Annals of the MBC - vol. 3 - no 4 - December 1990


Dioguardi D., Brienza E., De Robertis M., Di Lonardo A.

Istituto Policattedra di Chirurgia d'Urgenza e Chirurgia Plastica, Cattedra di Chirurgia Plastica, Universita di Bari, Italia

SUMMARY. The clinical use of skin substitutes for the temporary covering of burned body surfaces has become a more frequent requirement with the increased number of burn patients who survive the acute phase and with the ever more widespread practice of early escharectomy. The various types of substitute are reviewed: biological (homologous skin, pigskin, human amniotic membrane, collagen derivatives, cultured allografts), synthetic (e.g. Duoderm, Opsite, Omiderm) and biosynthetic (e.g. Biobrane). Actual experiences with the different substitutes are described and reference is made to the use of allogenic keratinocytes as a biological dressing.

In recent years considerable importance has been given to the clinical use of skin substitutes for the temporary covering of more or less deeply damaged body surfaces.

There are two fundamental reasons for this:

  1. an increasing percentage of burn patients survive the acute phase of the burn illness and therefore must be considered for a complex programme of reconstruction;
  2. the ever' more widespread use of early escharectomy requires immediate coverage of the bloody areas.

In the absence of sufficient quantities of autologous skin, other temporary covering materials must be considered.
The constant progress in technology has now made it possible to produce numerous synthetic and biosynthetic biological substitutes capable of replacing skin, even if only partially and for very limited periods of time.
These substitutes afford the following advantages:


  • reduction of water and salt losses
  • normalization of blood protein and haematocrit levels
  • reduction of heat dispersion
  • improvement of coenaesthesia;


  • containment of bacterial load
  • cleansing of fundus by stimulation of vascularization.

The skin substitutes now available can be divided into three categories, depending on their origin and physicochemical composition:

  1. Biological skin substitutes
  2. Synthetic skin substitutes
  3. Biosynthetic skin substitutes.

Biological skin substitutes

Among the biological covering materials the following are of particular importance:

  • homologous skin
  • pigskin
  • human amniotic membrane
  • collagen derivatives
  • cultured allografts.

Homologous skin was originally used in lyophilized form (Bethesda Naval Medical School, Maryland, USA, in the 1950s) and subsequently after freezing in order to maintain viability.
Frozen skin, unlike lyophilized skin which can adhere only to the fundus of wounds, is still viable and therefore able to take and stimulate vascularization of the fundus, which is essential for the reduction of the possibility of bacterial pollution.
Frozen skin also showed itself to be less antigenic than fresh skin, and this permitted a longer-lasting take.
The concept was thus developed of a biological dressing, in view of its numerous general and local benefits for the bum patient.
The use of frozen skin however requires the creation of an expensive and complex organizational operative and legislative system (i.e. the Skin Bank), which in Italy has not met with any positive and concrete response.
As a result of these difficulties research was amplified in the field of heterological biological skin substitutes.
The most widely used sustitute of this kind was pigskin, because of its greater affinity with human skin.
Pigskin was used first fresh and then lyophilized, because it was easily preserved and immediately made available for use after immersion in physiological solution.
In recent years other preparations have been employed, among which we can mention:

  • glycerinized pigskin
  • glycerinized pigskin impregnated with silver ions
  • glycerinized pigskin conjugated with aldehydes.

Conjugation with aldehydes, in particular, makes the skin antigenically inert without any negative effect on the structural integrity of the biological material, demonstrating overall a retention 10 times as great as an untreated xenograft.
Human amniotic membrane can be considered a valid biological skin substitute because it is readily available and guarantees a good temporary covering of bum wounds without creating important immunological problems.
Amniotic membrane can be used in toto (ammos + chorion) or only as amnios (epithelium + base membrane).
According to some authors (31), ammos can be used for the covering of superficial burns, with acceleration of recovery; according to others (9), amniotic membrane is to be used in toto, with a different approach depending on the lesions to be covered:

  • amniotic face: for surface lesions, in order to favour re-epithelialization;
  • chorionic face: on deep wounds, in order to stimulate cleansing and revascularization.

Collagen derivatives

Collagen derivatives have often been used in the past in various forms: as fibrils, reconstituted strips, porous leaflets and sponges.
The various versions used have always been firmly adherent, stimulating the granulation of the covered lesions.
We can mention Dermodress (52), a cellular lamina obtained from bovine cutis by a complex process, which has shown itself to be a satisfactory long-term skin substitute.
A recent addition to biological skin substitutes has come from keratinocyte cultures.
The first experiments with cultivated skin allografts on intermediate burns dates back to 1983 (38).
With this biological dressing the lesions healed within 3 days.
It has also been observed that cultivated human skin cells reduce the capacity of HLA antigen synthesis, with the result that there are no particular complications if they are used as a biological dressing (57).
Prolonged take of these labile cultures is also promoted by the inhibiting effect exerted by freezing on the antigenic capacity of keratinocytes.

Synthetic substitutes

The most recent synthetic skin substitutes present physical features analogous to those of cutls.
Overall the ideal properties of a skin substitute are the following:

  • adherence
  • permeability to oxygen and to vapours facilitating spontaneous healing of surface lesions
  • impermeability to bacteria, which reduces the risk of contamination of the lesions
  • elasticity, which permits optimal fit to the surface to be covered
  • resistance
  • absence of toxicity
  • ease of application
  • relatively low cost.

The products most commonly used today are:

  • Duoderm (polyurethane and hydrocollolds)
  • Opsite (polyurethane film)
  • Omiderm (acrylamide film and hydroxyethylmethyerylate with polyurethane).

Biosynthetic substitutes

Biosynthetic substitutes derive from the association of biological materials such as collagen and silicone sheets.
We should remember:

  • Yannas and Burke's artificial skin (Silastle film, collagen, chondroitin sulphate)
  • Biobrane (silicone film, nylon, collagen -derived peptides).

The first of these two products is the result of a personal experience of Burke's not repeated by other researchers. It is an attempt to provide the patient with a substrate on to which a neoderm suitable for the application of a thin graft is synthesized.
Biobrane consists of a double synthetic sheet covered on both sides by peptides obtained from porcine collagen. Biobrane constitutes an outstandingly effective barrier for water vapour losses and it also has considerable capacity for adherence to the lesions, provided that haemostasis is carefully performed.

Our experience

The choice of the skin substitutes that we now use depends on the depth of the lesions.
In intermediate-superficial burns in which it is necessary to protect the lesion in order to permit rapid re-epithelialization we use synthetic sheets such as Omiderm.
The use of this acrylamide film has enabled us to achieve healing in slightly less time than in conventionally treated cases, but with the additional advantage of reducing the number of dressings.
In deep burns requiring escharectomy, biological and biosynthetic substitutes are more effective, because of their capacity of debriding the fundus of the lesions and of increasing their vascularization.
The use of these substitutes may however have surprise complications: lyophilized pigskin can cause slight sensitization, while amniotic membrane is a potential vehicle of viral infections.
To obviate these problems we have used for a number of years pigskin conjugated with aldehydes and impregnated with silver ions (E-Z Derm).
The preparation combines an antibacterial effect with a lower antigenic power and it can remain longer on escharectomized areas.
The network technique of preparation prevents accumulations of blood and pus, which enables us to carry out observations every 5-6 days.
More recently we have used Blobrane, which has shown itself to be a valid substitute in the treatment of intermediate bums and of escharectomized areas.
Biobrane has numerous perforations for the draining of fluids and the passage of disinfectants.
We have observed that Biobrane adheres for long periods, protecting the lesions from pollution and exsiccation, and at the same time preparing the fundus for permanent covering.
Lastly, there is the recent utilization of allogenic keratinocytes in association with hyperbaric oxygen in the treatment of small wounds in the limbs.
Hyperbaric oxygen therapy permits adequate preparation of the fundus of the lesions and a temporary holding of the allografts that have been cultured pending permanent covering.
The idea of using cell culture allografts for the permanent covering of seriously burned patients is very inviting. At the present time the lesser immunological reactions deriving from culture and freezing techniques allow us to use allogenic keratinocytes only as a biological dressing.

RÉSUMÉ. L'emploi clinique des substituts cutanés pour la couverture temporaire des surfaces corporelles brûlées est devenu une exigence plus fréquente avec l'augmentation du numéro des patients brûlés qui survivent à la phase aiguë et avec le recours toujours plus courant à l'escarrectomie. Les Auteurs considèrent les divers types de sostitut: biologiques (peau homologue, peau porcine, membrane amniotique humaine, dérivés du collagène, allogreffes cultivées), synthétiques (par ex. Duoderm, Opsite, Omiderm) et biosynthétiques (par ex. Biobrane). Les Auteurs décrivent leurs expériences avec les divers sostituts et ils se réfèrent en conclusion à l'emploi des kératinocytes allogéniques comme médication biologique.


  1. Dogo G.: Survival and utilization of cadaver skin. Plast. Reconstr. Surg., 10: 10, 1952.
  2. Bromberg B.E., Song I.C., Mohn M.P.: The use of pigskin as a temporary biologic dressing. Plast. Reconstr. Surg., 36: 80, 1965.
  3. Mazzolem F.: Cute liofilizzata c cute congelata nella terapia delta malattia ustione. Riv. Ital. Chir. Plast., 2: 161, 1970.
  4. Mazzoleni F., Perrone A., Saccarola L., Visentin 0., Zanella N.: Effetti delle basse temperature sulla capacitA immunogena di tessuti cutanei di ratto. Riv. Ital. Chir. Plast., 2: 97, 1970.
  5. Baxter C.R.: Homografts and heterografts as a biological dressing in the treatment of thermal injury: I st Annual Congress of the Society of German Plastic Surgery, Munich, 1970.
  6. Mazzolem F., Bortolani P.A., Rinaldi R., Winteler E.: La cute congelata come medicazione biologica negli ustionati: aspetti istologici. Riv. Ital. Chir. Plast., 3: 249, 1971.
  7. Bondoc C.C., Burke J.F.: Clinical experience with viable frozen human skin and a frozen skin bank. Ann. Surg., 174: 371, 1971.
  8. O'Donoghue M.N., Zarern H.A.: Stimulation of neurovascularization: comparative efficacy of fresh and preserved skin grafts. Plast. Reconstr. Surg., 48: 474, 1971.
  9. Robson M.C., Krizek T.J., Koss N., Samburg J.L.: Amniotic membranes as a temporary wound dressing. Surg. Gynecol. Obstet., 136: 904, 1973.
  10. Diethelm A.G., Dimik A.R., Shaw J.F., Baker H.J., Phillips S.J.: Treatment of the severely burned child with skin transplantation modified by immunosuppressive therapy. Ann. Surg., 180: 814, 1974.
  11. Burke J.F., Quinby W.C., Bondoc C.C., Cosimi A.B., Russell P.S., Szyfelbein S.K.: Immunosuppression and temporary skin transplantation in the treatment of massive third degree burns. Ann. Surg., 182: 183, 1975.
  12. Rheinwald J.G., Green H.: Formation of a keratinizing epithelium in culture by a cloned cell line derived from a teratoma. Cell., 6: 317, 1975.
  13. Schechter U Prolonged retention of glutaraldehyde-treated skin allografts and xenografts: immunological and histological studies. Ann. Surg., 182: 699, 1975.
  14. Donati L.: "La malattia da ustione". Tamburini, 1975.
  15. Amoroso L., Moschella F., Romeo L., Brisolese A.: L'impiego degh eteroinnesti nel paziente ustionato. Riv. Ital. Chir. Plast., 8: 119, 1976.
  16. Magliacani G., Rolle G., Bormioli M.: Materiali di copertura non autologa dopo escissione precoce. Riv. Ital. Chir. Plast., 8: 111, 1976.
  17. Harris N.S., Compton J.R., Abston S.: Comparison of fresh, frozen and lyophilized porcine skin and xenografts on burned patients. Burns, 2: 71, 1976.
  18. Mazzoleni F., Bortolani P.A., Chiarelli A.: Omoinnesti, eteroinnesti e sostituti cutanci artificiali nel trattamento degli ustionati. Riv. Ital. Chir. Plast., 9: 161, 1977.
  19. Ciarpella E., Baraglia M., Pantano V.: La banca della pelle: aspetti medico-legali di applicazione pratica. Riv. Ital. Chir. Plast., 9: 143, 1977.
  20. Baraglia M., Pantano V., Ciarpella G.: La banca della cute: problemi organizzativi e primi risultati. Riv. Ital. Chir. Plast., 10: 141, 1978.
  21. Donati L., Fascia M., Montorsi W., Ponzielli G., Radici G.: "Le banche dei tessuti: aspetti biologici, pratici e normativi". Minerva Medica, 1978.
  22. Magliacani G.: Trattamento chirurgico in fase acuta e materialidi copertura. Refresher course on burns, Turin, April 1978.
  23. Tavis M., Thorton J., Danet R., Barlett R.: Current status of skin substitutes. Surg. Clin. North Amer., 58: 123, 1978.
  24. Green H., Kehinde 0., Thomas J.: Growth of cultured human epidermal cells into multiple epithelia suitable for grafting. Cell Biology, 76: 565, 1979.
  25. Luterman A., Kraft E., Bookless S.: Biologic dressing: an appraisal of current practices. J.B.C.R.: 18, 1980.
  26. Tavis M., Thorton J., Barlett R., Roth J., Woodroof E.: A new composite skin prosthesis. Bums, 7: 123, 1980.
  27. Berry R.B., Hackett M.E.J.: A comparative evaluation evaluation of lyophilized homograft, lyophilized pigskin, and frozen pigskin biological dressing. Burns, 7: 84, 1980.
  28. O'Connor N.E., Mulliken J.B., Banks-Schlegel S., Kehinde 0., Green H.: Grafting of burns with cultural epithelium prepared from autologous epidermal cells. Lancet, 1: 75, 1981.
  29. Bell E., Ehrlich H.P., Sher S., Merrill C., Sarber R., Hull B., Nakatsuji T., Church D., Buttle D.J.: Development and use of living skin equivalent. Plast. Reconstr. Surg., 67: 386, 1981.
  30. Brisolese A., Romeo L., Liotta M., Caputo M., Consoli A., Micali G.: A clinical and biological evaluation of the use of xenografts. Riv. Ital. Chir. Plast., 13: 117, 1981.
  31. Vitale R., laia A., Sferrazza G., Masellis M.: Frozen amnios: a biological dressing for burn wound. Riv. Ital. Chin Plast., 13: 127, 1981.
  32. Burke J.F., Yarmas I.V., Quinby W.C., Bondoc C.C., Jung W.K.: Successful use of a physiologically acceptable artificial skin in the treatment of extensive burn injury. Ann. Surg., 194: 413, 1981.
  33. Basile A.R.D.: A comparative study of glycerinized and lyophilized porcine skin in dressings for third-degree bums. Plast. Reconstr. Surg., 69: 969, 1982.
  34. Quinby W.C., Hoover H.C., Scheflan M., Walters P.T., Slevin S.A., Bondoc C.C.: Clinical trials of amniotic membranes in burn wound care. Plast. Reconstr. Surg., 70: 711, 1982.
  35. Yarmas LV., Burke J.F., Orgill D.P., Skrabut E.M.: Wound tissue can utilize a polymeric template to synthesize a functional extension of skin. Science, 215: 174, 1982.
  36. Hermann R.P.: Organisation of a national skinbank; the use of preserved human skin with special reference to scalds in children. Atti dellIncontro Internazionale sulle ustioni, Turin, June,1982.
  37. Blondet R., Gibert-Thevenin M.A., Pierre C., Ehrsam A.: Skin preservation by programmed freezing. Br. J. Plast. Surg., 35: 530, 1982.
  38. Hefton J.M., Madden M.R., Finkelstein J.L., Shires G.T.: Grafting of the burn patient with allografts of cultured epidermal cells. Lancet, 2: 428, 1983.
  39. Stevenson R.E.: If nothing else works read the instructions: a plea for standards in skin banking. Care of the burn wound, Int. Congr. Geneva, 1983.
  40. May S.R.: Recent developments in skin banking. Care of the burn wound, Int. Congr. Geneva, 1983.
  41. Cuzzel J.: Increasing procurement of cadaveric allograft skin in the presence of limited donor sources. Care of the burn wound, Int. Congr. Geneva, 1983.
  42. Dioguardi D., Laurentaci G., Favoino B.: Residual antigenicity of lyophilized porcine skin shown in vitro by immunological methods. Care of the burn wound, Int. Congr. Geneva, 1983.
  43. May S.R.: Properties of an adherent polyurethane wound dressing: Op-site. Care of the burn wound, Int. Congr. Geneva, 1983.
  44. Woodroof E.A.: Biobrane: a new biosynthetic skin substitute.Care of the burn wound, Int. Congr. Geneva, 1983.
  45. O'Connor N.E., Gallico G.G., Compton C.C., Kehinde 0., Green H.: Grafting of burns with cultured epithelium prepared from autologous epidermal cells. Intermediate term results on three pediatric patients. In: Hunt T.K., Heppenstal K.B., Pines E., Rovee D.: "Soft and hard tissue repair: biological and clinical aspects". Vol. 2, 92, 283, Praeger Scientific, New York, 1984.
  46. Gallico G.G., O'Connor N.E., Compton C.C., Kehinde 0. Green H.: Permanent coverage of large burn wounds with autologous cultured human epithelium. New Eng. J. of Med., 311: 448, 1984.
  47. May S.R., Declement F.A.: Clinical evaluation of silverimpregnated porcine xenograft. The Bulletin and Clinical review of burn injuries, 1: 11, 1984.
  48. Hurst L.N., Brown D.H., Murray K.A.: Prolonged life and improved quality for stored skin grafts. Plast. Reconstr. Surg., 73: 105, 1984.
  49. Hermans M.H.E., Hermans R.R: Preliminary report on the use of a new hydrocolloid dressing in the treatment of burns. Burns, 11: 125, 1984.
  50. Gallico G.G., O'Connors N.E.: Cultured epithelium as a skin substitute. Clinics in Plast. Surg., 12: 149, 1985.
  51. Barrandon Y., Green IT: Cell size as a determinant of the clone-forming ability of human keratinocytes. Cell Biology, 82: 5390,1985.
  52. Sagi A., Walter P., Walter M.H., Mahler D., Ben Yakar Y., Feucht Wanger M.M.: Dermodress: a new temporary skin substitute for extensive deep bum coverage. Plast. Reconstr. Surg., 75: 223, 1985.
  53. Santi P.L., Berrino P., Galli A., Quondamcarlo C., Tanara G.: Criopreservazione della cute. Riv. Ital. Chir. Plast., 17: 43 1, 1985.
  54. Achauer B.M., Black K.S., Hewitt CW., Furnas D.W.: Immunosurgery. Clinics in Plast. Surg., 12: 293, 1985.
  55. Golan G., Eldad A., Rudenski B., Tuchman Y., Sterenberg N., Ben Hur N., Behar D., Juszynsky M.: A new temporary synthetic skin substitute. Burns, 11: 274, 1985.
  56. Towpike E., Kupiec-Weglinski J.W., Tyler D.S., Araujo J.L., Schneider T.M., Araneda D., Murphy G.M., Tilney N.L.: Cyclosporine and experimental skin allografts: long-term survival in rats treated with low maintenance doses. Plast. Reconstr. Surg., 77: 268, 1986.
  57. Faure M., Mauduit G., Demidem A., Thivolet J.: Cultured human epidermis used as allografts. Proceedings of the 35th National Congress of the Italian Society of Plastic Surgery, Milan, 1986.


Contact Us