Skin Substitutes in Burns
Introduction
The natural history of burn injury has been substantially modified over the past few decades. The first recorded recognition of the exaggerated fluid requirements of burn patients was probably that of Underhill in 1930[1]. After this important clinical observation, investigations began to develop methods to manage burn shock. In the aftermath of the Coconut Grove fire, Moore and colleagues[2]refined the concept of burn resuscitation and proposed a formula for intravenous volume repletion based on body weight[3], and in the 1950’s the Evans formula was promulgated by the staff at the United States Army Institute of Surgical Research[4]. Subsequent refinements in burn shock resuscitation have virtually eliminated this as a cause of death. In the 1970’s, the advantage of early excision and closure of small burn wounds was recognized[5]. This excisional approach was subsequently taken to patients with large injuries by Burke and others6, 7, 8who documented truncated hospital stays and enhanced survival in burn patients who were routinely expected to die; a burn over more than a third of the body surface being almost universally lethal at that time.
Refinement of the surgical approaches to large wounds combined with the ongoing evolution of critical care techniques has extended our ability to support patients with increasingly severe injuries through the physiologic trial of staged wound closure. Burn physical and occupational therapy and burn reconstruction have developed in parallel, facilitating our ability to deliver increasingly satisfying long term outcomes. However, further progress is seriously impaired by our lack of a suitable skin substitute. In both the acutely injured and those requiring extensive post burn reconstruction, the absence of a durable skin substitute regularly hinders recovery. The successful development of a permanent skin substitute will have an enormous impact on the care of patients with serious burns.
Skin is a complex organ. Functionally, it has two layers with a highly specialized and effective bonding mechanism. The epidermis, consisting of the strata basale, spinosum, granulosum and corneum, provides a vapor and bacterial barrier. The dermis provides strength and elasticity. The thin epidermal layer is constantly replacing itself from its basal layer, with new keratinocytes undergoing terminal differentiation over approximately 4 weeks to anuclear keratin filled cells that make up the stratum corneum, which provides much of the barrier function of the epidermis. The basal layer of the epidermis is firmly attached to the dermis by a complex bonding mechanism containing collagen types IV and VII. When this bond fails, serious morbidity results, as demonstrated by the disease processes of toxic epidermal necrolysis[9]and dystrophic epidermolysis bullosa[10].
At present, most full thickness burn wounds are best closed as quickly as possible with split thickness autograft. However, split thickness autograft is an imperfect replacement for full thickness skin, may be limited in quantity and is associated with donor site morbidity. The ideal skin substitute (Table 1): (1) is inexpensive, (2) has a long shelf life, (3) is used off the shelf, (4) is non-antigenic, (5) is durable, (6) is flexible, (7) prevents water loss, (8) is a barrier to bacteria, (9) conforms to irregular wound surfaces, (10) is easy to secure, (11) grows with children, (12) is applied in one operation, (13) does not become hypertrophic and (14) does not exist at the present time11, 12.
Conceptually, skin substitutes are temporary or permanent; epidermal, dermal or composite; and biologic or synthetic. Biologic components are xenogeneic, allogenic or autogenic. There is a research effort centered on many of the possible permutations of these traits. From a practical perspective, the current reality is that skin substitutes are designed to be temporary or permanent. This manuscript will attempt to review the uses and formulations of temporary and permanent substitutes now available and will speculate on future directions in skin substitute research. Whenever possible, proprietary product names will not be used; any products not mentioned are not purposefully excluded.
Section snippets
Current temporary substitutes
Temporary skin substitutes provide transient physiologic wound closure. Physiologic wound closure implies a degree of protection from mechanical trauma, vapor transmission characteristics similar to skin and a physical barrier to bacteria. These membranes therefore contribute to the creation of a moist wound environment with a low bacterial density. There are four common uses for temporary skin substitutes: (1) as a dressing on donor sites to facilitate pain control and epithelialization from
Current permanent skin substitutes
A useful permanent skin substitute remains the `holy grail' of burn research. Although no ideal substitute exists at present, there are a number of devices currently available that contribute to permanent coverage of burn wounds that will be discussed here.
Future directions
There are two particularly important areas in which significant change may occur in this field over the next few years: the development of temporary dressings containing growth factor secreting allogenic tissues that stimulate native wound healing and the realization of a permanent composite skin replacement. Other areas in which progress is likely to be seen include improvements in temporary skin substitutes and refinements in skin banking techniques.
Viral transfection techniques have evolved
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