized. When intermolecular and interfibrillar slippage is possible, i.e. in wet tissues, energy is dissipated and as a result of stiffness falls to a level that is far below that of individual collagen molecules. Nature has designed a force dissipating structure that can be somewhat pliant in soft tissues where hydration levels are high, or extremely rigid in bone and dentin where hydration is limited by mineralization.

Other factors that influence the mechanical properties of skin are summarized in Table 2.3.1.

TYPE	Description
Wounds
Acute wound	Caused by trauma or surgery and usually requiring limited local care.
Chronic wound	Takes longer than usual to heal because of underlying conditions, such as pressure, diabetes mellitus, poor circulation, poor nutritional state, immunodeficiencies, or infection.
Full-thickness wound	Tissue destruction extending through the second layer of skin (dermis) to involve subcutaneous tissue under and possibly muscle or bone; tissue can appear snowy white, gray, or brown, with a firm leathery texture.
Laceration	Torn or jagged wound.
Partial-thickness wound	Tissue destruction through the first layer of skin (epidermis), extending into, but not through, the dermis.
Ulcers
Arterial ulcer	Caused by poor blood supply; related to the presence of arterial occlusive disease; symptoms include pain and tissue loss.
Diabetic ulcer	Caused by trauma or pressure secondary to neuropathy or vascular disease related to diabetes mellitus.
Pressure ulcer	Caused by poor blood supply from pressure, this localized tissue damage is also called a decubitus ulcer, bedsore, or pressure sore.
Venous ulcer	Local losses of epidermis and various levels of dermis and subcutaneous tissue, occurring over or near the malleoli of the distal lower extremities; caused by edema and other sequellae of impaired venous return.
Burns (Figure 3.1)
Superficial (first-degree burn)	Damage limited to the epidermis characterized by erythema, hyperemia, tenderness, and pain.
Partial-thickness (second-degree burn)	Superficial to deep partial-thickness wound characterized by large blisters, edema, pain, and wet, weeping, and shiny surface.
Full-thickness (third-degree burn)	Full-thickness wound characterized by deep-red, black, or white appearance; edema; painless nerve ending damage; and exposed subcutaneous fat layer A. partial destruction of the epithelium - remaining small pieces of epithelium, possibly capable of regeneration; B. total destruction of epithelium - no regeneration because of absence of small pieces of epithelium
Fourth degree burn	Damage to far-reaching tissue formations, partial charring - muscles, and tendons affected

In order to reduce the economic, mobidity, and mortality effects of these types of wounds effectively, it is important to develop a systematic approach toward intervention. Repair of these wounds requires both short- and long-term implant systems based on the severity of the wound (partial- or full-thickness wounds). For both systems, the goal for the implant is to increase the rate and quality of healing as compared with passively treated wounds by simulating and/or stimulating epidermel and dermal regeneration.

Repair of skin involves a series of events that are iniated by mechanical, chemical, bacteriological, viral and other traumatic stimuli. (Table 3.1.1)

These events lead to plugging of vascular leaks as well as filling in of tissue defects that arise as aresult of tissue damage. Repair of dermis precedes repair of the epidermis. Dermal repair involves inflammation, immunity, blood clotting, platelet aggregation, fibrinolysis and activation of complement and kinin systems. In the absence of a chronic inflammatory response, dermal wound are repaired through deposition and remodelling of collagen to form scar tissue.

A wound dressing is applied to stop bleeding, absorbs exudates, ease pain, and facilitate epidermal resurfacing. Until the early 1960s the general practice was keep a wound as dry as possible. Then a variety of occlusive and semiocclusive dressings were shown increase the rate of epithelialization by as much as 40 percent. Since the tissue under the dressing remains moist, treatment with these types of dressing has been termed moist wound healing. Generally the type of dressing used in a particular situation is based on its adhesiveness and transparency.

A forerunner of present-day polysaccharide dressings was used by the ancient Egyptians when they applied disaccharides in the form of honey to wounds sustained in battle. Strong solutions of sugars have high osmotic pressures and remove water from damaged tissue. Honey has added advantage of a low pH, thus limiting bacterial growth. Today, sugar is still in use, but insoluble cross-linked dextrans or cross-linked starches as beads are preferred because they readily remove water from the surface of the wound, carrying away bacteria and cellular debris. Iodine can be trapped in starches then released for disinfection upon hydration of the starch.

The role of wound dressings is (1) to replace the function of lost skin, (2) to protect wounds from protein and fluid losses, prevent bacterial invasion, and dissipate mechanical stress (external), an finally (3) to improve and stimulate wound healing. The presence of dead tissues delays wound healing and increase the risk of infection. Initial wound management is the first procedure to be performed before implanting a skin substitute and consists of wound debridement, disinfection by topical antimicrobial agents, and excision of necrotic tissues (more commonly used in burn wounds).

The properties required of skin implants are summarized in Table 4.1. Adherence to wound tissue is one of the main properties required of a skin substitute because this prevents bacterial growth and completely protects the wound. Adherence depends on the conformability, hydrophilicity, and morphological structure of the implant. Complete incorporation of the implant within the tissue is useful if the material is biodegradable. Proper moisture balance is also required to prevent either excess fluid build-up or dessication of repair tissue. The transmissibility of gas and water vapor should be characterized. Other characteristics described in table 4.1 are also necessary.

Wound dressings can be classified into two major categories according to usage as follows:

1. Short term application dressings: These dressings require replacement at regular intervals

2. Long term applications-skin substitutes: They can be further subdivided into:

2.1. Temporary: Applied on fresh ‘partial thickness wounds’ until complete healing is ensured

However, the classification of dressings more frequently used is one based on the nature of its material rather than the mode of application. Based on the type of material used for the preparation of dressing they may be classified as conventional, biological and synthetic dressings. Within each category, the dressings may be further classified into:

3. Island dressing: A dressing that is constructed with a central absorbent portion surrounded by an adhesive portion

These dressing materials are made up of fabric material such as gauze. They provide little or no occlusion and allow evaporation of moisture resulting in a dry desiccated wound bed. Since the conventional dressings had limitations for application on full thickness wounds, research into the development of more advanced wound dressings for the treatment of synthetic and biological dressings.

Biological dressings are derived from natural tissues usually consisting of various formulations and combinations of collagen, elastin and lipid. They are far superior to synthetic dressings in that they

4. prevent bacterial contamination of the wound and hence protect the wound and patient from sepsis;

11. improve quality of healing, inhibit excessive fibroblasts and decrease contraction.

Biological dressings range from allograft, heterografts from pigs, dogs and other species, to embryonic membranes, embryofetus and neonatal skins, films of reconstituted collagen from bovine and other sources, fibrin, cultured epidermal grafts, dermal matrix grafts and cultured dermal matrix composite grafts.

Skin autografts consist of either epidermis and a thin layer of dermis (thin-thickness graft) or epidermis and dermis (thick-thickness graft). They can be expanded (1.5 – 9 times their original size) into a mesh using a device termed a tissue expander. The advantage of using meshed skin is that bacteria, serum and blood are easily washed out through the holes in the mesh. Different skin-graft thicknesses are used for specific surgical applications.

When skin autographs are unavailable and a temporary dressing is needed to cover wound, skin allografts can be used fresh (from living donor) or, more commonly, after thawing (frozen cadaver-skin allografts). Implantation of a skin allograft results in its vascularization; however, if the allograft is used to cover the wound permanently, rejection occurs leaving behind only the collagen of the dermal portion. Allografts are removed and replaced every 2 or 3 days because of the rejection problem and can be expanded as described for skin autografts.

Frozen, irradiated, and dried skin grafts from animals are the most useful xenografts; lyophilized porcine skin can be stored in a dehydrated state at room temperature for long periods of time. Due to rejection reaction these grafts are used in contact with the wound for periods no longer than 2 days. They are replaced at regular intervals with fresh xenograft material. Adherence of a xenograft is similar to that observed with an allograft; however, the graft is more sensitive to enzymatic degradation by enzymes secreted from wound tissues and bacteria compared to allografts.

Amnion is a biological membrane that surrounds the embryo during development and has been used as burn dressing. It is 0.02 – 0.50 mm thick and contains and epithelial cell layer, connective tissue, and fibroblasts. Because of durability problems the amnion is sometimes difficult to handle. In addition, amnion will elicit a rejection response. Normally, amnion is removed three days after grafting because of the problem associated with rejection.

A variety of biological polymers including collagen, fibrin, fibronectin, and hyaluronic acid have been studied as dressings for dermal wounds. Unlike synthetic polymers, which at the very best act as inert coverings for the wound, biological polymers have unique properties that play a role in normal wound healing.

Collagenous Dressings: Porous collagenous materials employ 3-D porous structure (sponge) in the design of a dermal dressing. A three-dimensional structure allows tissue ingrowth into the material and with time the wound tissue and implant can not be separated. The implant is ultimately degraded and is replaced by normal scar tissue. Collagen sponge formation involves freeze-drying a type I collagen acidic treatments such as severe dehydration or irradiation and/or chemical treatments including exposure to carbodiimide, glutaraldehyde, formaldehyde, or diisocyanates. However, the presence of unreacted chemical crosslinking agents or chemicals released by biodegradation at long term into the wound can slow down wound healing.

Alginate Dressings: They are composed of sodium alginate extracted from brown seaweeds. Sodium alginate is water soluble and can be converted to insoluble calcium salt, which is then formed into films. The calcium salt is manufactured as mats for wound dressings, ropes or balls for deeper wounds, and ribbons for packing sinuses. Other dressings include a percentage of sodium alginate to increase the rate of gel formation and useful in treating dry or lightly exuding wounds. The dressings are useful in the management of burns and donor sites, leg ulcers, and infected traumatic wounds. Cast is a major problem with alginate dressings.

Synthetic polymers derived from petroleum products can be easily manufactured using conventional technology into films, fibers, sheets, and sponges. For this reason these materials have received attention as potential wound dressings for deep wounds.

Synthetic polymers have several advantages such as ability to adhere to the wound edges, ability to drape to the wound contour, and ease of use. The major disadvantage is the lack of biological properties such as enhancing wound healing via attraction of cells involved in healing process.

These dressings are used as coverings for deep (full-thickness) burns and skin ulcers. In these applications synthetic polymeric dressings create an inert environment that controls water and heat passage from the wound while preventing bacterial infiltration.

They are homogeneous dressings composed of a polymer sheet coated on one side with an adhesive. They are highly elastomeric and transparent. The most commonly used polymers include polyurethane, polyethylene, polycaprolactone, polytetrafluoroethylene, dimethyl amino ethyl methacrylate. Film dressings are well suited for superficial wounds, but owing to lack of absorbing capacity and impermeable to water vapor and gases cause accumulation of wound fluid beneath the dressing and hence allow leakage of exudates and entry of exogenous bacteria to the wound surface. Therefore, they are not convenient for larger wounds.

The main properties of foams are their conformability, porosity, and insulation and increased adherence to wounds. Polymers such as polyurethane are used to make foam that is stabilized after contact with the wound. These materials are used to fill the wound cavity and when placed in contact with the wound they present a smooth, hydrophilic porous surface. Excess water (exudates composed of wound fluids) and cell debris are absorbed and retained inside the foam. In addition, foams protect the wound from excess pressure. Water vapor and gas transmission can be adjusted by varying the volume fraction of polymer and crosslink density. The one disadvantage of a foam is the low tensile strength and lack of structural integrity.

These are composed of laminates of two or more layers. The outer layer is designed for durability and elasticity and may serve as a rate controller for water evaporation, while the inner layer is designed for maximum adherence and elasticity. Composite dressings may be classified as follows:

Hydrocolloids Dressings: These dressings are compound formulations containing a cocktail of elastomeric adhesive and gelling agents. Carboxy methyl cellulose is the most common absorptive ingredient acting as absorbent for wound fluid.

Granuflex: This material consists of an outer protective layer of polyurethane foam and an inner layer consisting hydrocolloid/polymer complex.

Epigard: This is a composite of an inner layer of reticulated polyurethane laminated to an outer sheet of microporous polytetra fluoro ethylene (PTFE). Adherence, availability, sterility, long shelf life and low cost are its major advantages.

Biobrane: This is a composite of an ultra thin porous membrane of polydimethyl siloxane bonded to an inner nylon mesh.

Hydrogel Sheets: These are sheets of 3-D networks of cross linked hydrophilic polymers. They interact with aqueous solutions. The most commonly used polymers are polyethylene oxide, polyacrylamide and polyvinylpyrolidine. Owing to their unique cooling ability, they may be of great benefit for use as a first aid measure for thermal burns.

Hydrogel Amorphous: These are similar in composition to sheet hydrogels except that the polymer has not been cross linked to form a sheet. They contain small quantities of collagen, alginate or complex carbohydrates. They are unique in their ability to donate moisture to a dry wound eschar and facilitate autolytic debridement in wounds. But owing to the viscosity of the amorphous hydrogel, it may difficult to retain it in the wound bed. However, they exhibit more rapid rate of closure and re-epithelialization as compared with the hydrocolloid wound dressings.

Healing can be altered by changing the wound environment or the wound biological activity. Each of these can significantly affect the progression of healing, the rate of healing, and the type of tissue formed. In addition, if a wound dressing or implant is used the healing can be altered by changing the implant configuration, the implant surface, the implant biological activity, or the implant degradation rate. The goal in virtually all cases is tissue regeneration at the fastest possible rate.

Altering physical parameters such as temperature, humidity, air composition or pressure, and electric or magnetic fields can change the wound macroenvironment. These alterations plus biological response modifiers can also alter the wound microenvironment.

The tissue oxygen level and oxygen gradient are critical factors in the healing process. Oxygen level is often the rate-limiting step in tissue reconstruction. Oxygen is required for various cell functions such as attachment, spreading, and protein production. The gradient is critical in a wound to allow fibroblasts a high oxygen level, at the wound margin, to produce collagen and form the structure for vessels to grow into. The gradient also creates a low oxygen region, in the wound center, to stimulate macrophages to release cytokines that stimulate chemotaxis, mitosis and other steps in the healing process. The diffusion of oxygen from vessels at the wound margin creates the gradient and limits the thickness of tissue that can survive.

The biological activity can be altered by addition of biological response modifiers such as growth factors or cytokines, integrins and extracellular matrix (ECM) molecules. These substances are used to influence cell-cell, cell-matrix, and cell-growth factor interactions in an effort to control cell proliferation, adhesion, migration, uptake, secretion, and differentiation.

Various other biological response modifiers have been incorporated into implants to enhance healing or ingrowth. This includes polymerizable ECM molecules (fibrinogen, albumin, collagen, and hyaluronate) used not only to stimulate cell migration and activity but also to serve as scaffolds and drug delivery systems.

When a wound dressing or implant is used, wound healing can be altered by changing the implant configuration (pore size, porosity, fiber diameter etc.), the implant surface (composition, charge, surface energy, etc.), the implant biochemical activity (incorporation of growth factors or other biological response modifiers), or the implant physical activity (degradation rate and drug delivery rate).

The skin replacement must wet the wound surface, conform to the wound surface in all areas, and adhere in all areas. Without these properties, small air pockets exist where exudative fluid accumulates and bacteria proliferate. The dressing must chemically adhere to the wound bed to avoid proliferation of the granulating layer and therefore control the subsequent contraction and deformity of the wound.

Optimization of implant configuration leads to significant enhancement of regenerative skin healing. Variables such as pore size, percent porosity, fiber diameter, and surface roughness of the matrix determine the speed and completion of ingrowth. Pore size must be large enough to allow blood vessel ingrowth (at least 40 μm). At larger pore sizes, however, the scaffolding effect decreases. The optimal pore size for collagen-based wound dressings is approximately 100 μm.

Since some of these porous structures are fibrous it has also been necessary to examine the effect of fiber diameter and fiber spacing (akin to pore size) on soft tissue ingrowth. In vivo and in vitro studies have shown that increasing fiber diameters (≥50 μm) leads to significant reduction in the chronic inflammatory response. Further, the average fiber spacing requirements are similar to the pore size requirements (40 μm) for vascular ingrowth.

When the system is degradable, the porosity and average pore size change over time.

A number of degradable systems have been studied for use as potential drug delivery/wound dressing systems, including poly(lactic acid) (PLA), collagen and hyaluronic acid and fibrin. Synthetic polymers, such as PLA, are typically made into a performed matrix, which is then placed on the wound and sutured into place. Of these materials, fibrin is the only one with notable adhesive properties, allowing for adhesion to the wound bed, as well as the potential to adhere skin grafts. In open skin wounds, adhesiveness can also decrease the loss of drug delivery matrix due to abrasion of wound coverings and clothes, and provide a uniform contact between the tissue and the drug delivery system.

An ideal drug delivery system should be biocompatible, easily delivered, degradable, allow for control of the drug delivery rate, and should not alter the activity of the drug to be delivered. The natural materials, including collagen, hyaluronic acid, chitosan and fibrin have all been applied topically to wounds. Topical applications that set up in situ eliminate the need for preshaping and measuring an implant prior to application, and allows for easy delivery. Implants used in the skin, as tissue scaffolds, should be degradable to allow for complete skin regeneration. Natural materials are advantageous over synthetic materials because degradation is primarily cell-controlled, allowing for biofeedback control. Further, the degradation by-products are biocompatible.

The mixed results for topical growth factors are most likely due to release of unprotected growth factoring a wound environment filled with proteolytic enzymes, as well as the lack of a scaffold to guide the tissue growth stimulated by the growth factor. Also since healing has been enhanced by continuous dosing, a controlled release system would be more convenient than daily dosing, and more effective in controlling the healing process. A biodegradable controlled release system could serve as a protective reservoir of the growth factor prior to release, provide a constant rate of medication and serve as a tissue regeneration scaffold. In addition, regenerative tissue adhesive scaffolds that degrade primarily due to cellular invasion, such as natural materials, provide biofeedback control of both the degradation and release rate of the growth factor. This means the patient’s own healing rate controls the scaffold regeneration, which also controls the introduction of the growth factor.

A dressing must be supple enough to allow for some underlying movement of the wound but meanwhile it must maintain an even contact with its surface. The dressing must also be durable and allow for easy handling without tearing. It must allow suturing, and be durable enough to cover the wound for the entire healing period. To design a membrane with appropriate modulus of elasticity and tear strength, the dressing may be modeled as an elastic beam bonded to rigid surface. Two other important properties are the shear stress and peel strength. Shear stress is the force per unit area in a direction parallel to the wound bed that causes the dressing to slide or buckle. Any disruption of the fragile wound surface breaks the newly formed blood vessels and retarding healing. Peel strength can similarly be defined as the force per unit area needed to remove the dressing when applied in a direction 90° to the wound’s surface.

Figure 4.3.3.1 Two possible forces on a dressing: (A) shear stress (B) peel force

In this chapter, I would like to study about alginate and chitosan based wound dressings that I most interested as I survey the literature about wound dressing for this term paper.

Chitin, a naturally abundant mucopolysaccharide, and the supporting material of crustaceans, insects, etc., is well known to consist of acetamido-2-deoxy-b-D-glucose through α β (1→ 4) linkage. Chitin can be degraded by alchitinase. Its immunogenicity is exceptionally low, in spite of the presence of nitrogen. It is a highly insoluble material resembling cellulose its solubility and low chemical reactivity. It functions naturally as a structural polysaccharide. Chitin is a white, hard, inelastic, nitrogenous polysaccharide and the major source of surface pollution in coastal areas. Chitosan is the N-deacetylated derivative of chitin, although this N-deacetylation is almost never complete. A sharp nomenclature with respect to the degree of N-deacetylation has not been defined between chitin and chitosan. Chitin and chitosan are recommended as suitable functional materials, because these natural polymers have excellent properties such as biocompatibility, biodegradability, non-toxicity, adsorption properties, etc. lose in its properties. Chitin is highly hydrophobic and is insoluble in water and most organic solvents. It is soluble in hexafluoroisopropanol, hexafluoroacetone, chloroalcohols counin conjugation with aqueous solutions of mineral acids and dimethylacetamide containing 5% lithium chloride. Chitosan, is soluble in dilute acids such as acetic acid, formic acid, etc. The hydrolysis of chitin with concentrated acids under drastic conditions produces relatively pure D-glucosamine.

Alginates are anionic block copolymers of α(1-4)-L-guluronic and β(1-4)-D-mannuronic acid and are usually presented as the sodium salt, while chitosan is a cationic copolymer of β (1-4)-2-acetamido-2-deoxy-β-D-glucopyranose and 2-amino-2-deoxy-β-glucopyranose, obtained via deacetylation of the naturally occurring chitin.

Alginate dressings are currently used in the management of epidermel and dermal wounds, and provide a moist environment that leads to rapid granulation and reepithelialization. However, a cytotoxic effect on proliferation of fibroblasts and residual material with inflammation in healing wounds have been reported. Kaltostat and Sorbsan are, both well-established, widely used commercial calcium alginate dressing, have been investigated by Suzuki and co-workers. They have been developed a new alginate dressing (AGA-100) and used Kaltostat and Sorbsan as contol for this purpose. This new dressing is a is a freeze-dried gel cross-linked with ionic bonds. They have reported that:

ü Kaltostat and Sorbsan showed severe cytotoxicity, and, on contrary, that AGA-100 showed no toxicity.

ü The rate of full-thickness wound closure was significantly higher in AGA-100-treated wounds than in Kaltostat- or Sorbsan-treated wounds.

ü Kaltostat and Sorbsan cause a marked foreign-body reaction with dressing debris after closure of full-thickness wounds, due to their solubility, gel hardness and fibrous property. AGA-100, a nonfibrous and covalently cross-linked dressing, was not solubilized in vitro, but biodegradable because of its high water-swelling ratio and the softness of the gel after absorption of wound fluid.

Walker and co-workers have compared another three alginate dressings (A, B, and C) with a carboxymethylated cellulose wound dressing. They developed scanning electron microscopy technique to demonstrate fluid controlling properties of dressings. They have reported that:

ü Alginate wound dressings did not produce a continuously smooth, single gel-like surface, but instead gave the appearance of a patchwork of slightly gelled areas with fibres passing in and out of the gel matrix regions (Fig. 5.1a). The observation would suggest that the alginate fibres were not fully hydrated. An explanation for this could be that irrespective of alginate type, their rate of gel formation is controlled by the ionic exchanges between sodium and calcium ions. A possible consequence of these ion-exchange mechanisms on the outer surface of the alginate fibres would be the production of a weak gel, having poor cohesive properties.

Figure 5.1 Gel formation after of a suspension of P. aeruginosa to fibres from an alginate wound dressing (Alginate A) Bar 10 μm

Figure 5.2 P. aeruginosa suspensions forming a gel-like structure on fibres from alginate dressings (a) Alginate B, (b) Alginate C. Bar 10 μm

ü Bacteria were observed to be drawn up between individual fibres, possibly by a form of capillary action, and some bacteria appeared to be immobilised in the weak gel that was formed (Figs. 5.1b and 5.2).

Figure 5.3 S. Aureus suspensions on fibres from alginate wound dressings (a) Alginate B, (b) Alginate C. Bar 10 μm

ü Not all bacteria were immobilised within the gel, as many bacteria were found to be located on or within grooves of fibres peripheral to the gel region (Fig. 5.3). The alginate wound dressings showed minimal bacterial immobilisation within the weak gels that were formed. Some bacterial populations were visible adhering to the surrounding, presumably nonhydrated, fibres.

Both study emphasize the drawbacks of alginate dressings. Therefore, alginate dressings need to be developed in many aspects. A recent study by Craig and co-workers is about a possible composite dressing which is made from alginate and chitosan sponge. Before examine this study, I would like to examine a study about chitosan based wound dressing.

In this study, a sponge-like asymmetric membrane is developed by Shyu and co-workers as a wound dressing. This asymmetric chitosan membrane wound dressing consists of skin surface on top-layer supported by a macroporous sponge-like sublayer. The top layer which contains skin surface and interconnected micropores is designed to prevent bacterial penetration and dehydration of the wound surface but allows the drainage of wound exudate. The sponge-like sublayer is designed to achieve high adsorption capacity for fluids, drainage of the woundby capillary and enhancement of tissue regeneration.

ü The tissue-compatible asymmetric membranes do not posess antigenicity and toxicity, but impermable to exogeneous microorganisms.

ü The asymmetric chitosan membrane showed excellent oxygen permeability, controlled evaporative water loss and promoted fluid drainage ability but could inhibit exogeneous microorganisms invasion due to its dense top layer and inherent antimicrobial property of chitosan.

ü The evaluation of the results from wound healing studies in rats suggested that the prepared chitosan wound dressing could be a good material to be employed as wound dressing.

Craig and co-workers developed sponges composed of sodium alginate and chitosan via a freeze drying process in order to assess the utility of mixed sponges as potential wound dressings or matrices for tissue engineering. Researchers have examined a range of alginate/chitosan sponges prepared via a lyophilization protocol, specifically in terms of the mechanical, structural and drug release properties in relation to composition. Secondly, they describe the use of texture analysis as a novel means of assessing the mechanical properties of the sponges. Sponges based on polysaccharides such as alginate and chitosan have been studied due to the low toxicity, favourable mechanical properties and capacity for bioresorption of the constituent materials.

Chitosan (150 kDa) and sodium alginate (48 k-186 kDa) were obtained from Sigma-Aldrich Chemie GmbH (Steinheim, Germany). Stock solutions of both 1% w/v chitosan and 1% w/v sodium alginate were prepared in 1% w/v acetic acid and mixed systems containing varying weight ratios of alginate to chitosan (single polysaccharide, 3:1, 1:1 and 1:3) were prepared by mixing the two stock solutions as appropriate, all systems containing a total polysaccharide content of 1% w/v and all formed clear solutions at room temperature. For the dissolution studies, paracetamol (Sigma) was added to each solution to give a drug concentration of 0.1% w/v. The solution was then poured into four plastic weighing boats (~25 ml each) with dimensions 60×60×8 mm, frozen overnight at -18 °C and freeze dried overnight in an Edwards freeze dryer. Foaming agents were not used in this study to prevent any possible effect they may incur on the morphological structure or mechanical strength of the sponges.

Initial inspection of the sponges indicated that all had flexible textures with considerable bending possible prior to fracture. Given the necessity of a combination of mechanical robustness and flexibility that will inevitably be required for in vivo applications, these initial indications were considered to be promising.

Fig. 5.4a shows the maximum force (‘hardness’) for the sponges under compression as a function of composition. The chitosan sponge was clearly considerably more resistant to compression than the alginate or mixed systems (P <0.05). Similarly the alginate alone gave the weakest sponge, while the mixed systems showed intermediate ‘hardness’ values.

The tensile force profile of the sponges (Fig. 5.4b) showed a different rank order with respect to sponge composition in that the chitosan and alginate alone showed greater breaking strengths than the mixed systems (P <0.05). The elongation values (Fig. 5.4b) were similar in all cases (no statistically significant differences), with only very limited extension taking place prior to breakage. The lack of correlation between the hardness and tensile force is of interest as it indicates that while the chitosan sponges show favourable rigidity (hardness) and resistance to breakage (tensile force), the alginate sponges appear to be more pliable while still having a relatively high strength.

Figure 5.4 (a) the compression force on first and second compression (b) the tensile force and elongation for mixed and single component alginate and chitosan spoges (3:1, 1:1 and 1:3 alginate:chitosan)

Figure 5.5 SEM images for sponges containing (a) alginate alone (b) chitosan alone and (c) 3:1 alginate:chitosan

As shown in Fig. 5.5a and b, there were clear differences in the appearance of the fibrillar structure of the sponges depending on the composition. The pure alginate and chitosan showed a reasonably regular network, for the chitosan and alginate alone, with approximate pore sizes of approximately 20 and 10 mm, respectively. The mixed systems, however, showed a much more irregular morphology, as indicated in Fig. 5.5c. This may at least partially explain the relatively low values for the tensile force seen for the mixed sponges, as the less well defined and regular mesh network may be less resistant to rupture, probably due to the presence of weak areas caused by particularly thin fibrillar architecture which may allow propagation of a tear through the system.

The dissolution profiles of the paracetamol from the sponges (Fig. 5.6) indicated that slow release was apparent for the mixed systems and the chitosan, using the paracetamol tablet as a comparator. Only the pure chitosan and alginate sponges showed complete drug release after 24 h.

Clearly, therefore, it is possible to manipulate both the mechanical and drug release properties of the sponges altering the polysaccharide composition.

In this term-paper, functions and properties of skin, principles of wound healing, types and properties of wound dressings and their applications are reviewed. There are a number of materials that are commercially available as wound dressings. A variety of natural and synthetic polymers have been used as wound dressings. Synthetic polymers are generally used to create a barrier to bacteria and prevent heat and fluid loss from wound. Biological polymers can be used as biodegradable wound dressinfs and are imcorporated into wound tissue. They also promote wound healing and act as substrates for epidermal cells and fibroblasts grown in cell culture.

Some recent studies are focused on biological polymers due to biocompability. Alginates and chitosan are two of the popular biological polymers used as wound dressings. However, major drawbacks about alginate wound dressings have been reported. On the other hand, the use of alginate and chitosan, which is a good material for wound healing, together seems to be a good formula to manipulate both the mechanical properties and the drug release properties of the dressing. I suggested to investigate the most proper composition of alginate – chitosan sponges to supply optimum healing conditions for wounds.

Bactigras consists of a cotton leno-weave fabric, impregnated with Soft Paraffin BP, containing 0.5% w/w Chlorhexidine Acetate BP.

Chlorhexidine is an antimicrobial agent that is active against a wide range of Gram-positive and Gram-negative bacteria but inactive against spores, fungi and viruses; it is more effective against Gram-positive than Gram-negative organisms, and some species of Pseudomonas and Proteus are of limited sensitivity.

Bactigras is used as a wound dressing for the prevention of infection in minor skin loss injuries and ulcerative wounds. It is not the product of choice for the treatment of existing wound infections as the amount of chlorhexidine that is released from the dressing is limited, but Bactigras may be used as an adjunct to systemic antibiotic therapy where appropriate.

Bactigras is contra-indicated in patients who are known to be hypersensitive to chlorhexidine.

Prior to the application of the dressing, the wound should be cleansed with a sterile solution of normal saline. A single layer of Bactigras is then applied and covered with an absorbent pad, held in place with tape or a bandage, as appropriate.

The frequency of dressing changes will depend entirely upon the nature of the wound, but wounds considered at risk of infection should be dressed daily.

Bactigras is presented individually wrapped in peel pouches, sterilised by gamma radiation.

In this nanocrystalline form, metallic silver exhibits pronounced antibacterial activity against a wide range of Gram-positive and Gram-negative bacteria including strains resistant to many types of antibiotics. It is also effective against clinically important strains of yeasts and fungi.

Acticoat is used as an antimicrobial barrier layer for partial and full-thickness wounds such as burns, donor sites and graft recipient sites that are judged to be at risk from infection.

Acticoat is contraindicated in patients with known hypersensitivity to any of the components of the product. If signs of a sensitivity reaction develop during use, treatment should be discontinued. No safety issues associated with the use of Acticoat have been identified to date.

It is recommended that prior to use Acticoat be moistened with sterile water, not saline. This will help to ensure that the dressing provides a moist wound-healing environment whilst enabling the silver to exert its antimicrobial effect.

If necessary, the dressing may be trimmed to the appropriate size and shape of the wound prior to application taking care that the darker blue surface is placed in direct contact with the skin.

Acticoat should be covered with a secondary dressing the choice of which is determined by the degree of exudate produced by the wound and held in place with surgical tape or a bandage as appropriate.

It is recommended that the dressing be left in place for a maximum of three days, although on very heavily exuding wounds, it may be necessary to replace it more frequently.

Acticoat should not be used with oil-based products or other topical antimicrobials.

If applied to very lightly exuding wounds there is a possibility that the dressing may dry out and adhere to the wound surface. This is more likely to happen if the secondary dressing is very absorbent or highly permeable to water vapour.

If adherence becomes a problem the dressing should be soaked off to avoid causing pain or trauma to the underlying tissue.

Acticoat is presented in laminated peel pouch, sealed with a laminated cover and sterilised by gamma irradiation.

Mepilex is an absorbent, low-adherent dressing made from polyurethane foam. The outer surface of the foam is bonded to a vapour-permeable polyurethane membrane, which acts as a barrier to liquid and microorganisms. The membrane, which has a wrinkled appearance, is applied in this way to accommodate the slight swelling that occurs as the dressing absorbs exudate. The wound contact surface of Mepilex is coated with a layer of soft silicone that does not stick to the surface of a wound or cause trauma to delicate new tissue upon removal.

This soft silicone layer is also slightly tacky, which facilitates application and retention of the dressing to intact skin, but does not cause epidermal stripping or pain on removal. This gentle adhesion also tends to prevent maceration by inhibiting the lateral movement of exudate from the wound on to the surrounding skin.

Mepilex is suitable for dressing many types of exuding wounds including leg and pressure ulcers, and traumatic wounds resulting in skin loss. It may also be used under compression bandaging. The dressing absorbs exudate and maintains a moist wound-healing environment whilst minimising the risk of maceration.

The manufacturers have identified no absolute contra-indications to the use of Mepilex

The wound contact surface of the dressing is protected by a divided plastic film that must be removed before use. If clinically indicated, the wound should be cleaned and the surrounding skin thoroughly dried. A dressing should be selected that overlaps the wound margin by at least two centimetres. If required Mepilex may be cut to size or shape before removal of the protective film. Once in position the dressing may be held in place with a bandage or other suitable retention aid. Additional absorbent pads are not usually required, as the plastic membrane on the outer surface of the dressing will prevent the passage of exudate from the Mepilex to the secondary absorbent layer.

The interval between changes will normally be determined by the degree of exudate produced but the dressing may be left undisturbed for several days on clean lightly exuding wounds.

The presence of clinical infection does not preclude the use of Mepilex provided that appropriate antimicrobial therapy is also provided. Sloughy wounds dressed with Mepilex may initially appear to increase in size due to autolytic debridement promoted by the moist conditions produced beneath the dressing. This is normal and to be expected Mepilex should be stored in dry conditions below 35 °C (95 °F).

Mepilex is supplied individually wrapped in paper/plastic laminated peel pouches, sterilised by ethylene oxide.

The silver on the polyethylene mesh is applied by a vapour deposition process, which results in the formation of microscopic, `nanocrystals' of metallic silver.

Acticoat 7 is marketed as an antimicrobial barrier layer for partial and full-thickness wounds such as leg ulcers, pressures sores and other chronic wounds, which are judged to be critically colonised with bacteria or at risk from infection.

Acticoat 7 is contraindicated in patients with known hypersensitivity to any of the components of the product. If signs of a sensitivity reaction develop during use, treatment should be discontinued. No safety issues associated with the use of Acticoat 7 have been identified to date.

It is recommended that prior to use Acticoat 7 be moistened with sterile water, not saline. This will help to ensure that the dressing provides a moist wound-healing environment whilst enabling the silver to exert its antimicrobial effect. If necessary, the dressing may be trimmed to the appropriate size and shape of the wound prior to application taking care that the darker blue surface is placed in direct contact with the skin. The Acticoat 7 should then be covered with a secondary dressing that is appropriate for the degree of exudate that is produced by the wound and the whole dressing held in place with surgical tape or a bandage as appropriate.

Acticoat 7 may be left in place for a maximum of seven days although in very heavily exuding wounds it may be necessary to replace it more frequently.

Acticoat 7 should not be used with oil-based products or other topical antimicrobials.

If applied to very lightly exuding wounds, there is a possibility that the dressing may dry out and adhere to the wound surface. This is more likely to happen if the secondary dressing is very absorbent or highly permeable to water vapour.

If adherence becomes a problem the dressing should be soaked off to avoid causing pain or trauma to the underlying tissue.

Acticoat 7 is presented in laminated peel pouch, sealed with a laminated cover and sterilised by gamma irradiation.

Mepilex Border is suitable for dressing many types of exuding wounds including leg and pressure ulcers and traumatic wounds resulting in skin loss. It may also be used under compression bandaging. The dressing absorbs exudate and maintains a moist wound-healing environment whilst minimising the risk of maceration.

The manufacturers have identified no absolute contra-indications to the use of Mepilex Border

The wound contact surface of the dressing is protected with a divided plastic film, which must be removed before use. If clinically indicated, the wound should be cleaned and the surrounding skin thoroughly dried before application of the dressings. If additional fixation is required this should only be applied around the margins of the dressing.

The interval between changes will normally be determined by the amount of exudate produced by the wound, but the dressing may be left in place for several days on clean non-infected wounds.

The presence of clinical infection does not preclude the use of Mepilex provided that appropriate antimicrobial therapy is also provided.

Sloughy wounds dressed with Mepilex Border may initially appear to increase in size due to autolytic debridement promoted by the moist conditions produced beneath the dressing. This is normal and to be expected.

Mepilex Border is supplied individually wrapped in paper/plastic laminated peel pouches, sterilised by ethylene oxide.

Promogran consists of a sterile, freeze dried matrix composed of collagen and oxidised regenerated cellulose (ORC), formed into a sheet approximately 3 mm thick cut into hexagonal pieces.

In the presence of wound exudate the matrix absorbs liquid and forms a soft, conformable, biodegradable gel that physically binds and inactivates matrix metalloproteases (MMPs), which have a detrimental effect on wound healing when present in excessive quantities^[1].

The gel also binds naturally occurring growth factors within the wound and protects them from degradation by the proteases, releasing them back into the wound in an active form as the matrix is slowly broken down.

Promogran is indicated for the management of all types of chronic wounds that are free of necrotic tissue and visible signs of infection. These include leg ulcers, both venous and arterial in origin, pressure sores and ulcers that occur on the feet of patients with diabetes. The matrix, which also has haemostatic properties, can be used in conjunction with compression therapy.

Promogran is contraindicated in patients with known hypersensitivity to either of the components of the product i.e. ORC and collagen. If signs of a sensitivity reaction develop during use, treatment should be discontinued.

No safety issues associated with the use of Promogran in the treatment of pressure ulcers, venous ulcers and diabetic ulcers have been identified to date.

Before treatment, dry necrotic tissue must first be removed using an appropriate technique.

The matrix should be applied directly to the wound using sufficient pieces to completely cover the wound bed.

In the treatment of very dry wounds, sterile saline or Ringer's solution should be used to hydrate each sheet prior to application to initiate the gelling process.

Once in place the Promogran matrix must be covered with a low-adherent secondary dressing that will conserve moisture and maintain a moist wound-healing environment.

The gel that is formed by interaction with wound exudate is biodegradable and need not be removed at each dressing change unless it is necessary to cleanse the wound for some other reason.

The interval between dressing changes is determined principally by the condition of the wound. In heavily exuding wounds, it may be necessary to replace the matrix daily initially, but on lightly exuding wounds it may be left undisturbed for 2-3 days.

If infection develops during treatment, appropriate antimicrobial therapy should be initiated.

No data has been generated to date on the use of this product with topical medicaments.

Promogran is presented in a transparent waterproof peel pouch, sealed with a laminated cover and sterilised by gamma irradiation.

Mepitel is a porous, semi-transparent, low-adherent wound contact layer, consisting of a flexible polyamide net coated with soft silicone. The silicone coating is slightly tacky, which facilitates the application and retention of the dressing to the peri-wound area. This gentle adhesion also tends to prevent maceration by inhibiting the lateral movement of exudate from the wound on to the surrounding skin.

The nature of the bond that forms between Mepitel and the skin surface is such that the dressing can be removed with minimum pain and without damaging delicate new tissue.

Mepitel is not absorbent, but contains apertures or pores approximately 1mm in diameter that allow the passage of exudate into a secondary absorbent dressing.

Mepitel is used in the management of wounds where adherence of a dressing to the underlying tissue represents a particular clinical problem. Typical applications include skin tears or abrasions, surgical excisions, second-degree burns, blistering conditions such as epidermolysis bullosa, lacerations, partial and full thickness grafts, and skin damage following radiotherapy or steroid therapy.

The manufacturers have identified no absolute contra-indications to the use of Mepitel

The dressing is supplied between two layers of plastic film, which must be removed before use. Prior to application, if clinically indicated, the wound should be cleansed and the surrounding skin thoroughly dried. A dressing should be selected that overlaps the wound margin by at least two centimetres and, if necessary, this may be cut to size or shape before removal of the protective films. If more than one piece of Mepitel is required, the dressings may be partially overlapped, ensuring that the pores are not blocked. Moistening gloves with sterile water or saline will help to stop the dressing sticking to the fingers and thus facilitate application. Once in position the dressing should be smoothed into place, ensuring a good seal with the surrounding skin, and covered with an appropriate absorbent secondary dressing and a suitable fixation device or bandage.

In contoured or jointed areas (e.g. under arm, under breast, inner elbow, groin, deep wounds), it is important to ensure that sufficient padding is applied to keep the Mepitel in intimate contact with the wound surface.

Where clinically indicated, topical steroids or antimicrobial agents can be applied either over or under Mepitel.

Depending on the nature and condition of the wound, Mepitel may be left in place for extended periods, up to 7-10 days in some instances, but the outer absorbent layer should be changed as frequently as required. When Mepitel is used for the fixation of skin grafts and protection of blisters, it is recommended that the dressing should not be changed before the fifth day post-application.

As with all types of dressings, wounds should be regularly monitored for signs of infection or deterioration. When used on bleeding wounds, or wounds producing high viscosity exudate, Mepitel should be covered with a moist absorbent dressing pad. If Mepitel is used on burns treated with meshed grafts, or applied after facial resurfacing, imprints can occur if excess pressure is placed upon the dressing. Following facial resurfacing the dressing it is recommended that the dressing be lifted and repositioned at least every second day.

Mepitel is supplied individually wrapped in paper peel pouches, sterilised by ethylene oxide.

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3. Feldman, D., Barker, T., Blum B., Bowman, J., Kilpadi, D., Redden, R., “Biomaterial-enhanced regeneration for skin wounds”, in Biomaterials and Bioengineering Handbook ed. Wise, D.L, Marcel Dekker Inc., 2000, US, p 807-841

4. Fitzpatrick, T. B., Eisen, A. Z., Wolft, K., Freedberg, I. M., “Dermatology in General Medicine V2”, 4^th ed., McGraw Hill Inc.,1993, US, p 2839-2840

5. Hasirci, N., Kutay, S., Tincer, T., “Polyurethanes as biomedical materials”, British Polymer Journal, 23, 1990, 267-272

6. Kane, J. B., Tompkins, R. G.,Yarmush, M. L., Burke, J. F., “Burn dressings”, in Biomaterials Science – An Introduction to Materials in Medicine, ed. Ratner, B. D., Hoffman, A. S., Schoen, F. J., Lemans, J. E., Academic Press, 1996, US, p 360-370

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9. Shyu, S. S., Mi, F. L., Wu, Y. B., Lee, S. T., Shyong, J. Y., Huang, R. N., “Fabrication and charaterization of a sponge-like asymmetric chitosan membrane as a wound dressing”, Biomaterials, 22, 2001, 165-173

10. Silver, F. H., “Biomaterials, Medical Devices and Tissue Engineering – An Integrated Approach”, Chapman and Hall, UK, 1994, p 46-91

11. Silver, F. H., Doillon, C., “Biocompatibility – Interactions of Biological and Implantable Materials V1: Polymers”, VCH Publishers, US, 1989, p 199-218

12. Suzuki, Y., Tanihara, M., Nishimura, Y., Suzuki, K., Yamawaki Y., Kudo, H., Kakimaru, Y., Shimuzu, Y., “In vivo evaluation of a novel alginate dressing”, Journal of Biomedical Materials Research, 48(4), 1999, 522-527

13. Walker, M., Hobot, J. A., Newman G. R., Bowler P. G., “Scanning electron microscopic examination of bacterial immobilisation in a carboxymethyl cellulose (AQUACEL^®) and alginate dressings”, Biomaterials, 24, 2003, 883-890