The use of cultured epithelial autograft in the treatment of major burn wounds: Eleven years of clinical experience
Introduction
The aggressive management of patients with burns of over 50%TBSA is possible due to the developing technology in intensive supportive therapy, the management of nutrition [1], and sepsis [2] providing an increased likelihood of survival. It is also widely recognised that early surgical debridement and burn wound closure improves survival [3], [4]. In addition early skin repair is also associated with scar minimisation [5]. In the treatment of major burns, it is vital to focus on ensuring that the “quality of life is worth the pain of survival” [6].
The improved potential for survival of patients with major burns originally provided the impetus to develop innovative solutions to the challenge of wound closure. Initially, xenografts were explored as wound cover but vigorous rejection of these grafts limited their usefulness [7]. Allografts, usually from cadavers, are used as biological dressings [8], [9]. Allografts, however ultimately provoke rejection through the expression of immunological crucial HLA-DR antigen by the Langerhans cells [3]. Clinicians have responded to this problem of rejection with the increased use of immunosuppressive therapies [10] but the neutropenic consequences has limited the widespread clinical application of this approach.
The need to provide skin cover in a situation of inadequate donor sites lead to the interest in laboratory based tissue expansion by culturing elements of the uninjured skin. In 1975, Reinwald and Green [11] demonstrated that disaggregated epidermal cells could be isolated and serially sub-cultured in vitro. Shortly afterwards, viable epithelial sheets, suitable for grafting were produced [12]. Epidermal cells grown in vitro did not consistently express the HLA-DR transplantation antigens [13] hence the exploration of the clinical use of cultured allografts in wound healing.
From 1981, clinical case reports describing the use of cultured keratinocytes as permanent autografts in burn wound management were published [14]. Cuono et al. [15] were the first to report that an adult survived 55%TBSA burns, of which 80% was third degree, after treatment with cadaver skin allografts and subsequently autologous keratinocyte cultures. Similarly, in case study Bettex-Galland et al. [16] reported that a 6-year old child with third degree burns to the thigh had a superior aesthetic outcome with serial sub-cultured keratinocyte sheets expanded 60:1, compared with the areas simultaneously treated with meshed split thickness skin grafts.
For burn wounds greater than 50%TBSA it is used to increase the area of cover achieved from the skin graft donor site. The traditional method of skin meshing can be used to expand the area of cover for a given size of donor site from 1:15 up 1:6 [17]. In larger burns, however, where wider mesh is necessary to facilitate larger areas of cover, there is an association with a poor scar outcome [18]. Re-cropping of the donor sites is routinely used, but is associated with an inherent delay between surgical episodes, as the donor sites require time to heal between procedures. With repeated harvesting of donor sites, the local scar morbidity increases [6] raising the question of how can laboratory based expansion techniques be used to minimise donor grafting and therefore improve clinical outcomes.
This study aims to describe the clinical experience of the introduction of CEA in treating patients with major burn injuries in Western Australia between 1992 and 2002.
Section snippets
Background
The initial treatment approach adopted in the Burn Service of Western Australia (WA) in the management of burn wounds consists of tissue salvage through expedient first aid, resuscitation and escharotomy for decompression where necessary. The aim of surgical intervention is currently to achieve debridement of the total burn eschar by 5 days post injury. The wound repair is dictated by the extent of the burn in terms of depth of injury, surface areas involved and body site of the wound.
In WA,
Demographic and clinical characteristic
The highest number of admissions for both sexes was for patients between ages 30 and 49 years. Compared to females, males were three times more likely to sustain a major burn, with three-quarters being European. Despite almost twice the population living in the metropolitan area of the State, the percentage of injuries in the rural area was only slightly less than in the metropolitan area. Flame burns were the most common causes of burn across all age groups resulting in 83% of the injuries.
Treatment provided
Discussion
When treating major burns, it is essential to expedite wound closure to prevent fluid and protein loss, exclude bacterial invasion and promote healing. Skin grafts have been used since first described in the late 1800s [20]. The problem with the use of traditional SSG in patients with burn exceeding 50%TBSA, is the adequacy of skin donor sites.
A potential solution to the problem of surface area cover is the application of laboratory based tissue expansion techniques to skin. The application of
Disclosure
CellSpray® is produced by Clinical Cell Culture Limited (C3). Fiona Wood has a financial interest in C3.
Acknowledgments
Max Bulsara, Director, Bio-statistical Consulting Group, School of Population Health, University of Western Australia, Clinical Cell Culture Limited, Perth, Western Australia, Mark Duncan-Smith, Plastic and Reconstructive Surgeon, Burn Unit Royal Perth Hospital, Multidisciplinary Burn Care Team Royal Perth Hospital and Princess Margaret Hospital. Bess Fowler, Epidemiologist, McComb Foundation and Telstra Burn Outcomes Centre.
References (29)
Quality assurance in burns patient care: the James Laing Memorial Prize Essay 1994
Burns
(1995)- et al.
Long-term skin allograft survival after short-term cyclosporin treatment in a patient with massive burns
Lancet
(1986) - et al.
Loss of HLA-DR expression by human epidermal cells after growth in culture
J Invest Dermatol
(1984) - et al.
Grafting of burns with cultured epithelium prepared from autologous epidermal cells
Lancet
(1981) - et al.
Use of cultured epidermal autografts and dermal allografts as skin replacement after burns injury
Lancet
(1986) - et al.
Current difficulties and the possible future directions in scar assessment
Burns
(1996) - et al.
Novel method of skin substitution in plastic surgery
Burns
(1989) - et al.
Use of immune-enhancing diets in burns
J Parenter Enteral Nutr
(2001) - et al.
Effects of sepsis on the VLDL kinetics: responses in basal state an during glucose infusion
Am J Physiology
(1985) - et al.
Temporary skin transplantation and immunosuppression for extensive burns
NEJM
(1974)
A comparison of conservative versus early excision therapies in severely burned patients
Ann Surg
Hypertrophic burn scars: analysis of variables
J Trauma
A conceptual history of transplantation
Homogenous Thiersch grafting as a life saving measure
Am J Surg
Cited by (159)
Conformable hyaluronic acid hydrogel delivers adipose-derived stem cells and promotes regeneration of burn injury
2020, Acta BiomaterialiaCitation Excerpt :Sheet grafts and split-thickness skin grafts can considerably reduce the mortality rate and the duration of hospitalization of patients [2]. However, several drawbacks limit the autologous skin grafting in practice, including limited donor skin, fragility, lack of smooth texture, and increased scar contractures [3]. Furthermore, severe burns can stimulate intractable systemic pathological conditions leading to infection, slow wound healing, pain, and hypertrophic scarring, which remain the major challenges for many patients.