Treatment of burns – established and novel technology

Introduction

Burn trauma is one of the worst injuries suffered worldwide with an incidence of approximately 2 million cases annually [1]. Over the past decades, progress in the treatment of severe burn injuries has significantly decreased morbidity and mortality [2]. The improvements in survival have been most notable in the elderly patient population [3, 4]; however, survival has also improved in severely burned pediatric patients. Four major areas of advancement in burn care have been identified:

Fluid resuscitation and early patient management

Control of infection

Modulation of the hyper-metabolic response

Surgery and wound care.

Because of their extensive wounds, burn patients are chronically exposed to inflammatory mediators and microorganisms. With the advent of early burn wound excision and coverage [5], the risk of serious systemic infection originating from the burn wound has been reduced [6]. The current surgical approach to burn care is based on early excision of full-thick- ness burn tissue followed by early wound coverage, preferably with autologous skin graft. Early excision within the first 48hrs can significantly reduce blood loss and is safe and effective [7, 8]. In order to provide sufficient temporary wound coverage in large burns, allograft or xenograft can provide protection

Marc G. Jeschke et al. (eds.), Handbook of Burns

for many weeks until enough donor sites are available for grafting. In addition, widely meshed autografts have been utilized with allograft or xenograft overlay (sandwich technique) to provide adequate coverage. Repeated autografting can be performed within 7 to 10 days when donor sites have healed [9–11]. This approach, albeit still not implemented in many burn centers around the world, has been practiced for the last quarter century almost without change. During this time period, however, new approaches and devices, such as the use of fibrin sealant for autograft fixation [12, 13], the dermal substitute Integra [14], cultured epidermal autografts (CEA) and cultured skin substitute (CSS) [15, 16], human amniotic [17], Biobrane and similar biodressings [18], and stem cell and gene therapy have been successfully introduced or are currently being studied. This chapter introduces and discusses some of these exciting developments and gives an outlook on new ideas.

Partial thickness burns

Partial thickness burns are divided into superficial and deep categories. The distinction between the two types of partial thickness burns is based on the depth of injury. Superficial partial thickness burns (from accidents such as immersion in an overheated bath tub water, flash flame burns, etc.) are erythematous and painful, blanch to touch, and often blister.

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These wounds spontaneously re-epithelialize from retained epidermal structures in the rete ridges, hair follicles, and sweat glands within 7 to 14 days. After the wound has re-epithalialized, secondary scar maturation takes place that may result in hypoor hyperpigmentation over the long term.

Deep dermal burns into the reticular dermis appear more pale and mottled, do not blanch to touch, but remain painful to pinprick. These burns can take up to four weeks for complete re-epithelialization from the hair follicles and sweat glands, often with severe scarring as a result of the loss of dermis. The epidermal layer in partial thickness burns usually sloughs off, leaving open raw skin with nerve endings exposed. Therefore, partial-thickness burns represent one of the most painful of the several categories of thermal injuries [19].

Historically, partial-thickness burns were treated conservatively by removing the damaged top layer of skin after the initial injury, followed by application of topical medications one to two times each day [20, 21]. These procedures, however, may cause severe pain and anxiety in patients, even with the use of pain medication.

Synthetic and bio-synthetic membranes – biobrane, awbat, suprathel

To improve patient comfort, control infection, and increase the rate of re-epithelialization, alternatives for the treatment of partial-thickness burns have been developed. Semi-occlusive and synthetic membranes are the most important clinically applicable devices. These partly occlusive dressings allow re-epithelialization to occur beneath the dressing and eliminate the need for frequent dressing changes. There are several skin substitutes that are available commercially. Biobrane is a biosynthetic wound dressing constructed of a silicone film with a nylon fabric partially embedded into the film. The fabric presents to the wound bed a comple× 3-D structure of tri-filament thread to which collagen has been chemically bound. Blood and sera clot in the nylon matrix, thereby firmly adhering the dressing to the wound until epithelialization occurs. It controls vapor transfer, maintains a moist healing environment, and has been shown to be effective in the treatment of partial-thickness burns, particularly in pediatric patients, in numerous scientific publications since

1982 [22–28]. A newer biosynthetic product, Awbat , has been cleared by the FDA in 2009 and is now commercially available. Biobrane and Awbat are comparable constructs, as both feature a thin medical grade silicone membrane, good stretchabilty, and pores in the silicone membrane. Both have collagen peptides for the purpose of reacting with the fibrin in the wound to achieve good acute adherence. The main difference between the two membranes is the pore size and regularity – the approximate area of an Awbat pore is 88 sq. mm; the approximate area of a Biobrane pore is about 6.2 sq. mm, with Awbat about five times more porous than Biobrane. The greater porosity of Awbat is expected to result in improved transfer of exudate from the wound surface which may result in better acute adherence, and shorter healing time. As of now, however, there is only limited clinical experience with this new membrane [29, 30].

Suprathel is produced from a synthetic copolymer mainly based on DL-lactide ( > 70%), the other components are trimethylenecarbonate and-caprolactone. The monomers are polymerized by a melting procedure. The final product is a porous membrane with an interconnected structure of pores between 2 and 50 um and an initial porosity of over 80%. It also boasts high plasticity and water permeability. It is applied to the wound bed with an overlay of paraffin or non-adherent gauze, and peels off within approximately two weeks as the re-epithe- lialization of the wound bed progresses [31]. Prospective randomized clinical studies in partial-thick- ness burns and on split-thickness donor sites showed mainly a reduction in pain, with wound healing times and long-term scar qualities comparable to other commercially available membranes [31–33].

Biological membranes – amnion and others

Human amniotic membrane has been used for centuries as a biological wound dressing. In western medicine, amniotic membranes have been used since the beginning of the last century. The first reported use of amnion in burn wounds was by Sabella in 1913, shortly after Davis used amniotic membrane in skin transplantations in 1910 [34]. However, it soon became clear that amnion could not be used as a permanent skin transplant, but only as a tempo-

rary biological wound dressing. Many advantages of amnion as a temporary dressing have been reported, most notably alleviation of pain, the prevention of infection [35–38], acceleration of wound healing [34, 37, 39], and good handling properties [40]. The first use of amnion as a temporary skin substitute in burn wound care has been reported by Douglas in 1952 [41]. It has been subsequently used mainly in the treatment of partial thickness burns [36, 39, 42, 43].

In the last 20 years, literature addressing the use of amnion in chronic wounds and burns has increased significantly. In order to make amnion a standard dressing alternative, safe and reliable production methods had to be implemented. To meet these needs, in several countries amnion banks have been established alongside tissue banks [44–46].

Amnion has the advantage of being thin, adhesive but not sticking, easily moldable and removable. These qualities are of great importance especially in the pediatric population. In a study performed at the Shriners Hospital for Children – Galveston, amniotic burn dressings were compared to standard ointment and gauze controls [17]. The authors reported the same wound healing rate as with the standard dressing regimen and no increase in the rate of infections or impaired long-term cosmetic results after treatment with amniotic membrane. The conclusion was that amnion can be used safely for temporary wound coverage with the chief advantage of significantly less full dressing changes and therefore improved patient comfort.

Recently, there has been a push towards a standardization and commercial availability of amniotic membranes. Commercially available amniotic membranes can now be found in fresh frozen (Grafix , Osiris Therapeutics, Inc.) and glycerol preserved form.

Xenograft

Xenografts, also known as heterografts, are used to provide a temporary wound coverage and to ensure wound homeostasis. One of the first descriptions was by Lee in 1880 [47]. A Xenograft may be obtained from various animals, although pigs are the most common donors. Typically, porcine xenograft is distributed as a reconstituted product consisting of homogenized porcine dermis which is harvested with