SUMMARY. When burns are extensive the area available for donor sites is much reduced, and a point is reached when donor sites are inadequate. For this reason the cultured epidermal autograft (CEA) is very useful, although it also creates some problems, which are the subject of this paper. The problems are either technical or organizational. The technical problems include the method of debridement and the materials used for temporary wound closure. The strategies for reducing wound-bed colonization and infection are also considered. The organizational problems are related to the difficulties created by the supply of CEA. Other wound coverage techniques are also considered (Chinese autografting technique, etc.). In conclusion, it is stated that although the CEA is expensive to use and requires great care in its application, it is an irreplaceable technique that can save many lives.

When burns are extensive donor sites are limited. Escharectomy must be followed by the covering of the lesions with temporary covers, and autografts are carried out as and when donor sites are available. As the size of the burned area increases, the possible donor sites for autografting obviously decrease. And as the burn victims survive longer and longer, there comes a time when there is an inadequacy between the area of the donor sites and the need to cover the patient definitively with his/her own skin in a reasonable time limit. Traditional methods of wound closure, even with widely meshed grafts, in such cases become inadequate and in this context the only elegant and effective solution is the use of the cultured epidermal autograft (CEA), which here shows its real value. Since the first successful transplantation of the CEA in 1981, more than 400 patients have been treated in Europe and in the U.S., mainly for extensive bums.
The use of this technique not only causes problems but also poses basic questions. The problems are of two types: technical and organizational.

Some technical problems are inherent to the nature of the cultured epithelium itself, while others are purely medic o- surgical. Because of its extreme friability, the actual placement of the CEA on to an excised bed requires meticulous attention to detail.
All surgeons have received instructions as to the fragile nature of the CEA, It is classically fastened to a vaseline gauze which facilitates use. New processes of assembly on to a layer of fibrin will allow the CEA to be handled more easily in the very near future. After placement the grafted site must be kept completely immobile so that the CEA remains in place. Its fragility is most apparent in cases of infection, and the defence mechanisms of a split-thickness skin graft cannot be compared with those of the CEA. The high vulnerability of the cultured cell sheet to bacterial proteases and cytotoxins during the first weeks of maturation and attachment explains why it is more sensitive to the effects of bacteria and fungi in the wound bed. Bacterial contamination can cause nearly complete loss of the CEA, whilst a similar level of colonization will have little or no effect on the take of a meshed autograft. In an American series of cases, at the time of take-down, patients who were clinically infected had an average take of 40% versus noninfected patients who had an average take of 77%.
One of the difficulties of using CEA is therefore timing, together with the method of debridement and the materials used for temporary wound closure, on which the capacity for the CEA to become infected is partly dependent.

The answer is simple: it is widely accepted that hypoperfused and poorly oxygenated regions of a wound diminish phagocytic activity and have a much higher probability of colonization and infection. A CEA placed over chronic granulation tissue has a poor chance of successful take.
The best method for obtaining a good take, with optimal characteristics for attachment of the CEA, is early excision followed by temporay coverage with allografts which stimulate vascularization: the earlier the excision the better the CEA will take. It is desirable to perform the excision and temporary coverage within the first week, before day 10 at the latest. The quality of the homografts and their viability must not be neglected, and they constitute an important aspect. It seems more and more evident that leaving a thin layer of the homograft when it is excised significantly improves the take, as if cultured epithelium could attach and mature more rapidly on dermal connective tissue than on other types of surfaces.
For 14 allodermis patients in the Odessey series, the average take of 90% was significantly better than that obtained when engrafted homograft was removed completely from the wound-bed before application of the CEA.
The latest results suggest that if the bum woundbed is well prepared and not infected, a take rate of up to 90-95% should be expected.
If, in spite of all care in wound-bed preparation, an infection occurs, the use of topical antibiotics that are non toxic for the CEA will be justified (but only for positive surface cultures): neomycin 40 ptg + polymyxin 200 U/ml in the genitourinary irrigant proportions, or polymyxin + bacitracin + nystatin.
Another important problem is to know if CEA is appropriate for all body areas. If possible, certain areas should be avoided for different reasons: the perisphincteric regions, for obvious reasons; the axillae and joints, for reasons of mobility which would prevent the take; and the ears, owing to poor vascularization. If there are available donor sites, traditional splitthickness skin grafts will be applied to the upper extremities in an effort to provide the patient with a more resilient cover for these very important areas.
With regard to the posterior trunk and more generally decubitus areas, the use of air-fluidized beds does not hinder a good take.
Assessment of CEA take immediately after removal of the petrolatum gauze is a difficult problem since the nascent epidermis lacks a differentiated keratin layer; but this ultimately depends on 'Tamiliarization".
More worrying is the timing of the initiation of routine physical therapy. Owing to the fear of compromising graft take, patients are sometimes put under considerable sedation approaching anaesthesia. If perfect immobilization is essential for a good take, being too conservative with mobilization and rehabilitation for fear of losing the CEA is an error. The best way is to give the patients pre-operative instructions as to the fragile nature of the newly placed autografts and the importance of their cooperation during post-operative management. After surgery patients are encouraged to remain relatively immobile to prevent shearing of the grafts. The majority of authors recommend physical or occupational therapy between day 7 and day 12.
The best solution would be to stretch the durability of the grafts to their liniit with a tensile strength gauge.

The primary question is a basic one: has any individual Bum Unit enough candidates for its own CEA production? This is an essential question since it conditions the form that a "Culture Laboratory" may eventually take.
A certain number of Burn Centres have had the ambition to possess their own unit for epithelial culture production. But as the number of candidates for CEA grafting is insufficient, for financial, organizational and work-force reasons the labs are organized for research and not for production. According to need, they are then sporadically deviated from their original assignment for the benefit of the patients, when they are not in fact equipped for that purpose. The quality of the grafts shows the effects of this type of organization, and they may or may not succeed. Little by little an imbalance builds up between the aim and the real use of the lab, and as it is impossible, for financial reasons, to perform all the necessary quality controls because of understaffing with competent scientists, the lab loses its credibility and has to be closed.
Another more or less acute problem, depending on local legislations, is the difficulty for Bum Centres to obtain homografts. Although the temporary coverage of wounds by synthetic biological medications or by xenografts may not seem to be important to authors like De Luca, an emerging consensus indicates that temporary closure with allograft, following early excision, provides the best CEA take. Allograft remains the gold standard of all temporary covers and the best way of preventing infection of the wound-bed. It is therefore of primary importance to use cadaver skin, even if this means organizing regional skin banks.
Lastly, it is frequently said that post-operative management of the CEA is more complicated and timeconsuming for nurses and physicians than traditional methods of treatment. It is indeed certain that the CEA requires meticulous wound care. In our experience, this delayed discharge from the Burn Unit for our first patients, the daily time devoted to the dressings of each patient being two or three times the normal time. Then, with experience, a comprehensive nursing care plan was developed in an effort to ensure successful graft survival, with more and more simple dressings. We can say in conclusion that the problems posed, be they technical or organizational, are not insoluble.
Is price a real stumbling block? Cost effectiveness cannot be a factor in medicine when lives are saved. The problem must therefore be reassessed and the obvious questions must be of another type: is there another treatment with results that do not demonstrably differ?
Does it really increase survival? What are the real indications? As to whether there is another treatment with results that do not demonstrably differ in relation to a conventional technique, the CEA allows coverage of very extensive lesions where conventional methods would falter.
The only other possible treatment is the Shanghai graft. This Chinese technique of micrografting, in which the autografts are minced and then applied in a preprepared piece of cadaver homograft (or xenograft), is a valuable technique that has not been widely applied in the West. The in vitro seeding of a collagen gel with cultured fibroblasts, as reported by Bell, and the bilayer sheet composed of a temporary silastic overlayer and a porous collagen-chondroitin-6-sulphate matrix to act as a template for a neodermis, as developed by Burke, are two incomplete forms of coverage which need secondarily to be overgrafted by cultured epithelium.
To the question whether the CEA really increases survival, the answer is probably "yes" in cases of very extensive burns, although a prospective randomized study should be performed in order to find the real answer, which would anyway be difficult to assess because patients with large burns die from so many causes, such as pulmonary failure, cardiovascular complications and multi-organ failure.
The final point concerns the real indications. The American National Burn Information Exchange reports that a 70% TBSA full-thickness bum is associated with a mortality rate of 80%. In these conditions, and taking into consideration its high cost, the CEA should be used only in cases where traditional treatment has a poor chance of success: 65-70% TBSA full-thickness burns. Likewise, elderly patients, whose donor sites often do not heal, and very young patients, who have extremely thin skin, could be good recruits for the method. However, survival is not the only standard by which a new technique should be judged. There are many other considerations, e.g. cosmetic and functional rehabilitation, which are important end points.
To recap, the CEA is expensive to use and very sensitive to infection. It requires meticulous wound care and more professional time and effort than procedures with conventional autografts; but it still remains an irreplaceable technique which with correct use is able to save lives. Although keratinocyte cultures are a tremendous step forward for modem applied biology, as the dermis is believed to protect against secondary wound contraction and scar formation in the final wound-bed, the best alternative to autograft skin replacement would be bilayered grafts consisting of overlying epidermis attached to underlying dermis. Research has to move in this direction. Thus, wound coverage coupled with a reduced rate of sequelae could be the next step in using in vitro epidermis production.

RESUME. Quand les brûlures sont très étendues la superficie des possibles sites donneurs de peau est réduite, même insuffisante. Pour cette raison l'autogreffe épidermique cultivée (CEA en anglais) est très utile, même si elle présente certaines difficultés qui constituent le sujet de cet article. Les problèmes peuvent être de nature technique ou organisationnelle. Les problèmes techniques comprennent la méthode de débridement et les matériaux utilisés pour la couverture temporaire de la lésion. L'auteur considère en outre les stratégies pour réduire la colonisation et l'infection de la plaie. Les problèmes organisationnels concernent les difficultés créées par la provision de la CEA. Les autres techniques pour la couverture de la lésion sont prises en considération (technique chinoise d'autogreffe, etc.). En conclusion on peut dire que malgré le coût élevé de l'emploi de la CEA et la grande attention nécessaire pour son succès la CEA est une technique irremplaçable qui peut sauver beaucoup de vies.