Modern wound dressings: a systematic approach to wound healing.

Journal of Biomaterials Applications http://jba.sagepub.com/

Modern Wound Dressings: A Systematic Approach to Wound Healing Michael Szycher and Steven James Lee J Biomater Appl 1992 7: 142 DOI: 10.1177/088532829200700204 The online version of this article can be found at: http://jba.sagepub.com/content/7/2/142

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Modern Wound Dressings: A Systematic Approach to Wound Healing MICHAEL SZYCHER, PH.D. AND STEVEN JAMES LEE, M.B.A., J.D.

PolyMedica Industries, Inc. 2 Constitution Way Woburn, MA 01801

ABSTRACT: The advent of modern wound care management constitutes one of the most innovative applications of medical device technology. The foundation for wound care recent advances has been built upon the developments achieved in polymer technology over the last three decades. New and unique materials have been engineered to provide properties with significant technical and clinical benefits. These new wound care products were made possible by the convergence of three interrelated disciplines: (1) more complete understanding of the underlying principles of dermal wound healing processes, (2) new elastomeric polymers capable of being fabricated into protective dressings, and (3) advances in breathable adhesive technology. The following discussion provides a critical review of the current status of technology and the worldwide opportunities for improved wound management products. Particular attention is focused on the clinical applications of the newer, breathable dressing products, which approximate a temporary synthetic artificial skin.

INTRODUCTION

American population becoming demographically hesegment of the population aged growing is

older. The 65 years and older is rapidly in the U.S. as well as the rest of the world, and it is this segment of the population that has historically produced the highest demand for health care. In part, this aging population is the result of increased life expectancies brought about by improved health care. 142


143 Based upon data from the Population Reference Bureau, in 1989 approximately 31 million people in the United States, or about 12.4% of the population, was aged 65 years or older. By 2020, with the aging of the &dquo;Baby Boom&dquo; generation, this segment is expected to grow to about 52 million people, and account for 17.7% of the population (see Exhibit 1). In some foreign countries, this trend is expected to be even more pronounced. For example, in Japan, the population segment aged 65 or older is expected to double from 12% of the population to 24% by 2020. The elderly have historically had medical expenditures in a disproportionately higher amount relative to their percentage of the population. According to the U.S. Bureau of the Census and the American Hospital Association, persons 65 or older (who comprise 12% of the population) account for 35% of the hospital admissions, 46% of the hospital in-patient days, and 39% of health care expenditures. With the onset of an aging population will come a proliferation of diseases that are prone to attack the geriatric population segment. Many of these geriatric patients will be institutionalized or bedridden, where they become susceptible to decubitus and venous stasis ulcers.

Exhibit 1. The age of the world’s population is steadily increasing. By the year 2020, nearly twenty percent of the population will be approaching 65 years in the U.S. and Canada. Downloaded from jba.sagepub.com at SIMON FRASER LIBRARY on November 8, 2014

144 At the present time, decubiti and venous stasis ulcers constitute two of the largest categories of chronic dermal wounds. Dermal wounds are structural or physiological disruptions of the integument that incite normal or abnormal repair responses. About 2 million Americans are treated for decubiti [1] and 500,000 for venous ulcers yearly [2]. Many of these patients are drawn from a population of almost 11 million patients who are diabetic and prone to develop chronic, slow-healing diabetic nephropathy ulcers on their legs and feet. Chronic dermal wounds heal very slowly and often linger on the patient for weeks, months, or even years. Patients afflicted by these wounds commonly experience secondary complications, including infections, metabolic and nutritional disorders, and other factors that make wound management more challenging. A dermal wound is considered healed [3] when the maturation process has reestablished continuity of skin surface and when tissue integrity is sufficient for normal activity. While the phases of healing are identical for all patients, the rate of healing depends on the status of the individual. Older, malnourished patients, or patients with systemic diseases (e.g., diabetes) heal more slowly than young, well-nourished patients. Burns represent another category of common dermal wounds. Approximately 2 million Americans are treated annually for burns; of these patients about 80,000 are hospitalized for third-degree burns. Burns occur in 10 seconds when the heat source is 75 degrees Celsius, or burns occur in only 0.1 second following exposure to a heat source at 130 degrees Celsius, as shown in Exhibit 2. Another large category of dermal wounds result from more than 24 million (in 1991) surgical operations performed in public or private hospitals. At present, surgical incisions are closed with staples or traditional sutures. Newer wound dressings are being evaluated as wound closures, which are destined to displace external sutures in many ap’

plications. Wound care categories of treatment, like all aspects of medical care, have been affected by the development of DRGs (Diagnostic Related Groups), which aim to reduce the national cost of patient care. The current cost of a hospital stay for treatment of dermal ulcers ranges from about $2,500 to $30,000 per patient [4], but may be reduced through the use of advanced dressings that can remain on the wound site longer before needing to be changed. In addition, the DRGs encourage a shift from hospital care to home care, whenever possible. ’Ib meet these demands, physicians and manufacturers alike are introducing new modalities in wound dressings that are &dquo;patient friendly,&dquo; may be applied or removed by the patient, and as a result reduce the overall cost of Downloaded from jba.sagepub.com at SIMON FRASER LIBRARY on November 8, 2014

145

Exhibit 2. The time to burn (severity) is

geometrically proportional to heat source tem-

perature.

treatment. ’Ib effect

changes in treatment modalities, modern wound primarily on enhancing the healing microendressings vironment for optimal management of these chronic dermal wounds. are

focused

HISTORICAL PERSPECTIVE

It is apparent that man has been dressing dermal wounds since prehistoric times. The first dressings used may well have been tree leaves or mud packs. As experience accumulated, many other naturally-occurring substances were tried with varying degrees of success. In parts of Africa and South America, the art of dressing a wound still constitutes the major portion of the medical knowledge of local health pro-

viders. The oldest written

descriptions of wound dressings are found in the Smith (ca. 1700 B.C.) and the Papyrus Ebers (ca. 1500 B.C.), in which oiled frog skins and other greased bandages were advised as wound coverings [5]. Skin grafting was reported in the ancient Hindu Papyrus


146 document Susruta Sanhita (700 B.C.) for the repair of nose and ear defects [6]. Unfortunately most of these remedies had unacceptably high instances of infection. It has only been since the beginning of the twentieth century that knowledge of wound healing progressed to the point where medical professionals have been capable of successfully intervening in the natural healing process. Beginning in the late 19th century, when Pasteur’s germ theory

gained acceptance, wound care was based on two principles: cover the wound and keep it dry. This simplistic concept was rigorously applied into the 20th century. Wound dressings promoting a dry (and presumably &dquo;germ-free&dquo;) wound environment became the mainstay of wound care. These dressings, made from cloth, cotton, and gauze were passive in nature and were incapable of enhancing the natural healing process. Cloth, cotton, and gauze excel at absorbing wound exudate and physically removing surface necrotic tissue. When kept moist by continual irrigation, their healing effects may equal other dressings; howthey are difhcult to keep continually moist [7]. In addition, none of these dressings provide a bacterial barrier; when removed, they dry saline ever,

and adhere to the wound, which may remove viable tissue from the wound surface, resulting in delayed wound healing [8]. During World War I, the French physician, Lumiere, introduced a successful artificial wound dressing consisting of cotton gauze impregnated with paraffin (tulle gras). The technology of wound care failed to improve beyond tulle gras until 1941. At that time, in the Oxford War Manuals, Wallace advocated the use of one percent gentian violet solution (a mild antimicrobial), followed by scab formation by force drying the blood with a warm air current from an electric drier [9]. The next advance came in 1942, when the first semisynthetic polymer, methylcellulose, was applied by Pickrell [10] as a wound dressing. In this preparation, methylcellulose served as an inactive vehicle for the delivery of sulfonamide antimicrobial to cover burns, which was the beginning of the use of synthetic materials for the enhancement of the natural

biologic processes in wound healing. Three laboratory studies launched a revolutionary approach to wound healing that fostered the concept of moist wound healing as an improvement over dry dressings. The concept embodied in these studies is that moist wound healing promotes direct interaction with the wound environment, as opposed to passive protection. In 1958, Odland observed that a blister healed faster when kept intact [11]. Four years later, in 1962, Winter demonstrated in pigs that the epithelialization rate of wounds covered with polyethylene films was double that of wounds healed under a dry scab [12]. Hinman and Maibach later reproDownloaded from jba.sagepub.com at SIMON FRASER LIBRARY on November 8, 2014

147

duced these findings in human volunteers, thereby firmly establishing the beneficial effect of moist wound healing in humans [13]. Early in the 1970s, Rovee showed that a moist, crust-free environment enhanced the migration of epithelial cells across the wound and facilitated

reepithelialization [14]. The key step in wound healing is the migration of epithelial cells across the surface of the wound. Epithelial cells require a critical level of moisture at the wound site to facilitate optimal migration. Winter and coworkers showed that epithelialization occurs about 40% faster in a moist environment than in a dry environment [15]. Winter’s explanation for this observation is that in open, desiccated wounds, epithelial cell migration is inhibited by collagen bundles that form in scabbed wounds. Moreover, since the wound fluid has been shown to possess multiple growth factors that stimulate angiogenesis and epithelialization, it follows that dry wounds, deprived of this fluid, heal more slowly with less effective repair of skin and blood vessels [16,17]. The synthetic materials used in the manufacture of wound dressings have undergone explosive growth in the past 20 years. Up until the mid-1970s, most of the commercial dressings consisted of woven cotton gauze

or non-woven

blends of rayon with other fibers

(e.g., polyester

or

cotton). These &dquo;traditional&dquo; dressings function to absorb exudate, cush-

wound, allow for a dry site, hide the wound from view, and atprovide a barrier to contamination. Most clinicians removed these dressings very early in the healing process in order to expedite further drying of the wound site. It was believed that a dry environment was hostile to bacterial proliferation. Unfortunately, a dry wound ion the

tempt

to

site was also an impediment to the viability of mammalian cells and tissues involved in the healing process. The cotton woven, blended-cotton woven, and non-woven dressings with absorbent and cushioning properties continue to fill certain needs in wound treatment where it is important to drain away large quantities of exudate or to protect a site from further mechanical trauma. These first generation materials are also used to pack open wounds in order to eliminate dead-space and establish hemostasis. ’

WOUND HEALING

.

The process of wound healing is a predictable series of temporal events which results in the restoration of the wounded tissue to the normal or quasi-normal state found prior to injury. Some species can regenerate lost limbs, faithfully reproducing the tissue (e.g., certain amphibians and reptiles). In man, however, the ability for regeneration Downloaded from jba.sagepub.com at SIMON FRASER LIBRARY on November 8, 2014

148

has been lost in most tissues. Healing or repair proceeds by cell migration, proliferation, differentiation and scar formation (production of fibrous tissues) to re-establish a functional state. Wound healing is a natural process that occurs after any injury to the skin. The wound may be elective, as in surgery, exogenous as in decubitus ulcers, or traumatic as in accidents. In addition the wound may be deemed acute and/or chronic. Normal wound healing is an orderly, predictable progression of steps used by the body to resolve impaired tissue

integrity. There

are

four documented

phases of the wound healing process:

1. Inflammation 2. Migration 3. Proliferation 4. Maturation

These four

,

phases occur sequentially, with the timing of each phase series of variables, including wound type, infection, dependent local blood supply, underlying patient status, pathology, etc. The first phase, inflammation, typically lasts about 24 hours and involves clotting, vasodilation and phagocytosis. During the second phase, migration, which may last 3-5 days, polymorphonuclear leukocytes and macrophages clear the wound of de. vitalized and unwanted material. Macrophage migration stimulates the formation of fibroblasts which results in the synthesis of collagen, the major structural protein for repair of the body. The third phase, proliferation, involves granulation and de novo collagen synthesis which organizes to produce strands from which skin, tendon, cartilage and bone tissue are fashioned. Migration of epithelial cells and the formation of granulation tissue is also observed during this 3-24 day period. During this phase, closure of the epithelium is normally attained. The fourth and final phase, maturation, takes place over a much longer time frame lasting 24 days-1 year. During this period the repaired tissue increases in vascularity and undergoes a reorientation of the collagen fibers. The new tissue slowly increases in tensile strength (up to 70% of its original strength) and simultaneously assumes the color of the surrounding skin. Throughout the healing sequence the wound will produce a mixture of fluids that is termed exudate. The biochemical and physical composition of exudate is a function of wound type and its phase in the healing sequence. Exudate may range from blood and serous fluids to highly viscous proteinaceous liquids. Exudate is beneficial to the wound reon a


149 process and contains the cellular and enzymatic materials that allow for wound healing. There are two additional bodily processes that occur during the healing sequence: contraction and re-epithelialization. Contraction is the bodily process by which wounds with large area skin loss become smaller without the requirement for secondary area skin closure. Under certain conditions wound contraction produces a result which is at best cosmetically unacceptable and at worst potentially debilitating. Epithelialization is important in wounds where there is significant loss of layers of tissue but not large total loss of skin area. After injury the epithelial cells at the wound edge migrate towards the open areas of the wound. Epithelial cells will only migrate over a living tissue bed and as a result move under the layer of the clot and eschar (scab). Eventually the eschar is pushed off and the migrated epithelial ’cells reestablish skin mass (Figure 1). The healing times and sequence of phases in wound healing can be adversely affected by bacterial contamination. When the degree of contamination attains a threshold level the wound becomes infected and additional measures need to be taken to restore the healing process. Avoiding the complications of infection by avoiding wound contamination, both particulate and microbial, is a major objective of modern clinicians in their use of wound dressings. Armed with a basic understanding of wound healing and the adverse factors that complicate this process we are now in a position to examine particular wound types. The type of wound dictates the parameters, such as exudate production and speed of healing, which should be addressed by new materials used as constituent elements in the new generation of wound dressing products.

pair

.

Figure 1. Regenerating epidermal cells are forced to &dquo;tunnel&dquo; below the eschar to attain wound closure. This tunneling delays wound closure. Downloaded from jba.sagepub.com at SIMON FRASER LIBRARY on November 8, 2014

dry

wound

150

While certain aspects of the healing process could theoretically be speeded up by active intervention, such as administration of growth promoters, most research directed towards developing wound dressings has concentrated on trying to provide an ideal environment for the fastest natural healing to occur. As mentioned above, the need to keep out contamination has long been recognized. However, the desirability of maintaining the delicate balance between absorbing excess exudate and preventing the wound from drying, or precluding maceration is a more recently formulated requirement. Modern wound dressing theory, suggests promoting the dynamic equilibrium between exudate absorption and the maintenance of optimal moisture at the wound surface. In addition, it would promote gaseous exchange to.provide the wound with proper oxygen tension; insulate the wound against temperature extremes; and provide a bacterial barrier. The ultimate wound dressing also would be completely non-adherent to the wound bed to allow the dressing to be changed with minimal trauma to the fragile and newly-formed epithelium. From a patient point of view it would also be desirable to eliminate discomfort normally associated with wound dressings and allow conformation to difficult body contours. This is a tall order for any single medical device, particularly considering the diversity of wound types. Success in achieving these goals has had to await a combination of new materials, better design, and perfection of complex manufacturing techniques. The focus of this critical review shall now turn to major new developments in a new generation of wound care products. WOUND CLASSIFICATIONS

There are numerous methods for the classification of wounds. The method adopted here categorizes wounds into two broad types: wounds without significant tissue loss and wounds with significant tissue loss. Wounds without significant loss of tissue are typically incision wounds formed either as a result of surgery or trauma. Some wounds which result in the loss of significant tissue may be the result of trauma or as a secondary event in chronic ailments such as vascular insufficiency that leads to ulcer formation. There are also iatrogenic wounds (caused by the health care provider) which result in the loss of tissue and are exemplified by skin grafts, donor sites, dermabrasions, etc. Viewed from-the vantage point of designing a wound dressing, acute and chronic wounds with significant loss of tissue are a challenging and desirable area of interest. The remainder of this review will conDownloaded from jba.sagepub.com at SIMON FRASER LIBRARY on November 8, 2014

151 Table 7. Common dermal wounds.

centrate on the current state of the art with respect to wound dressings that address the needs of wounds that involve significant tissue loss. The most common wounds that have significant tissue loss are listed in Table 1.

Dermal Ulcers

categories of dermal ulcers. The first category is dewounds formed when skin is subjected to unrelenting pressure and shear (movement between a bed and skin). These physical There

are

two

cubitus ulcers,

or

factors induce tissue necrosis and ulceration. Only a weightless astronaut is capable of existing in an environment without contact pressure. Unfortunately, earthlings, and especially the elderly and the disabled, have to cope with the effects of pressure every day. &dquo;Pressure&dquo; is a perpendicular load or force exerted on a unit of bodily area. In a sitting position, the deep fascia of the body moves in a downwards direction with respect to the skeleton, while at the same time the skin that is in contact with a bed remains stationary, thus creating &dquo;shear.&dquo; &dquo;Friction&dquo; is the force produced by two surfaces moving across each other. Pressure, shear and friction are implicated in the pathogenesis of decubitus ulcers (also called here &dquo;pressure sores&dquo;) [18]. We can see these principles at work in a patient who is bedridden. The skin is subjected to three stresses: (1) pressure; (2) shear; and (3) friction. This is shown in Figure 2. When a patient is semi-recumbent there is automatically greater pressure, shear and friction placed on the tissues than when the patient is erect. These insults to the body lead to stretching and possible avulsion of local arteries supplying the area [see Figures 3(a), 3(b), and 3(c)]. Friction is often seen clinically when a paralyzed patient or unconscious patient is moved across rough bed linens. By itself, friction causes only abrasions, but it also produces the critical pressure required to produce ulcerations. Shear occurs Downloaded from jba.sagepub.com at SIMON FRASER LIBRARY on November 8, 2014

Diagrammatic representation of decubitus ulcer developmental process. (a) kept healthy by capillary blood supply. (b) In some places of the body, large bony prominences lie close to the skin, especially at the hips, sacrum, heels, elbows, eta (c) When a patient is lying down, the skin is compressed between the bones and the bed. This compresses the skin, and impedes blood supply to that area. At this point there is great risk of developing decubitus ulcers.

Figure

3.

Normal skin is

152


153 Table 2. Decubitus ulcer assessment scale.

when a patient shifts in bed and subcutaneous tissue moves over a bony prominence, resulting in injury to the underlying vasculature. Shear is a significant predisposing factor to ulcer formation and enlarges the area of necrosis. When early signs of a decubitus ulcer, such as reddening or induration of the skin are noted, it is important that action to relieve pressure to the area is taken immediately. Should the sore develop, the wound is objectively assessed by the decubitus ulcer scale shown in Table 2. The prediction of patients at risk (particularly paraplegics or wheelchair bound patients) has been greatly assisted by the development of risk-assessment scores, such as the Pressure Sore Prediction Score (PSPS), utilized in the UK [19]. Table 3 presents the PSPS score in a

summarized fashion. The PSPS is best explained by enumerating the six individual components of the predictive score, as shown below: -

up in bed for &dquo;nd’ answer. Unconscious Mental confusion may

Sitting up

Propped

Table 3. The PSPS pressure

long periods qualify

sore

as a

prediction

means a

&dquo;no&dquo; score.


definite

answer.

154 Poor

general

This may be sudden/severe

illness, such

as

paralysis.

condition

Incontinent Lifts up

Gets up and walks

How often is the patient wet underneath? Can the patient lift himself without help? A &dquo;yes&dquo; answer means that the patient is able to elevate the

pelvis. A &dquo;yes&dquo; answer implies normal, or nearly normal ability to walk. ’

Decubitus ulcers occur when &dquo;there is pressure which is sufficient to lead to an obstruction within the microcirculation of the skin leading to death of the tissue&dquo; [20]. Only three hours of compression in a high risk area can start the process, if the compression pressure is greater than mean capillary pressure. Prolonged pressure greater than mean capillary pressure causes occlusion of blood vessels, depriving tissues of their vital blood supply. Human skin can tolerate pressure as high as 500 mm Hg for short periods. However, if the perfusion pressure of the venous capillary system (approximately 30 to 40 mm Hg) is exceeded for even two hours, tissue damage will occur [21]. Ischemia is the underlying cause of ulceration, and continued pressure results in

greater injury f221. Muscle and subcutaneous tissue is far more susceptible to pressure necrosis than is the skin [23]. In experiments conducted in domestic pigs, whose skin is similar to that of humans, a pressure of 200 mm Hg for 16 hours, or 600 mm Hg for 11 hours, was required for full thickness skin necrosis to occur [24]. In contrast, pressures of only 60-70 mm Hg for 1-2 hours caused muscle fibers to degenerate. Many professionals hold that pressure reduction can be obtained by turning the patient at least every two hours. However, at night this is often impossible, and in some patients (such as the poorly nourished and the very elderly) even two hours in one spot can result in significant pressure damage. It is important to recognize that 90% of all decubitus ulcers occur in only four places, as shown in Figure 4. As expected, 90% of pressure ulcers occur in four places, the sacrum, buttocks, trochanters, etc., as shown in Table 4. The second category of dermal ulcers is ischemic ulcers, which are a direct result of a degeneration of the cardiovascular system. Such degeneration leads to reduced blood flow in.the extremities and subsequent tissue necrosis resulting in the formation of dermal lesions. There are two subcategories of ischemic ulcers called arterial ulcers and venous ulcers. Arterial ulcers are caused by arterial insufficiency and occur when circulation to the lower limbs is compromised, usually ’


155

Figure 4. Decubitus ulcers (pressure sores) develop because of the unrelenting pressure suffered by skin over bony prominences, such as the sacrum, ischeal crest, femoral trochanter, etc.

Such ulcers are common in patients with diabetes mellitus who may suffer from arteriosclerosis and peripheral neuropathy. Arterial ulcers are usually painful, and exquisitely sensitive to touch (except where neuropathy has dulled sensation). They often occur in the lower leg, especially in toes and heels. Venous stasis is another category of ischemic ulcer, caused by unrelieved high pressure in the venous vasculature of the lower extremities and thought to be related to incompetent perforator valves. According to the latest theory, when venous valves do not function properly, the venous capillaries overstretch and become more permeable. Large plasma molecules (i.e., fibrinogen) normally retained in blood escape into the extravascular space. Leaking fibrinogen coagulates around the

by atherosclerosis.


156 Table 4. Common decubitus ulcer locations.

a &dquo;fibrin cuff.&dquo; These cufi’s, in turn, are believed to block oxygen transfer to the skin, and also prevent capillary dilation in response to increased demand for blood supply. These changes lead to tissue death and ulcer formation. Venous stasis ulcers are irregularly shaped, surrounded by edematous tissue and brownish hemosiderin pigmentation. The characteristics of the two types of ischemic ulcers are summarized in Table 5.

capillary, forming

Abrasions

’

Abrasions arise due to trauma, as in the case of &dquo;road rash;’ or from elective procedures such as dermabrasion. These wounds initially produce copious amounts of exudate composed of blood and serous fluid. Traumatic abrasions are frequently contaminated with physical debris and if left unattended may lead to infection.

Table 5. Ischemic ulcers.


157

Donor Sites Donor sites are created by the removal of a thin layer of skin which is utilized as a &dquo;skin graft&dquo; As in the case of abrasions, donor sites exude blood and serous fluid. Donor site wounds are painful and often require the patient to undergo treatment with medications that reduce

pain. Burns Burns are classified in three ways. The first classification is based on the cause of the burn. The second classification is the extent of injury, which is based on depth of tissue damage. Extent of injury is further subclassified as first, second or third degree. The third and final classification is a compilation of the first two classifications to arrive at a severity rating for the affected body surface, as shown in Table 6. Regarding the third classification, or burn severity, the surface area of the body that is burned is frequently assessed using Wallace’s rule of nines, shown diagrammatically in Figure 5. By this theory, the adult body is divided into twelve segments, each represents 9% of the total body surface area. The head and neck, chest, abdomen, upper back, lower back and buttocks, each arm, the front of each leg, and the back of each leg each represent 9% of the body surface area. The genital area represents the remaining 1%. Clinicians total the rule of nines to arithmetically define minor, moderate and critical burns. Minor burns are first-degree burns involving less than 20% of body surface, second degree burns affecting less than 15%, or third degree burns of less than 2% of body surface (ex-

.

&dquo;

Table 6. Burn classification schemes.


158

Figure 5. Wallace’s rule of nines for burn patients.

cluding face, hands, feet, groin and major joints). Moderate burns are first-degree burns of 20 to 75% of total body surface, second-degree burns of 15 to 30%, or third-degree burns of less than 10% of body surface. Critical burns are first-degree burns of more than 75% of body surface, second-degree burns of more than 30% of the body, or third-degree burns of more than 10% of body surface. They also include burns complicated by injuries to the respiratory tract, other soft tissue, or bones. .

_

WOUND 14TANAGEI~TENT

As mentioned earlier, traditional wound treatment theory left the wound exposed to the atmosphere or covered with a textile based Downloaded from jba.sagepub.com at SIMON FRASER LIBRARY on November 8, 2014

159 Table 7. Textile-based wound

dressings.

wound dressing such as gauze (Table 7). Those wounds left open formed an eschar or scab which acted as a biologically-derived wound covering. The eschar is a hard, brittle material composed of dehydrated blood and the proteinaceous components of the wound exudate. The presence of the eschar protects the wound from the external environment. However, during reepithelialization of the wound the advancing cell front from the edges of the wound has to pass under the eschar. This is a long path to avoid an obstacle to epithelial cell migration. When reepithelialization is complete the eschar spontaneously falls from the wound site leaving an indentation which becomes a component of the scar. This process is shown diagrammatically in Figure 6. In contrast to an eschar, the formation of a blister is a natural way to maintain moist conditions, and allow optimal healing. It provides for the optimum microenvironment within which the wound may heal.

Figure 6. Semipermeable wound dressings prevent formation

of eschar

Migrating epithelial cells grate and close the wound unhindered by the presence of a dry eschar. an

optimal

moisture level at the wound bed.


by maintaining are

able to mi-

160 a blister is not a perfect wound covering as its brittle nature makes it prone to damage. Similarly, a blister has little capacity to control excess exudate,

Unfortunately,

’

which from a dressing. The a

practical standpoint is a major requirement in a wound new generation of wound dressings act as a blister with high exudate-handling capacity.

T~xtile-based wound coverings afford a measure of exudate control and are commonly used as primary wound coverings. Although these dressings absorb exudate, they rely on the formation of eschar that intermingles with the textile covering to produce the microenvironment in which tissue repair takes place. A major drawback to textile-based dressings is that on removal, the eschar and textile entanglement leads to damage of the underlying wound bed, therefore increasing the time required to fully heal the wound. Open textile structures also invite invasion by microorganisms. The invasion is further enhanced by exudate &dquo;strike through&dquo; which provides additional pathways along which exogenous bacteria may mi-

grate. Researchers have

long recognized that if a wound dressing could be designed provide the desired moist microenvironment around a wound then a more optimum healing rate will result. If this could be accomplished simultaneously with the ability to control varying levels to

and types of exudate, and prevent the formation of eschar (and the subsequent scarring) then this would be an ideal situation. A great deal of work has been performed in this area over the last 30 years and this has evolved into the theory of moist wound healing.

MOIST WOUND HEALING THEORY In the

early 1960s Winter et al. performed a series of experiments usas a wound model. In this work he monitored, histologically, the rate of re-epithelialization of wounds when covered with a selection of occlusive materials. The results of this work clearly indicated that ing pigs

the rate of epithelialization increased when wounds heal under occlusive or moist coverings.

were

. Since the

allowed to

pioneering work of Winter et al. [25-27] there has been steady acceptance of the fact that a controlled moist wound environment creates a close approximation to ideal wound healing conditions. The traditional belief that absorbent gauze therapy is adequate, with its potential for adhesion and secondary trauma, has given way to the

philosophy that

moist wounds

are

healing wounds.


161

The gradual change from universally applied gauze dressings has been caused in part by a realization that to obtain optimal wound healing conditions the localized wound microenvironment has to be controlled. This thinking has been further extended by understanding that different types of wounds require different types of microenvironments

[28,29].

1 the path of regenerating epithelial cells is blocked when a wound is allowed to form a dry eschar or scab. The epithelial cells must pass below both the eschar and some viable epidermal tissue to cross the moist dermis. The healing process is thus delayed as the cells travel around this obstacle. The burrowing of the epithelial cells under the eschar contributes to the formation of scar-

Referring again to Figure

ring. As depicted in Figure 6, when wound dehydration is prevented by a semi-permeable dressing the migrating epithelial cells at the wound margins can pass through the jellied wound bed and ultimately heal the wound faster. Some practitioners refer to this process as soft-clot healing. It is generally accepted that this results in faster healing. The ideal characteristics of a microenvironmental wound dressing have been detailed by numerous authors. These characteristics are summarized in Table 8 [30,31]. It may be appreciated that historically the maintenance of &dquo;high humidity at the wound interface&dquo; and the &dquo;control of exudate&dquo; were mutually exclusive parameters. The ultimate control of exudate has

,

been construed in the past as its total absorption, as in the case of textile-based dressings. This in turn will render the &dquo;maintenance of high humidity at the wound interface&dquo; a characteristic which is impossible to achieve. Also, &dquo;ease of application and removal;’ when examined more closely, suggests that a dressing should adhere to a wound site without adhesive failure until the patient or clinician wishes to remove it. At the

Table 8. Ideal characteristics of a microenvironmental

dressing.


162 time of removal for changing or when the wound is healed, instant and I painless &dquo;adhesive failure&dquo; is required. The other parameters listed in’hable 8 as &dquo;ideal characteristics&dquo; may only be approached as part of a selection process. In each case one must balance the degree of each characteristic in a new wound dressing so that when it is taken in concert with other characteristics it optimizes wound healing. Compromises and &dquo;trade-offs&dquo; are required to design and produce practical wound dressings. In recent years, there have been many attempts at the development of sophisticated, microenvironmental wound dressings to aid the clinician. This has led to commercially available products which differ in their ability to approach the ideal characteristics of the perfect wound dressing. While these first generation dressings possess a wide spectrum of physical properties, they all have in common a desire to achieve a moist wound healing microenvironment. There has been much published in the scientific journals describing clinical evaluations of such

materials. From the published results of Eaglestein’s research [32] we can generalize the three major advantages of moist environmental wound dressings to be: ~

allowing

more

efficient

~

inducing healing

~

reduction of pain

reepithelialization

of acute wounds

of chronic wounds

Although the first generation wound dressings currently available provide a moist environment, they do so by using markedly different materials, mechanisms of action, and materials of construction. BACTERIAL CONTAMINATION

Some types of bacteria are more pathogenic than others [33]. Microbial adherence to host cells is a prominent feature of bacterial pathogenicity. Pseudomonas aeroginosa and Staphylococcus aureus adhere strongly to host tissue, and are thus highly pathogenic organisms

[34,35]. Moreover, bacteria that colonize or infect skin may be aerobic or anaerobic. As the name implies, aerobic bacteria are capable of growing in the presence of oxygen, while anaeiobic bacteria must grow under hypoxic conditions, since they lack the key enzyme superoxide dismutase. A large majority of the bacteria on normal skin are anaerobes. Anaerobic infections are favored by trauma, reduced blood supply and Downloaded from jba.sagepub.com at SIMON FRASER LIBRARY on November 8, 2014

163 Table 9. Bacteria implicated in dermal infections.

necrotic tissue. This is shown in Table 9 for bacteria that frequently are implicated in dermal infections. Bacterial contamination is a process that is usually restrained by phagocytic action. However, an infection will develop if the four factors listed in 7hble 10 are present. Th reduce the risks posed by microbial contamination, physicians work to ameliorate local conditions (such as A and B in Table 10) that predispose the patient to infection. Proper cleansing and dressing techniques keep wounds free of contaminants, as well as eschar, necrotic tissue and foreign matter. Breathable and absorbent dressings provide a barrier to exogenous infections, and also tend to mobilize infectionfighting components, such as neutrophils and macrophages. FIRST GENERATION 1~IICROENYIRONl~IENTAL WOUND DRESSINGS

First one

generation wound dressings following five categories:

may be classified

as

belonging

of the

1. Thin films 2. Hydrocolloids 3. Hydrogels 4. Foams 5. Alginates

_

Second-generation microenvironmental wound dressings 1. Spyrosorbent dressings 2. Tryptosorbent dressings J

. Table 10. The development of infection.


are:

to

164 Table i ?. Wound

Table 11 lists a selection of the

care

products.

currently available commercial dress-

ings in each of these categories. Since there are many similar products in a particular category of wound dressing, we list only those dressings with

a significant market share. Table 11 also lists two wound dressings considered to be second generation microenvironmental wound dressings: spyrosorbent and tryptosorbent dressings. Table 12 lists major thin film wound dressings available worldwide. The classification of thin film wound dressings consists of synthetic polymeric films which have one surface coated with a pressure sensitive adhesive, such as Op-Site and Tegaderm (see Figure 7). PolyDownloaded from jba.sagepub.com at SIMON FRASER LIBRARY on November 8, 2014

165

Figure 7. Scanning Electron Micrograph (SElB1) of the dressings-Op-Site and ~gaderm.

cross

section of thin film

urethane films are generally agreed to be the material of choice for these types of wound dressings e.g., Tegaderm and Op-Site [36]. The dressings are elastomeric, low profile, and comformable. Thin film wound dressings are indicated for use on -incisions, abrasions, lacerations and in some instances, dermal ulcers. This type of dressing controls exudate by utilizing the polymeric film’s molecular moisture vapor transport properties. When placed on a wound the exudate collects under the dressing (see Figure 8). The aqueous portion of the exudate migrates through the polymeric film to the external environment at a predetermined rate. The rate is dictated by the molecular structure of the film and its thickness. The thinner the film, the higher the moisture vapor transport rate. Associated with the transportation of the aqueous exudate a conTable 12.

Major thin film products.


166

Figure 8. Mechanism of water

vapor transmission in thin films.

centrated proteinaceous material is formed and it remains in contact with the wound surface. In many instances this is considered to be detrimental to wound repair. The currently available thin film wound

.

dressings breathe at a rate which is equivalent to that of intact human skin. When used on moderate to highly exuding wounds, &dquo;pooling&dquo; of exudate is often observed under the dressing. The &dquo;pool&dquo; of exudate has to be aspirated from beneath the dressing thus compromising the bacterial barrier. The &dquo;pooling&dquo; of exudate is an indication that the moisture vapor transport rate is insufficient to cope with the high level of exudate produced by many types of wounds. Thin film dressings have little absorptive capacity (Figure 8). Their mechanism of exudate control is by moisture vapor transmission. The adhesive surfaces often utilize acrylic based pressure sensitive adhesives. These materials adhere aggressively not only to the surrounding intact skin but also to the wound bed. Such adhesion results in injury to the wound at the time the dressing is removed. Although polyurethanes are the materials of choice for the majority of thin film wound dressings, Biobrane~’ is a thin film wound dressing fabricated from silicone rubber [37]. Silicone rubber is well known for its high level of moisture vapor permeability. Biobrane has an enhanced moisture vapor transport rate when compared to other polyurethane thin film dressings (Figure 9). Biobrane is a non-adhesive

dressing. The wound contact surface of Biobrane is coated with a layer of collagen. The collagen coating bonds to the wound bed and facilitates close apposition of the wound dressing. Due to the relative fragility of silicone rubber, a nylon strengthening mesh is embedded in the Biobrane dressing (Figure 10). As in the case of the polyurethane based thin films, Biobrane is not absorptive and utilizes its high moisture vapor transport rate to manage exudate (Figure l1a). It is not, however, sufficiently high to cope with levels of exudate found in many types of wounds such as ’Biobrane is

a

tradename

of Winthrop Laboratories, New York, NY.


167

Figure 9. Moisture uptake as a function of time for a range ings, such as Biobrane, ~gaderm and DuoDerm2 2.

of traditional wound dress-

abrasions and deep lacerations. As a result the Biobrane dressings currently available have been rendered porous by the mechanical punching of holes through the dressing material (Figure llb). The holes are a solution that causes Biobrane to fail one of the optimal characteristics, which is to act as a bacterial barrier at the wound site. Biobrane, as a silicone elastomer-based dressing, is only one example of how manufacturers have modified the molecular structure of polymeric films to alter a wound dressing’s ability to control exudate. Togaderm and Op-Site are examples of other specialized polymeric films

ulcers,

severe

Figure 10. SEM of the DuoDerm is 2

a

tradename of E. R.

cross

section of

a

thin film-Biobrane.

Squibb, New York, NY.


168

Figure lla. Moisture Vapor Transport Rate (MVTH) of Biobrane, compared to Tegaderm and DuoDerm dressings. Biobrane dressing is not absorptive, and utilizes its high h’iVTR to manage exudate.

with different properties. However, the general conclusion is that the thin films have not succeeded in incorporating a wide enough variety of ideal microenvironmental characteristics regarded as approaching the

optimal wound dressing. Hydrocolloids The term &dquo;hydrocolloid&dquo; is commonly used to describe a family of wound management products manufactured from gel-forming agents combined with elastomers and adhesives, applied to a carrier typically consisting of a sheet of polyurethane foam or film (Table 13).

Figure Ilb. hiechanism of action of Biobrane, nylon-reinforced silicone rubber thin film wound

dressing. Downloaded from jba.sagepub.com at SIMON FRASER LIBRARY on November 8, 2014

169 Table 73.

Hydrocolloid products currently available.

Hydrocolloid sheets are widely used in the management of many different types of wounds, including leg ulcers, burns, donor sites and decubiti, but their poor water vapor transmission rates tend to restrict their use to the management of deep wounds, that are moderately exudating. For wounds that produce large amounts of exudate, other hydrocolloid formulations are available, such as granules and pastes, which may be used alone or in combination with the sheets to provide enhanced fluid handling capacity. Hydrocolloids are constructed from a polymeric backing onto which is adhered a hydrocolloid adhesive mixture (Figure 12). The hydrocolloid mixture generally consists of gelatin, pectin, and carboxymethylcellulose. Blended into this layer is a mineral oil and rubber adhesive. This facilitates attachment of the dressing to the wound site. The resulting structure is considerably thicker than thin film devices. The mechanism of action for a hydrocolloid dressing is shown diagrammatically in Figure 13. Hydrocolloid dressings have little moisture vapor transport capability (Figure lla), and rely on the absorption capacity of the hydrocolloid layer to absorb large amounts of exudate. The maximum quantity of ex’ udate which a dressing of this type can manage is a function of the amount of hydrocolloid coating present. Once the maximum absorption limit is reached, the hydrocolloid ceases to aid in this part of wound

healing. ’

An increase’ in the hydrocolloid layer, either in size or thickness, results in a greater exudate absorption capacity. However, as the dressing increases in thickness it becomes significantly less comformable. Conformability is an important issue, as many of these types of wound dressings are used on dermal ulcers, which commonly occur around pressure and flex points, such as heels, ankles and elbows. The lack of Downloaded from jba.sagepub.com at SIMON FRASER LIBRARY on November 8, 2014

170

Figure 12. SEM of the

cross

section of a

hydrocolloid dressing-DuoDerm.

easy conformation can make it difF~cult to maintain the wound dressing

the wound site. A major clinical drawback to hydrocolloid dressings is that after absorbing large quantities of exudate, the .hydrocolloid layer dissolves and contaminates the wound. This gelatinous material has to be subsequently removed at the next dressing change. The removal of this gelatinous material is a time consuming (and thus expensive) process and may damage the healing wound site. The mechanism of exudate control of the hydrocolloid wound dressing, absorption, should be compared with the minimal moisture vapor transport mechanism, which is the sole mechanism of action for thin on

Figure 13. Mechanisms of action of a hydrocolloid wound dressing-Duvl~erm. Downloaded from jba.sagepub.com at SIMON FRASER LIBRARY on November 8, 2014

171 Table 74. Gel products

currently available.

film dressings. In the short run hydrocolloids are much more successful with exudate, but they fail once their absorptive capacity has been reached. -

Hydrogels variety of hydrogel dressings available (see Table 14). They hydrogel materials which are often supplied on an impermeable polymeric backing sheet (Figure 14). The presence of the backing sheet prevents the hydrogel from dehydrating and desiccating the underlying wound. Hydrogels are supplied in a partially hydrated form, which allows for subsequent absorption and further hydration by absorption of wound exudate. Gels are similar to hydrocolloid dressings There

are a

are

in their management of exudate as these materials have little or no vapor transport capacity (Figure 15). Once they reach the maximum absorptive capacity they can no longer manage exudate and maintain an optimum microenvironment. Due to the fact that hydrogels are supplied in a partially hydrated state, they-are not supplied with a pressure sensitive adhesive coating.

Figure 14. Light microscopy cross

section of a

hydrogel dressing-Vigilon.


172

Figure

15. Mechanism of action of a

hydrogel wound dressing-Vigilon..

taping or application of a secondary dressing is therefore required to assure adequate attachment. In addition, hydrogel dressings, after absorption of moderate quantities of exudate, swell and change their physical parameters. The swelling results in the dressing moving away from the wound bed and providing potential air spaces or pockets in which bacteria may proliferate. In some instances, manufacturers recommend that the impermeable backing sheet be removed during the healing sequence on heavily exuding wounds. The removal of the sheet encourages the dehydration of the hydrogel, which moderately increases the dressing’s ability to handle levels of exudate. During dehydration, however, the hydrogel becomes noncompliant and often results in damage to the underlying wound. Lastly, hydrogel wound dressings generally do not dissolve and

Further

contaminate the wound in a fashion similar to hydrocolloids. Gel dressings when hydrated are considered conformable. They have a higher degree of conformability than the fairly rigid hydrocolloid products, but significantly less conformability than thin film dressings. A subset of gel dressings are the alginate gel materials, e.g., Kaltostat. These products are supplied as a dry, fibrous, mat structure. Alginate dressings are capable of absorbing large quantities of exudate. During absorption they undergo a gelation reaction due to the interchange of sodium and calcium ions between the wound bed and the dressing. As in the case of the hydrogel dressings, alginates require the use of secondary dressings to secure them. Foams

Foam dressings typically are manufactured from hydrophilic polyurethane foams [such as Epi-Lock (Figure 16)] except SILASTIC®3, SILASTIC is 3

a

tradename of Dow Corning,

Midland,

MI.


173


cross

section of a

hydrophilic polyurethane

foam

dressing-Epi-

Lock.

which is a silicone-based foam. The wound contacting side of the dressing exhibits open polymer cells that interconnect with those in the bulk of the dressing (Figure 17). The external (outer) surface consists of smaller cells or in some instances, is sealed either by heating the outer surface or by lamination of an impermeable layer. Wound exudate is absorbed by a &dquo;sponge&dquo; type mechanism into the polymer cells of the foam, and in many instances into the hydrophilic polymer itself, which makes up the solid portion of the foam matrix. The majority of foam dressings are provided without a pressure sensitive adhesive, thus making it necessary for secondary dressings to be used on top of them. This is a cumbersome problem and makes the wound dressing anchoring area much larger than those of products that are self-adhering.

Figure

17. Mechanism of action of a

hydrophilic polyurethane foam dressing-Epi-Lock.


174 Table 15. Foam products currently available.

During the absorption of exudate the hydrophilic foams have a tendency to swell. The swelling may create voids and air pockets between the dressing and the wound bed and once again, as in the case of the hydrogel dressings, these have potential to create areas in which bacteria may proliferate. It should be noted however, that the foam dressings are specialized polymers that utilize both a moisture vapor transport mechanism and an absorption mechanism to control exudate. They perform these activities with a moderate degree of success and thus are a step in the right direction to regulate the microenvironment. Foam dressings are available in a variety of thicknesses. Some are extremely conformable and low profile, whereas others tend to be bulky.

The

higher profile foam dressings provide a level of cushioning that is

not available with other

types of materials.

Alginates

Alginate-based wound dressings have been under investigation for century. Initially, the alginates were endowed with certain magical properties, since they appeared to have hemostatic properties at a time when our knowledge of blood coagulation was minimal. Later, they were avoided because of uncertainties about the potential toxic effects of calcium absorption from the dressings. In addition, alginates are expensive and difficult to manufacture in a consistent manner. The major ingredient in these dressings is alginic acid, which is extracted from certain species of brown seaweeds. The alginic acid is converted to an insoluble calcium salt during the manufacturing process. over a

.

~

Table 7fi.

Alginates currently available.


175 One of the best-known alginates is Sorbsan, which has been used in Europe since 1985. Sorbsan is available as a free powder for packing very deep wounds, or as a flat non-woven pad designed to dress more superficial wounds. During use, the alginates swell and form a soft gel as wound exudate is absorbed. Calcium ions are replaced by sodium ions from the exudate. The liberated calcium ions aid in blood coagulation. The non-adherent gel is removed by irrigation with sterile saline. Another well-known alginate is Kaltostat, a product based on natural calcium alginate fibers. This dressing is effective on postsurgical wounds, lacerations, and highly exudating chronic lesions, such as pressure sores and leg ulcers. SECOND GENERATION l~IICROENVIRON1VIENTAL WOUND DRESSINGS

Second generation microenvironmental wound dressings have two properties which differentiate them from first generation products: (1) spyrosorbency and (2) tryptosorbency. Spyrosorbency refers to the dual absorption and breathable mechanism observed in hydrocolloids and thin films in one dressing. Tryptosorbency refers to the dual hemostatic and breathable mechanism observed in calcium alginates and thin films in one dressing. MITRAFLEX114 -A SPYROSORBENT WOUND DRESSING

MITRAFLEX is a second generation spyrosorbent microenvironmental wound dressing introduced in early 1990 [381. It utilizes the molecular and physical characteristics of polyurethane films and microporous membranes to achieve a breathable, absorbent, low profile, conformable, adhesive structure (Figure 18a). MITRAFLEX wound dressing consists of three distinct layers (Figure 18b), each specifically engineered to produce a blend of new features which provide an optimal microenvironment for moist wound healing. The dressing com. bines the moist wound environment properties of film dressings with the absorptive qualities of hydrocolloid in a structure that is both adhesive and conformable. The wound contact surface consists of a porous, pressure sensitive adhesive. The adhesive is attached to a middle-layer, absorptive, polyurethane membrane. Each of the layers of MITRAFLEX have been engineered to provide a specific mechanism of action. The membrane is laminated to a thin, transparent, hydrophilic, polyurethane film. The 4MITRAFLEX is

a

tradename of Polyl4iedica, Woburn, MA.


176

Figure 18a. Features of MITRAFLEX spyrosorbent wound dressing. is supplied on a siliconized release paper. MITRAFLEX trilaminate structure is adhesive, absorptive, and breathable. It is intended for use in the management of dermal ulcers, donor sites, superficial burns, abrasions and lacerations.

complete wound dressing

MITRAFLEX-Component Description Porous Adhesive-Lower Layer The attachment of MITRAFLEX wound dressing to the wound site is accomplished by a pressure sensitive acrylic adhesive (Figure 19). The adhesive layer is molecularly tailored to possess a degree of hydrophilicity. The level of hydrophilicity is such that when placed on a moist wound, the adhesive layer will hydrate in a predictable fashion. When hydrated, the adhesive properties are reduced. A three-dimensional conformaiional change takes place within the adhesive over the wound site and the material loses its tack. This feature allows the easy removal of the dressing from the wound site without damage to the regenerating epithelial surface.

Figure 18b. The trilaminate construction of MITRAFLEX. Downloaded from jba.sagepub.com at SIMON FRASER LIBRARY on November 8, 2014

177

Figure 19. MITRAFLEX components-porous adhesive.

Membrane-Middle Layer The middle layer consists of a newly developed polyurethane microporous membrane (Figure 20). The polyurethane used in the middle layer has been synthesized to possess a specific hydrophilic/hydrophobic balance of properties. The membrane is manufactured by a controlled

Absorptive

phase separation process (Figure 21). A phase separation process consists of forming a polymer solution in a suitable solvent, which then is cast onto a substrate to the desired thickness. The substrate and polymer solution are immersed in a precipitant bath. The bath is ideally a nonsolvent for the polymer, however, it should also be totally miscible with the solvent in which the polymer is dissolved. The resultant process results in a controlled precipitation. The rate of precipitation is a function of the thermodynamics of the polymer solution and its interaction with the precipi. tant bath.

Parameters such as polymer concentration and the type, temperature, and concentration of the precipitant bath each have substantial effects

on

the precipitation rate. The control of the rate of precipitation

Figure 20.

MITRAFLEX

components -absorptive membrane.


178

Figure 21. Phase separation process (coagulation) for the formation of microporous membranes.

allows the manipulation of the structural morphology. This enables the manufacturer to obtain a desired pore geometry. In the case of MITRAFLEX the geometry is determined in advance to optimize absorption and management of the constituent elements of wound exudate. Thus it runs from being macroporous near the adhesive to being microporous at the contact point with the upper layer. Such asymmetric structures, running from macroporous to microporous, may be manufactured on a continuous basis. A schematic diagram of this process is shown in

Figure

22. The blended polyurethane solution is prepared at the desired concentration in a solvent and applied to a moving belt. The belt contain-

Figure 22. Diagram of membrane casting equipment. The three major operations are: (1) coagulation, (2) washing, and (3) drying. Downloaded from jba.sagepub.com at SIMON FRASER LIBRARY on November 8, 2014

179

ing the polymer solution is allowed to pass through a precipitation bath subsequent extraction and washing. After precipitation and ex-

with

traction, the middle membrane is dried. In MITRAFLEX membrane, the polymer utilized in the precipitation of the middle membrane differs in its degree of hydrophilicity from that composition of polyurethane utilized to manufacture the transparent, thin film of the upper layer. The optimum level of virtual crosslinking has been attained by the adjustment in the polymer’s molecular structure to obtain the desired rate of precipitation which results in the desired asymmetric structure. The resultant membrane is a structure with large vertical &dquo;fingerlike&dquo; voids, that taper from the wound surface toward the outer side of the dressing (Figure 23). Between these larger voids are a series of smaller pores that interconnect. The inter-connecting substructure facilitates the lateral transport of exudate. The level of hydrophilicity of the membrane is designed to allow the large interstitial voids to be wettable by exudate without swelling. This avoids the problems associated with the swelling and shape changes associated with gels.

Transparent Film- Upper Layer The upper (air-side) layer of MITRAFLEX is manufactured from a breathable, transparent, polyurethane film (Figure 24). It is highly flexible and allows moisture vapor to be transported through the film while the wound dressing remains impermeable on its exterior to liquids. The upper layer has a monolithic structure which ensures the film is impermeable to microorganisms. The molecular structure of this polyurethane film has a series of in-


cross

section of MITRAFLEX wound

dressing.


180

Figure 24. MITRAFLEX components-transparent &dquo;intelligent&dquo; top film.

teresting and desirable features with respect to wound management. The chemical composition of the upper layer has been molecularly tailored to give the desired level of hydrophilicity. Further, by employing molecular engineering techniques, it has been possible to synthesize a polyurethane which possesses a coil-like molecular conformation. This has been achieved by the manipulation of the level of virtual crosslinking present in the polyurethane blend. In general, polyurethanes, such as those used in the manufacture of MITRAFLEX spyrosorbent wound dressings, can be categorized into two major classes: thermoplastics and thermosets. Thermoplastic polyurethanes are linear segmented structures with no intentional crosslinking inherent in their structure. These materials are heat moldable and processable, they are soluble in organic solvents, and they possess a range of mechanical properties. Thermoset polyurethanes are intentionally branched, segmented structures, which possess a high level of covalent crosslinking. As a result, they are non-heat processable, and are not soluble in organic solvents, although they&dquo;still possess a range of mechanical properties. The presence in polyurethanes of the urethane and urea bonds makes a secondary level of molecular interaction possible (Figure 25). These interactions are caused by the association of the various electrically charged species present along the backbone of the polymer. These short range interactions have a high degree of &dquo;hydrogen bond&dquo; character, and are often referred to as virtual or pseudo crosslinks.. The chemical groupings which may participate in virtual crosslinking are shown diagrammatically in Figure 26. These interactions take place both within and between polymer chains. By adjusting the quantity and type of chemical groupings in the polymer chain, it is posDownloaded from jba.sagepub.com at SIMON FRASER LIBRARY on November 8, 2014

181

Figure 25. Chemical groups found in poly(urethane-urea) polymers.

sible to manipulate the level of virtual crosslinking within the molecule. This allows a level of control over the conformation of the polymer when in the bulk phase. Virtual crosslinking may be enhanced by the presence of hydrogen bonding molecules such as water. Water assisted virtually crosslinked polyurethanes have been developed for MITRAFLEX (Figure 27). These polyurethanes become stronger when hydrated or saturated with hydrogen bonding liquids. Thus MITRAFLEX actually becomes stronger when it is wet with exudate from the wound site. Virtual crosslinks are approximately 1/20th of the normal covalent bond strength, and may be formed and broken an infinite number of times. This ability to be formed and broken provides strong conformable polymers with high flex lives. What it means for a wound dressing is that MITRAFLEX can respond in an intelligent fashion, over and over again, to the changes taking place in the wound site during the

.

healing process. - The density of the virtual crosslinks and their positioning in the polyurethane chain used to manufacture the transparent film of MITRAFLEX, has been designed to facilitate the desired degree of vir-

Figure 26. Possible sites

for virtual

crosslinking in poly(urethane-urea) polymers.


182

Figure 27. Water-assisted virtual crosslinking.

crosslinking so as to enable the molecules to attain a coiled conformation. This formation and retention of the coil conformation is assisted by the presence of hydrogen bonding materials such as water in the exudate (Figure 28). Virtual crosslinking may be controlled by factors such as the type of polyurethane extension agent, the type, the molecular weight, and stoichiometry of the macroglycols used in the synthesis of the polymer. The theorized polyurethane conformation is such that when equilibrated with a hydrogen bonding liquid such as water, a molecular bridging reaction occurs. When fully hydrated the polyurethane adopts a coiled conformation. The coils maintain their conformation by the bridging reaction of the water molecules. The presence of the coiled molecules in the film allows small charged molecules such as water to tual

Figure 28. Virtual becomes stronger in

crosslinking interactions affect polymer conformation (polymer H-bonding liquids; enhanced transport properties).


183

Figure 29. Enhanced transport of water vapor through polyurethane alpha-helical structure.

through the center of the coil thus passing through the film at an increased rate (Figure 29). On dehydration of this structure the coils partially collapse at a determinable rate. The collapse of the coils hinders the movement of water molecules through the film. This is the basis of the intelligence of the MITRAFLEX wound dressing. The practical outcome of the change in conformation between hydrated and nonhydrated conditions is that a differential moisture vapor transport is observed between these two states (Figure 30). The differential moisture vapor transport rate is useful in monitoring whether a wound is highly exuding or only minimally exuding. The mechanism of MITRAFLEX provides a wound dressing which when placed on a highly exuding wound will increase its moisture vapor transport rate to manage the increased amount of exudate. As the healing process progresses the wound may well produce lower quantities of exudate. MITRAFLEX, in response to reduced levels of exudate production from the wound site, becomes less hydrated and as a result, will reduce its moisture vapor transport rate. The ability of MITRAFLEX to monitor the level of exudate coming pass

.


184

from a wound enables the wound dressing to cope with both large and small quantities of exudate while maintaining a moist wound healing environment. This mechanism allows the construction of a wound dressing that is extremely thin and conformable, yet able to control large or small quantities of exudate. As well as being permeable to moisture vapor, the transparent upper layer is permeable to gases, such as CO, and OZ . Thus the &dquo;spyro&dquo; part of the spyrosorbent wound dressing category is the breathability associated with correct permeation of gases..0utward release of C02 from the wound site is a big step in eliminating the unpleasant smell often associated with hydrocolloid wound dressings. The inward flow of 0, can also have beneficial impact on the elimination of anaerobic bacteria within the wound. This overall gas exchange helps to maintain the correct microenvironment for wound healing.

MITRAFLEX-Mechanism of Action Each layer of MITRAFLEX has a specific mechanism of action that combines to form the spyrosorbent wound dressing product. The maintenance of a proper microenvironment for optimal wound healing operates in the following fashion (Figure 31).

Figure

30. MITRAFLEX

MVTR-upright and inverted cup.


185

Figure 31. MlTRAFLEX-mechanism of action.

&dquo;

When placed on an exuding wound, the exudate passes through the macroporous adhesive and into the finger-like voids of the microporous membrane. During this absorption process the areas of adhesive which are in contact with the wound bed slowly hydrate reducing the tack of the adhesive. This allows the dressing to be removed from the wound site without risk of damage to reepithelialized skin. We should note that exudate varies greatly from wound to wound. Abrasion and laceration wounds exude large quantities of blood and serous fluids. Dermal ulcers, on the other hand, tend to exude copious quantities of relatively thick gelatinous, pus-like materials. More than 95% of the exudate composition is water. It is this aqueous portion of the exudate that is allowed to permeate through the upper film of MITRAFLEX into the surrounding atmosphere. Due to the differential moisture vapor transport properties of the upper polyurethane film, as discussed above, the moisture vapor transport rate of MITRAFLEX will be greater when the quantity of exudate from the wound is similarly of a high level. This type of dressing may also be used on a wound producing little exudate. The moisture vapor transport rate of the film in this instance will be reduced, thus preventing desiccation of the wound. The differential moisture vapor transport property of the outer film gives the wound dressing a level of intelligence and enables the dressing to manage a wide variety of exudate types and levels. The transparent properties of MITRAFLEX enable the clinician to observe the absorbed exudate in the membrane layer without the requirement to disturb or remove the dressing. This &dquo;VisudateThl&dquo; capacity overcomes many clinicians resistance to non-transparent

dressings. Downloaded from jba.sagepub.com at SIMON FRASER LIBRARY on November 8, 2014

186 CLINICAL APPLICATIONS OF SPYROSORBENT WOUND DRESSINGS

Intelligent, second generation microenvironmental wound dressings applicability in clinical practice. These dressings are

have found wide

particularly useful in the management of abrasions and dermal ulcers. Although these types of wounds differ widely in terms of the type and quantity of exudate produced, they can each be treated effectively with spyrosorbent wound dressings. The following clinical case studies highlight the versatility of this type of dressing. Clinical Case Study 1

’

patient shown in Photograph 1 has suffered a traumatic injury commonly called a &dquo;road rash&dquo;. A &dquo;road rash&dquo; is typically composed of a

- The

Photograph

1. Case

study

1. &dquo;Road rash&dquo;: initial

presentation of injury.


187

Photograph 2. Case study 1. &dquo;Road rash&dquo;: completed dressing application.

mixture of dermal abrasions, contusions and lacerations. This was caused by the patient falling from a motorcycle. There are deep wounds both on the forehead and underneath the nose. This type of injury is commonly contaminated with extraneous debris which must be removed prior to the application of the dressing. The wounds were cleansed and treated according to the normal protocol of the emergency room. Upon achievement of hemostasis the wound was dressed, as shown in Photograph 2, with MITRAFLEX spyrosorbent wound

dressing. It is interesting to note that abrasion type wounds produce exudate which is mainly composed of blood and serous fluid. This production of exudate occurs early during the healing process. Under these circumstances the wound dressing has a requirement to manage the excess exudate rapidly so as to prevent &dquo;pooling&dquo; of the exudate under the dressing. It will be appreciated that for such facial wounds, flexibility and conformability of the dressing is a primary requirement. When the dressing of the wound. was completed the patient was allowed to return home. The dressings were left in place for four days, at which time they were removed under the guidance of the attending physician. Photograph 3 shows the condition of the wound bed at day four. Good Downloaded from jba.sagepub.com at SIMON FRASER LIBRARY on November 8, 2014

188

reepithelialization of the cheek wounds has occurred, and healing has

been initiated in the deeper wounds wounds were redressed with further

on

the forehead and lip. The of spyrosorbent wound

pieces

dressing. At seven days post injury, the patient returned for a second time. Upon removal of the wound dressings good healing of the cheek abrasions was observed and also of the deeper wounds on the forehead and lip (Photograph 4). Throughout the treatment period, the exudate was properly managed simultaneously with maintaining an optimal moist wound healing microenvironment. The overall result was a faster healing wound with minimal scarring. Throughout this period the patient required only small doses of oral acetaminophen therapy, rather than potent prescription analgesics, such as percocet or opioids.

Clinical Case

Study 2

The previous case study exemplified how spyrosorbent wound dressings may be used for traumatic abrasion wounds. The versatility of spyrosorbent wound dressings also allows them to be used effectively in the management of problem chronic wounds such as dermal ulcers.

Photograph

3. Case

study

1. &dquo;Road rash&dquo;: four

days post injury.


189

Photograph 4. Case study dermal repair.

.

1. &dquo;Road rash&dquo;: seven

days post injury showing near complete

Photographs 5-9 show the progressive healing of a venous stasis ulcer which was treated with MITRAFLEX spyrosorbent wound dressings. These types of wounds exude at varying rates and do so at different time intervals during the healing sequence. It should be remembered that the underlying clinical ailment which has led to the formation of the ulcer is chronic. Hence, in these types of patients further lesions will undoubtedly occur at other positions on the patient. Photograph 5 shows the initial ulcer prior to treatment. The ulcer was cleaned and covered with a spyrosorbent wound dressing. The dressing was left in position for 7 days. Photograph 6 shows the wound at 7 days with the dressing removed. It will be noted that the size of the wound has increased over that shown in the initial photograph. This is due to the fact that the wounddressing has created a moist microenvironment which has facilitated the natural enzymatic debridgement process to occur. The wound, at this stage, has now cleansed itself and is showing early signs of granulation.

-

The lesion was redressed and examined after a further 7 days. This is shown in Photograph 7. At this time both the area, and the depth of the wound have been reduced. Dermal lesions of this type are often deep Downloaded from jba.sagepub.com at SIMON FRASER LIBRARY on November 8, 2014

Photograph 5. Case study

2. &dquo;Dermal ulcer&dquo;: initial condition of lesion.

Photograph 6. Case study 2. &dquo;Dermal ulcer&dquo;: condition after 1 week treatment with MITRAFLEX spyrosorbent wound dressing. 190


191

7. Case study 2. &dquo;Dermal ulcer&dquo;: wound condition after 2 weeks treatment with hIITRAFLEX spyrosorbent wound dressing.

Photograph

.

and require the body to &dquo;fill-in&dquo; the wound prior to the surface being reepithelialized. The remaining photographs in the series show the progression of wound healing at 7-day intervals with the wound being treated with MITRAFLEX during these periods. Photograph 9 shows the lesion when fully healed. Dermal ulcers produce exudate in an erratic manner. The capacity of intelligent spyrosorbent wound dressings to monitor and adjust their moisture vapor transport rate in response to the level of exudate production is of prime importance in this particular application. Similarly, the low profile and conformable properties of spyrosorbent wound dressings are essential when used on these types of lesions, as they normally occur on pressure points and points of flexure. SPYROFLExnrs-A TRYPTOSORBENT WOUND DRESSING

SPYROFLEX belongs to the tryptosorbent

family of wound dresshas to meet the requirements of ings. It been designed specifically bleeding wounds. As a result, it exemplifies what may be accomplished SPYROFLEX is 5

a

tradename

of PolyMedica, Woburn, MA.


Photograph

8. Case

study

2. &dquo;Dermal ulcer&dquo;: wound condition after treatment with

MITRAFLEX.

Photograph 9. Case study 2. &dquo;Dermal ulcer&dquo;: ment with MITRAFLEX. 192

closed, healed wound after 5 weeks treat-


193 molecular engineering to produce tryptosorbent dressings, and also embodies many of the ideal characteristics of a microenvironmental dressing listed in Table 8. SPYROFLEX is fabricated from proprietary polyurethane formula. tions. The polymeric materials are manufactured into microporous membranes by a phase separation process utilizing controlled coagulation techniques. The resultant membranes are coated with a pressure sensitive adhesive system which is applied to produce a dot matrix pattern. The dressing is supplied on a siliconized paper release liner. These dressings have found application in the treatment of bleeding wounds such as donor sites and traumatic abrasions. They have also found utility as wound closures particularly in the closure of lacerations and incisions. During clinical trials it was determined that SPYROFLEX exhibited &dquo;styptic’ properties which has led to its description as a &dquo;tryptosorbent&dquo; wound dressing, i.e., one that tends to

utilizing

check

bleeding [391.

SPYROFLEX- Component Description Adhesive Layer The adhesive system utilized on SPYROFLEX has a degree of con. trolled wound bed adhesion. The portion of the adhesive that lies in contact with the wound bed slowly hydrates, thus reducing the tenacity of the dressing’s adhesive characteristics. SPYROFLEX is a bilaminate structure consisting of a microporous polyurethane membrane coated with a pressure sensitive adhesive (Photograph 10). As shown in the .

Photograph 10. Scanning electron micrograph comparing the trilaminate MITRAFLEX with the bilaminate SPYROFLEX ultrastructures. Downloaded from jba.sagepub.com at SIMON FRASER LIBRARY on November 8, 2014

194

Photograph 11. Macroporous adhesive of SPYROFLEX showing the &dquo;cross-hatch&dquo; pattern.

Scanning Electron Micrograph, the nonwound contacting surface

con-

sists of a nanoporous integral skin that is impermeable to bacteria. The &dquo;cross-hatched&dquo; patterned adhesive allows the passage of exudate and moisture vapor directly into the bulk of the membrane. The membrane pores themselves connect laterally so as to provide a much greater surface area from which the aqueous portion of the exudate may evaporate. The overall structure is thin and elastomeric which provides a very high level of flexibility and conformability The wound contact surface of the membrane consists of large conical voids. These two surfaces are separated by an asymmetric structure with graded porosity The wound contact surface is coated with a &dquo;crosshatch&dquo; pattern of an acrylic pressure sensitive adhesive (Photograph 11). Coverage is such that approximately 50% of the dressing’s surface pores are exposed to the wound. This has been accomplished by the judicious choice of manufacturing parameters during the membrane formation process. SPYROFLEX membranes are manufactured by a phase separation process utilizing a liquid coagulation technique. The essential elements of this process are that a polymer solution is spread onto a moving belt. The belt and polymer solution are then passed through a bath Downloaded from jba.sagepub.com at SIMON FRASER LIBRARY on November 8, 2014

195 of liquid. The coagulation bath is composed of a liquid which is a nonsolvent for the polymer and which is miscible with the polymer solvent. The structure of the membrane produced may be manipulated by the desired choice of solvent and nonsolvent. More rapid precipitation leads to an asymmetric structure, while a slower coagulation rate produces more uniformly microporous materials [40].

SPYROFLEX- 31echanism of Action

Properties of SPYROFLEX Laboratory studies have been conducted to elucidate the integrity of the barrier properties of SPYROFLEX. These studies have used bacterial penetration techniques to determine its integrity. The asymmetric

Barrier

structure of SPYROFLEX contains

a nanoporous &dquo;skin&dquo; which while is at a molecular level. It is an obvious rebeing nonporous permeable of a. wound microenvironmental quirement dressing that it must prevent the passage of bacteria to the wound site. This helps eliminate the likelihood of wound contamination and infection from external sources. It is also important that the dressing itself not provide a growth medium for bacteria as is the case with hydrocolloid products.

Microbial Penetration Studies Microbial penetration studies were performed on SPYROFLEX using both S aureus and E. coli. S aureus was chosen as representative of gram positive nonmotile bacteria. It is also of clinical significance in that it is a common opportunistic pathogen present in infected wounds. E. coli was chosen to represent gram negative motile bacteria. E. coli is significant in terms of possible poor hand hygiene. Samples of wound dressing were placed on a Tryptone Soya Agar (TSA) plate, which had been previously moistened with a small quantity of nutrient broth. A drop of the respective test organism obtained from an overnight culture in nutrient broth was placed on top of the wound dressing to cover an area of approximately 1 cm2. The testing apparatus used is shown in Figure 32. Each test sample was incubated at 37 ° C and inspected for signs of bacterial growth at 1, 2, 3 and 7 day intervals. At the seventh day, the wound dressing was removed and the agar plate alone incubated for a further 24 hours to ascertain whether penetration of bacteria had taken place. The experimental procedure also included control samples. The positive control utilized a piece of similar wound dressing which had been mechanically pierced to provide an easy passage for bacteria. A negative control utilized a thin film dressing (OpSite) which being a continuous film is an absolute bacterial barrier. Downloaded from jba.sagepub.com at SIMON FRASER LIBRARY on November 8, 2014

196

Figure 32. Apparatus used to determine bacterial penetration of wound dressings. The results of this analysis are set out in Table 17. The data indicates that SPYROFLEX’s nanoporous skin is a barrier to bacterial penetration.

Conformability

.

’

It was mentioned that SPYROFLEX is highly conformable to difficult body contours. Comparative conformability to existing thin film and hydrocolloid dressings has been determined by a standard laboratory test. Conformability of a two-dimensional isotropic material can be measured by subjecting the material to differential pressure and measuring the material’s degree of deformation. In the case of wound dressings a pressure of 40 mm Hg was used as the test pressure, this being the pressure under which peripheral blood flow is maintained in the body. The results, displayed as radius of curvature vs. the height of the dome (deformation) are taken using the following expression: 2

R = DD2 8x2 ++ 2x D ~ ~

_

_x

R being the radius of curvature, D the diameter of the test specimen, and x the height of the dome (measured 1 minute post pressurization). A series of thin film and hydrocolloid dressings were tested in this Downloaded from jba.sagepub.com at SIMON FRASER LIBRARY on November 8, 2014

197 Table 77. Bacterial barrier

*

testing data.

S.a. Staphylococcus aureus E.c. - Escheria coli + - Bacterial penetration observed No bacterial penetration observed -

-

-

fashion and compared with SPYROFLEX. The results of this analysis are set out in Figure 33. It can be clearly seen that SPYROFLEX has a similar degree of conformability as the thin film dressings (Op-Site and Tegaderm), and is dramatically more conformable than the hydrocolloid DuoDerm.

Figure 6Bioclusive is

a

33.

Conformability determinations of selected wound dressings.

tradename of Johnson & Johnson, New

Brunswick, NJ.


198

Tryptosorbent Performance Characteristics Clinical evaluations of SPYROFLEX were performed on several types of bleeding wounds. A particularly useful wound type to study found to be donor sites. These are controlled-thickness wounds inflicted by a physician under clean conditions. SPYROFLEX has been designed to be used on this type of wound as exemplified by the case study shown in Photographs 12-14. In this particular instance, a pediatric patient had a donor site wound inflicted on his upper leg. The tissue removed during this procedure was subsequently used to reconstruct a burn on the back of the patient. The wound was dressed with SPYROFLEX. This provided a moist microenvironment under which optimal wound repair could proceed. The maintenance of a moist microenvironment practically eliminated the pain and discomfort normally associated with donor site wounds. It was noted by clinical investigators that the dressing exhibited styptic properties, i.e., the dressing had a tendency to check the bleeding. was

Hemostasis In the event of excessive bleeding the body has developed a complex mechanism by which bleeding is checked and ultimately curtailed. This mechanism is termed coagulation.

Photograph 12. Case study 3. &dquo;Pediatric donor site&dquo;: initial presentation of donor site. Downloaded from jba.sagepub.com at SIMON FRASER LIBRARY on November 8, 2014

Photograph 13. Case study 3. &dquo;Pediatric donor site&dquo;: dressed with SPYROFLEX.

Photograph operatively.

14. Case

study

3. &dquo;Pediatric donor site&dquo;: site healed


sever

days post-

199

200

Blood is transported around the circulation system under pressure. Should a blood vessel be damaged, blood will escape until there is an equalization of this pressure. The equalization of pressure may be obtained by the accumulation of blood in the surrounding tissue spaces, i.e., by the formation of a hematoma, or after a fall in blood pressure due to blood loss. When large vessels are damaged it is often required that hemorrhaging be stopped by the use of artificial techniques such as tourniquets. Most surgical and traumatic bleeding is due to the rupture of relatively small blood vessels. The body’s natural defense to this damage is to activate vessel constriction. Under normal circumstances there is little tendency for platelets to adhere to each other. Following mechanical damage, however, platelets adhere to the site of damage and tend to stick to one another. This process seals minor vessels. The platelet aggregation together with the vasoconstriction helps to attain hemostasis. The platelet aggregate is reinforced at a later stage by the formation of fibrin. The contact of platelets with damaged tissues or exposed collagen fibers leads to the release of many platelet factors. After several minutes, activation of the coagulation cascade results in fibrin deposition and formation of a clot-which helps to form a hemostatic seal. This clotting procedure is the result of a chain of enzymic reactions whereby a soluble plasma protein, fibrinogen, is transformed into a network of molecules of fibrin. The conversion is brought about through the enzyme thrombin which cleaves a specific portion of the fibrinogen molecule. This portion then polymerizes and forms strands of fibrin. The process is accelerated in the presence of calcium ions. At the completion of the formation of a hemostatic blood clot, fibroblasts grow into the clot and form a permanent connective tissue seal. A diagrammatic representation of the coagulation cascade is set forth in Figure 34. In the coagulation cascade a variety of precursors are present in plasma which when stimulated by the act of damaging a wound, react in a sequential fashion. There are two major systems present: the intrinsic and extrinsic systems. They both, however, have a final common pathway which leads to the ultimate formation of fibrin [41,42]. Normal clinical methods to control bleeding include the application of pressure, which frequently stops bleeding after compression is maintained for several minutes. Packing of wounds may also be necessary. This assists in maintaining pressure over a longer period than may be possible by manual application of compression. Clamps and ligatures are also often used on the medium to large blood vessels, however, caution should be exhibited as damage due to clamping pressure often occurs. Electrocoagulation is used for both cutting and obtaining Downloaded from jba.sagepub.com at SIMON FRASER LIBRARY on November 8, 2014

201

Figure 34. Coagulation cascade showing the interaction of the intrinsic and extrinsic

pathways.

hemostasis. The heat provided in this method provides rapid and effective hemostasis particularly for small bleeding vessels. The other common method for obtaining coagulation is the use of topical hemostatic agents. These may be pharmaceutical in nature such as topical adrenalin, or can be device related as in the case of collagen, gelatin and alginate based materials which may be placed on the wound site. _

In vitro SPYROFLEX In order to

SPYROFLEX,

Styptic Characteristics

the source of the styptic properties of series of in vitro studies were initiated. These in-

identify a

cluded : .

. . . .

extractions in saline whole blood clotting time thrombotest thromboplastin time

platelet aggregation Downloaded from jba.sagepub.com at SIMON FRASER LIBRARY on November 8, 2014

202 These evaluations were designed to identify whether the styptic property is due to a leachable material or is surface mediated.

Extractions in Saline of SPYROFLEX wound dressings were extracted using saline, and their respective weight losses determined. Extracts

Samples isotonic

analyzed by gas chromatography to identify the presence or absence of polar extractable moieties. Results of this analysis are shown in Table 18. The weight loss was within the error of measurement. It was concluded that there were no leachable materials present in the dressing. This would signify that the dressing itself is responsible for the styptic properties rather than a small molecule extractant. ’Ib the patient, this means that no systemic coagulation effects can interfere with other medications being administered. were

Whole Blood

Clotting Time (WBCT)

Whole blood clotting time

was

determined

using SPYROFLEX and

two other wound dressings: a thin film and hydrocolloid. The method used was that of Lee and White [43]. ’~s~ tubes containing samples of test material (a blank test tube was used as the control) were warmed to 37°C in the water bath. Blood was withdrawn into a syringe, and then immediately aliquoted into a set of test tubes containing samples of test material. The time of formation of a clot was taken as the WBCT. The whole blood clotting time is a non-specific test, but gives an indication as to whether any of the various clotting pathways have been stimulated, so giving a shorter clotting time. The results are tabulated in Table 19. The data indicates that blood clots faster when in contact with SPYROFLEX than with either the hydrocolloid or thin film dressings. The rate of increase is approximately 20%. We have already established that the styptic effect is not due to an extractable chemical Table 18. Saline extraction of SPYROFLEX and gas (GC) analysis of extractant.

chromatography


203 Table 19. Whole blood clotting time (WBCT) (intrinsic plus extrinsic pathway).

moiety and the whole blood clotting time further suggests the styptic effect to be a surface phenomenon. To the patient this means that hemostasis will be achieved faster in bleeding wounds, thus resulting in faster healing and a shorter hospital stay. Thrombotest (TT)

Experiments to determine whether the extrinsic pathway of coagulation had been activated were performed by subjecting SPYROFLEX to as described by Owren [44]. Citrated whole blood was incubated with samples of test dressings (no dressing was used for the control) at 37°C for 30 minutes. A thrombotest was then performed on the resultant blood to determine if there had been any effect on overall clotting activity after incubation in citrated whole blood. Any decrease in the clotting time for the thrombotest indicates an effect on the extrinsic clotting system. The data from this procedure is presented in Table 20. It shows that there is little effect of SPYROFLEX on the extrinsic pathway. This further supports the premise that this coagulation phenomenon is surface mediated and likely to be more clearly seen by the intrinsic pathway and platelet activation. Similarly, little effect is shown by either the thin film or hydrocolloid dressings under similar conditions. This means that even hemophilic patients can be successfully managed with SPYROFLEX wound dressings.

thrombogenicity testing


204 Table 20. Thrombotest

(extrinsic pathway).

Thromboplastin Time (PTT) The intrinsic pathway determinations were determined by the method described by Longdall et al. [45]. This procedure utilizes a method of determining the partial thromboplastin time. Citrated plasma was incubated, with samples of dressings, (no dressing was used for the control) at 37 ° C for 30 minutes. The resultant plasma was then used in the PTT test to determine to what extent the intrinsic coagulation pathway has been stimulated, particularly the &dquo;contact&dquo; factors. Any decrease in the PTT is an indication of stimulation of the intrinsic coagulation pathway. The data from this testing regime is presented in Table 21, and shows that the intrinsic pathway is actiTable 2~. Partial

thromboplastin

time

(intrinsic pathway).


205

vated by SPYROFLEX and hydrocolloid dressings. The coagulation effect was greater with SPYROFLEX than that observed for the hydrocolloid. Activation of the intrinsic pathway to produce coagulation tends to be slower and more damped than in direct stimulation or clot-

ting via

the extrinsic route.

Platelet Aggregation Studies Platelet aggregation was measured in whole blood using a sequential counting technique [46]. Approximately 5 mls of citrated human blood was placed in a dilu-vial and mixed on a magnetic stirrer. The blood was then aspirated in a whole blood platelet aggregometer. Five 1 CM2 pieces of test material were then added to the blood sample to assess the potential of the material to activate platelets. The blood was aspirated for a minimum of 10 minutes to monitor platelet activity. As a negative control the citrated blood sample was aspirated for a minimum of 10 minutes to monitor any spontaneous aggregation. After ~10 minutes 400 ul of 20 pg/ml ADP was added to the negative control blood to stimulate platelet aggregation. The results in Table 6 show that SPYROFLEX causes platelet aggregation. The effects seen with this testing support the position that a surface activation phenomenon is occurring. This means that no systemic effects are at work. Blood coagulation is induced strictly by surface effects. SPYROFLEX-Additional Applications The aim of traditional wound closure is to restore physical integrity and function of injured tissue with a minimum of deformation and infection. There are three major wound closing techniques:

primary closure delayed primary closure * healing by secondary intention Primary closure is achieved by immediately closing the wound when ~ ~

there is

loss of tissue. This method is used for clean wounds which potential for bacterial contamination. Delayed primary closure is used when a wound is left open following the incision or injury due to significant bacterial contamination. This is often the case in operative incisions which have been made into the peritoneal cavity, urinary tract, plural cavities, and alimentary canal. The superficial wound layers are left open and packed with gauze dressings for a period of four to five days. The elapsed time allows the wound no

have little

or no


206 to develop resistance to infection at which time it may be closed without the risk of infection. It is notable that the presence of foreign material in a wound greatly lowers the threshold for infection. It has been clinically shown that experiments with Staphylococcus aureus when present on a single silk suture could potentially lower the threshold of clinical infection by a factor of 10,000. It has also been found that wounds closed with tapes develop resistance to infection more rapidly than sutured or stapled wounds. This is not surprising as sutures &dquo;implant&dquo; small pieces of epidermis and surface organisms into the deeper dermal layers of the wound by the action of the suturing process.

SPYROFLEX possesses excellent conformability, and unmatched elastic rebound properties. This makes the material an ideal candidate for a wound closure tape. It has found particular utility in the closing of operative incisions, and an example of its use in this area can be seen in Photographs 15 through 18. In case study 4 SPYROFLEX has been used to close the wound formed during an inguinal herniorrhaphy. After this surgical procedure absolute hemostasis was attained. The ends of the incision wound were gently distracted using skin hooks in order to bring the wound into apposition. A piece of SPYROFLEX of the desired size was applied to one side of the wound, the edges placed in correct apposition,

Photograph

15. Case

study 4. &dquo;Inguinal herniorrhaphy&dquo;: operative incision.


Photograph

16. Case

study

4.

&dquo;Inguinal herniorrhaphy&dquo;: manual apposition of the inci-

sion.

Photograph 17. Case study 4. &dquo;Inguinal herniorrhaphy&dquo;: SPYROFLEX wound closure in position maintaining wound apposition. Downloaded from jba.sagepub.com at SIMON FRASER LIBRARY on November 8, 2014

207

208

Photograph 18. Case study 4. &dquo;Inguinal herniorrhaphy&dquo;: operative incision wound-six weeks postoperatively. SPYROFLEX allowed the formation of a thin closure line, with no &dquo;stitches railroad tracks&dquo; prevalent in traditional surgical sites.

and the SPYROFLEX then firmly placed onto the opposite wound edge. During this procedure, the SPYROFLEX was gently stretched to ensure the desired level of closure. No further dressing was used, and the patient was allowed to return to the ward. Approximately two days post operatively, the patient was returned home, and encouraged to mobilize and shower with the dressing in place. SPYROFLEX was left on this wound for a period of seven days. On the patient’s return, the dressing was removed and the wound examined. A further examination was performed six weeks post operatively. As the photographic record indicates, the wound at six weeks had healed well leaving only a thin linear scar with excellent cosmetic results. It is interesting to note the absence of the typical &dquo;railroad track&dquo; lines which are normally observed when sutures are used for wound closure. This feature may be particularly desirable in cesarian sections, cosmetic surgeries, etc. Healing by secondary intention allows the wound to close itself by a process of contraction and epithelialization. It is often used for heavily contaminated and infected wounds, and for extensive superficial wounds with tissue loss, such as donor sites. Case study 3 represents a pediatric patient who required harvesting of a leg skin for transplant Downloaded from jba.sagepub.com at SIMON FRASER LIBRARY on November 8, 2014

209 to the back.

Photographs 12 though 14 visually depict the clinical of this patient. The donor site was healed after 9 days. A more detailed description of a larger clinical evaluation of SPYROFLEX used in wound closure applications has been published by Sommers [47]. SPYROFLEX was found to be an excellent wound closure material which gave good cosmetic results while reducing pain and allowing the patient full mobility during the healing process. course

DISCUSSION

The wound dressing products discussed above provide a first generation moist microenvironment within which the wound may heal. They differ markedly in their user friendly attributes such as conformability, adhesiveness, and ease of use. There is a more dramatic difference in the mechanisms by which they seek to manage exudate. Thin film dressings extensively utilize the moisture vapor transport properties of the polymer materials from which they are manufactured. The thin film category of dressings have also shown that by suitable choice of molecular structure of the film, moisture vapor transport rates may be substantially regulated-i.e., increased or reduced dependent upon the requirements of the dressing. Hydrocolloid and gel dressings each utilize absorption mechanisms which manage exudate. As a result of this absorption, they tend to be thicker dressings than the thin film materials which result in a series of conformability and other problems when utilized in a clinical environment. Foam type dressings utilize both a moisture vapor transport and absorption mechanism to manage exudate. These dressings, due to their chemical nature and high degree of hydrophilicity, tend to swell and lose mechanical integrity when wet. The simultaneous use of a moisture vapor transport and absorption mechanism within one dressing could come very close to optimizing the microenvironment for wound healing. Other desirable attributes are to develop a low profile, high conformability, breathability and an absorptive mechanism which would not have a finite exudate absorption capacity. This last point requires development of new materials to construct a dressing which will adequately manage exudate in relationship to the quantity available while simultaneously providing the optimal moist microenvironment. A second generation wound dressing of this type has been introduced and we shall consider it to be an entirely new class of microenvironmental wound dressing. This new class we shall term spyrosorbents (breathable and absorbent). Spyrosorbent Downloaded from jba.sagepub.com at SIMON FRASER LIBRARY on November 8, 2014

210

wound dressings not only manage exudate by absorption but have the

ability to adjust their moisture vapor transport properties in response to the level of exudate available at the wound site. What this means is spyrosorbent dressings possess a level of active intelligence due to their unique physical and chemical structure. intrinsic

CONCLUSIONS

First generation environmental wound dressings such as those belonging to the categories of thin films and hydrocolloids proved the utility and acceptance of moist wound healing theory. These categories of dressings utilize a passive mode of operation. This typically means that the dressing utilizes only one mechanism of action which may be either an absorptive or evaporative mode. The development of spyrosorbent wound dressing technology has brought a level of intelligence and a degree of interaction of the wound dressing with the healing wound. This has been accomplished by the manipulation of the chemical and molecular properties of polymeric materials together with an understanding of polymer membrane formation processes. We have only just begun to build a level of interactive sophistication into wound dressing devices. The future promises an increase in the number and complexity of intelligent, interactive wound healing

systems. REFERENCES 1. 1989. National Pressure Ulcer

Advisory Panel. Pressure Ulcer’s Prevalence, Cost and Risk Assessment: Consensus Development Conference Statement. Decubitus, 2(2):24-28. 2. Kitka, M. J. and J. J. Schuller, et al. 1988. "A Prospective, Randomized Trial of Unna’s Boots vs. Hydroactive Dressings in the Treatment of Venous Stasis Ulcers;’ J. Vasc. Surg, 7(3):478-483. 3. Banda, M. J. and D. R. Knighton, et al. 1982. "Isolation of a Nonmitogenic Angiogenesis Factor from Wound Fluid;’ Proc. Natl. Acad. Sci. USA. 79:7773-7777. 4. 1989. American 20.

Hospital Association, Hospital Statistics, Chicago, IL,

p.

5.

Ebell, B. 1937. The Papyrus Ebers. The Greatest Egyptian Medical Docu-

6.

Stickel,

Copenhagen: Levin and Munksgaard. D. L. and H. F. Seigler. 1977. "Transplantation. I. Historical Aspects," in Textbook of Surgery, 11th Ed., D. S. Sabiston, ed., W. B. Saunders Company, pp. 456-463. ment.


211 7. Friedman, S. J. and W. P. Su. 1984.

"Management of Leg Ulcers with Occlusive Dressings;’ Arch. Dermatol., 120:1329-1336. Bolton, L., J. Chen and M. Lydon. 1989. "Occlusive Dressings’ Expanding Role in Wound Healing," Second Ann. Symp. on Advanced Wound Care, Poster Session, New Orleans, LA., April 23-25. Wallace, A. B. 1941. "The Treatment of Burns;’ Oxford War Manuals. London : Humphrey Milford. Pickrell, K. L. 1942. "A Sulphonamide Film for Use as a Surgical Dressing," Bull. John Hopkins Hospital, 71:304. Odland, G. 1958. "The Fine Structure of the Interrelationships of Cells in the Human Epidermis;’ J. Biophys. Biochem. Cytol., 4:478-483. Winter, G. D. 1962. "Formation of Scab and Rate of Epithelialization of Superficial Wounds in the Skin of the Young Domestic Pig," Nature, 193:293-294. Hinman, C. D., H. I. Maibach and G. D. Winter. 1963. "Effect of Air Exposure and Occlusion on Human Experimental Skin Wounds" Nature,

Hydrocolloid 8.

9. 10.

11.

12.

-

13.

200:377-379. 14. Rovee, D. T. "Effect of Local Wound Environment on Epidermal Healing," in Epidermal Wound Healing, Maibach and Rovee, eds., Chicago, IL: Year Book Medical Publishers, pp. 159-181. 15. Winter, G. D. 1962. "Formation of Scab and Rate of Epithelialization of Superficial Wounds in the Skin of the Young Domestic Pig," Nature,

16. 17.

18.

19. 20. 21. 22. 23. 24.

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Using SPYROFLEX Membrane


Modern collagen wound dressings: function and purpose.

A Network Approach to Wound Healing.

Wound dressings - a review.

The Wound Microbiome: Modern Approaches to Examining the Role of Microorganisms in Impaired Chronic Wound Healing.

Wound healing: a review. II. Environmental factors affecting wound healing.

Wound healing: a review. I. The biology of wound healing.

Wound infection under occlusive dressings.

Wound healing.

Wound healing.

Attempts to accelerate wound healing.

Wound healing.

Fibrous nanozyme dressings with catalase-like activity for H2O2 reduction to promote wound healing.

Cutaneous wound healing in aging small mammals: a systematic review.

Exploring Wound-Healing Genomic Machinery with a Network-Based Approach.

Wound healing and nutrition: going beyond dressings with a balanced care plan.

Dressings and Products in Pediatric Wound Care.

Wound Dressings and Comparative Effectiveness Data.

Wound dressings and airborne dispersal of bacteria.

[The history of wound dressings (author's transl)].

Stress and wound healing.

Smoking and wound healing.

Angiogenesis in wound healing.

Metalloproteinases and Wound Healing.

microRNA and Wound Healing.