Advertisement

A guide to biological skin substitutes

      This paper is only available as a PDF. To read, Please Download here.

      Summary

      The role of artificial skin substitutes in burn surgery and the treatment of chronic wounds is constantlyevolving. New products are regularly being produced and approved for clinical use. Studies on existing products clarify their efficacy and effectiveness in different clinical scenarios. This review is aimed at busy clinicians in order to bring them up to date with the latest developments in the field of artificial skin substitutes. It examines the components, struture, performance and comparative costs of the main commercial skin substitutes, and reviews briefly technologies under development that have not yet become widely available.

      Keywords

      References

        • Tompkins RG
        • Burke JF
        Alternative wound coverings.
        in: Herndon D Total Burn Care. 1st ed. W.B. Saunders Company Ltd, Philadelphia1996: 164-172
        • Pruitt Jr, BA
        • Levine NS
        Characteristics and uses of biologic dressings and skin substitutes.
        Arch Surg. 1984; 119: 312-322
        • Greenleaf G
        • Hansbrough JF
        Current trends in the use of allograft skin for patients with burns and reflections on the future of skin banking in the United States.
        J Burn Care Rehabil. 1994; 15: 428-431
        • Bravo D
        • Rigley TH
        • Gibran N
        • Strong DM
        • Newman-Gage H
        Effect of storage and preservation methods on viability in transplantable human skin allografts.
        Burns. 2000; 26: 367-378
        • Davies JW
        Synthetic materials for covering burn wounds: progress towards perfection. Part II. Longer term substitutes for skin.
        Burns Incl Therm Inj. 1983; 10: 104-108
        • Tavis MJ
        • Thornton JW
        • Bartlett RH
        • Roth JC
        • Woodroof EA
        A new composite skin prosthesis.
        Burns. 1980; 7: 123-130
        • Smith Jr, DJ
        • Robson MC
        • Meltzer T
        • Smith AA
        • McHugh TP
        • Heggers JP
        DRG-driven change in burn wound management: a success story.
        Plast Reconstr Surg. 1988; 82: 710-712
        • Purdue GF
        • Hunt JL
        • Gillespie RW
        • et al.
        Biosynthetic skin substitute versus frozen human cadaver allograft for temporary coverage of excised burn wounds.
        J Trauma. 1987; 27: 155-157
        • Hansbrough JF
        • Mozingo DW
        • Kealey GP
        • Davis M
        • Gidner A
        • Gentzkow GD
        Clinical trials of a biosynthetic temporary skin replacement, Dermagraft-transitional covering, compared with cryopreserved human cadaver skin for temporary coverage of excised burn wounds.
        J Burn Care Rehabil. 1997; 18: 43-51
        • Purdue GF
        • Hunt JL
        • Still Jr, JM
        • et al.
        A multicenter clinical trial of a biosynthetic skin replacement, Dermagraft-TC, compared with cryopreserved human cadaver skin for temporary coverageof excised burn wounds.
        J Burn Care Rehabil. 1997; 18: 52-57
        • Spielvogel RL
        A histologic study of Dermagraft-TC in patients' burn wounds.
        J Burn Care Rehabil. 1997; 18: S16-S18
        • Lukish JR
        • Eichelberger MR
        • Newman KD
        • et al.
        The use of a bioactive skin substitute decreases length of stay for pediatric burn patients.
        J Pediatr Surg. 2001; 36: 1118-1121
        • Hansbrough J
        Dermagraft-TC for partial-thickness burns: a clinical evaluation.
        J Burn Care Rehabil. 1997; 18: S25-S28
        • Noordenbos J
        • Hansbrough JF
        • Gutmacher H
        • Doré C
        • Hansbrough WB
        Enteral nutritional support and wound excision and closure do not prevent postburn hypermetabolism as measured by continuous metabolic monitoring.
        J Trauma. 2000; 49: 667-671
        • Demling RH
        • DeSanti L
        Management of partial thickness facial burns (comparison of topical antibiotics and bio-engineered skin substitutes.
        Burns. 1999; 25: 256-261
        • Morhenn VB
        • Benike CJ
        • Cox AJ
        • Charron DJ
        • Engleman EG
        Cultured human epidermal cells do not synthesize HLA-DR.
        J Invest Dermatol. 1982; 78: 32-37
        • Wikner NE
        • Huff JC
        • Norris DA
        • et al.
        Study of HLA-DR synthesis in cultured human keratinocytes.
        J Invest Dermatol. 1986; 87: 559-564
        • Nanchahal J
        • Otto WR
        • Dover R
        • Dhital SK
        Cultured composite skin grafts: biological skin equivalents permitting massive expansion.
        Lancet. 1989; 2: 191-193
        • Brain A
        • Purkis P
        • Coates P
        • Hackett M
        • Navsaria H
        • Leigh I
        Survival of cultured allogeneic keratinocytes transplanted to deep dermal bed assessed with probe specific for Y chromosome.
        BMJ. 1989; 298: 917-919
        • Phillips TJ
        • Bhawan J
        • Leigh IM
        • Baum HJ
        • Gilchrest BA
        Cultured epidermal autografts and allografts: a study of differentiation and allograft survival.
        J Am Acad Dermatol. 1990; 23: 189-198
        • Thivolet J
        • Faure M
        • Demidem A
        • Mauduit G
        Long-term survival and immunological tolerance of human epidermal allografts produced in culture.
        Transplantation. 1986; 42: 274-280
        • Zhao Y-B
        • Zhao X-F
        • Li A
        • et al.
        Clinical observations and methods for identifying the existence of cultured epidermal allografts.
        Burns. 1992; 18: 4-8
        • Eisinger M
        • Sadan S
        • Silver IA
        • Flick RB
        Growth regulation of skin cells by epidermal cell-derived factors: implications for wound healing.
        Proc Natl Acad Sci USA. 1988; 85: 1937-1941
        • Gielen V
        • Faure M
        • Mauduit G
        • Thivolet J
        Progressive replacement of human cultured epithelial allografts by recipient cells as evidenced by HLA class I antigens expression.
        Dermatologica. 1987; 175: 166-170
        • Phillips TJ
        • Gilchrest BA
        Cultured epidermal allografts as biological wound dressings.
        Prog Clin Biol Res. 1991; 365: 77-94
        • Otto WR
        • Nanchahal J
        • Lu Q-L
        • Boddy N
        • Dover R
        Survival of allogeneic cells in cultured organotypic skin grafts.
        Plast Reconstr Surg. 1995; 96: 166-176
        • Leigh IM
        • Purkis PE
        • Navsaria HA
        • Phillips TJ
        Treatment of chronic venous ulcers with sheets of cultured allogenic keratinocytes.
        Br J Dermatol. 1987; 117: 591-597
        • De Luca M
        • Albanese E
        • Bondanza S
        • et al.
        Multicentre experience in the treatment of burns with autologous and allogenic cultured epithelium, fresh or preserved in a frozen state.
        Burns. 1989; 15: 303-309
        • Rouabhia M
        • Germain L
        • Bergeron J
        • Auger FA
        Allogeneic-syngeneic cultured epithelia: a successful therapeutic option for skin regeneration.
        Transplantation. 1995; 59: 1229-1235
        • Falanga V
        • Margolis D
        • Alvarez O
        • et al.
        Rapid healing of venous ulcers and lack of clinical rejection with an allogeneic cultured human skin equivalent.
        Arch Dermatol. 1998; 134: 293-300
        • Sabolinski ML
        • Alvarez O
        • Auletta M
        • Mulder G
        • Parenteau NL
        Cultured skin as a ‘smart material’ for healing wounds: experience in venous ulcers.
        Biomaterials. 1996; 17: 311-320
        • Eaglstein WH
        • Iriondo M
        • Laszlo K
        A composite skin substitute (graftskin) for surgical wounds. A clinical experience.
        Dermatol Surg. 1995; 21: 839-843
        • Falanga VJ
        Tissue engineering in wound repair.
        Adv Skin Wound Care. 2000; 13 (2 Suppl.): 15-19
        • Waymack P
        • Duff RG
        • Sabolinski M
        The effect of a tissue engineered bilayered living skin analog, over meshed split-thickness autografts on the healing of excised burn wounds.
        The Apligraf Burn Study Group. Burns. 2000; 26: 609-619
        • Hansbrough JF
        • Cooper ML
        • Cohen R
        • et al.
        Evaluation of a biodegradable matrix containing cultured human fibroblasts as a dermal replacement beneath meshed skin grafts on athymic mice.
        Surgery. 1992; 111: 438-446
        • Hansbrough JF
        • Morgan J
        • Greenleaf G
        • Underwood J
        Development of a temporary living skin replacement composed of human neonatal fibroblasts cultured in Biobrane, a synthetic dressing material.
        Surgery. 1994; 115: 633-644
        • Cooper ML
        • Hansbrough JF
        • Spielvogel RL
        • Cohen R
        • Bartel RL
        • Naughton G
        In vivo optimization of a living dermal substitute employing cultured human fibroblasts on a biodegradable polyglycolic acid or polyglactin mesh.
        Biomaterials. 1991; 12: 243-248
        • Naughton G
        • Mansbridge J
        • Gentzkow G
        A metabolically active human dermal replacement for the treatment of diabetic foot ulcers.
        Artif Organs. 1997; 21: 1203-1210
        • Allenet B
        • Paree F
        • Lebrun T
        • et al.
        Cost-effectiveness modeling of Dermagraft for the treatment of diabetic foot ulcers in the French context.
        Diabetes Metab. 2000; 26: 125-132
        • Hansbrough JF
        • Doré C
        • Hansbrough WB
        Clinical trials of a living dermal tissue replacement placed beneath meshed, split-thickness skin grafts on excised burn wounds.
        J Burn Care Rehabil. 1992; 13: 519-529
        • Wainwright D
        • Madden M
        • Luterman A
        • et al.
        Clinical evaluation of an acellular allograft dermal matrix in full-thickness burns.
        J Burn Care Rehabil. 1996; 17: 124-136
        • Lattari V
        • Jones LM
        • Varcelotti JR
        • Latenser BA
        • Sherman HF
        • Barrette RR
        The use of a permanent dermal allograft in fullthickness burns of the hand and foot: a report of three cases.
        J Burn Care Rehabil. 1997; 18: 147-155
        • Yannas IV
        • Burke JF
        Design of an artificial skin. I. Basic design principles.
        J Biomed Mater Res. 1980; 14: 65-81
        • Yannas IV
        • Burke JF
        • Gordon PL
        • Huang C
        • Rubenstein RH
        Design of an artificial skin. II. Control of chemical composition.
        J Biomed Mater Res. 1980; 14: 107-131
        • Burke JF
        • Yannas IV
        • Quinby Jr, WC
        • Bondoc CC
        • Jung WK
        Successful use of a physiologically acceptable artificial skin in the treatment of extensive burn injury.
        Ann Surg. 1981; 194: 413-428
        • Heimbach D
        • Luterman A
        • Burke J
        • et al.
        Artificial dermis for major burns: a multi-center randomized clinical trial.
        Ann Surg. 1988; 208: 313-320
        • Sheridan RL
        • Hegarty M
        • Tompkins RG
        • Burke JF
        Artificial skin in massive burns — results to ten years.
        Eur J Plast Surg. 1994; 17: 91-93
        • Stern R
        • McPherson M
        • Longaker MT
        Histologic study of artificial skin used in the treatment of full-thickness thermal injury.
        J Burn Care Rehabil. 1990; 11: 7-13
        • Orgill DP
        • Butler C
        • Regan JF
        • Barlow MS
        • Yannas IV
        • Compton CC
        Vascularized collagen-glycosaminoglycan matrix provides a dermal substrate and improves take of cultured epithelial autografts.
        Plast Reconstr Surg. 1998; 102: 423-429
        • Pandya AN
        • Woodward B
        • Parkhouse N
        The use of cultured autologous keratinocytes with Integra in the resurfacing of acute burns.
        Plast Reconstr Surg. 1998; 102: 825-828
        • Grzesiak JJ
        • Pierschbacher MD
        • Amodeo MF
        • Malaney TI
        • Glass JR
        Enhancement of cell interactions with collagen/glycosaminoglycan matrices by RGD derivatization.
        Biomaterials. 1997; 18: 1625-1632
        • Matsuda K
        • Suzuki S
        • Isshiki N
        • et al.
        A bilayer ‘artificial skin’ capable of sustained release of an antibiotic.
        Br J Plast Surg. 1991; 44: 142-146
        • Yannas IV
        • Lee E
        • Orgill DP
        • Skrabut EM
        • Murphy GF
        Synthesis and characterization of a model extracellular matrix that induces partial regeneration of adult mammalian skin.
        Proc Natl Acad Sci USA. 1989; 86: 933-937
        • Rheinwald JG
        • Green H
        Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells.
        Cell. 1975; 6: 331-344
        • Green H
        • Kehinde O
        • Thomas J
        Growth of cultured human epidermal cells into multiple epithelia suitable for grafting.
        Proc Natl Acad Sci USA. 1979; 76: 5665-5668
        • Gallico III, GG
        • O'Connor NE
        • Compton CC
        • Kehinde O
        • Green H
        Permanent coverage of large burn wounds with autologous cultured human epithelium.
        N Engl J Med. 1984; 311: 448-451
        • Carsin H
        • Ainaud P
        • Le Bever H
        • et al.
        Cultured epithelial autografts in extensive burn coverage of severely traumatized patients: a five year single-center experience with 30 patients.
        Burns. 2000; 26: 379-387
        • Gallico III, GG
        • O'Connor NE
        • Compton CC
        • Remensnyder JP
        • Kehinde O
        • Green H
        Cultured epithelial autografts for giant congenital nevi.
        Plast Reconstr Surg. 1989; 84: 1-9
        • Carter DM
        • Lin AN
        • Varghese MC
        • Caldwell D
        • Pratt LA
        • Eisinger M
        Treatment of junctional epidermolysis bullosa with epidermal autografts.
        J Am Acad Dermatol. 1987; 17: 246-250
        • Morykwas MJ
        • Beason ES
        • Argenta LC
        Scalp necrosis in a neonate treated with cultured autologous keratinocytes.
        Plast Reconstr Surg. 1991; 87: 549-552
        • Compton CC
        • Hickerson W
        • Nadire K
        • Press W
        Acceleration of skin regeneration from cultured epithelial autografts by transplantation to homograft dermis.
        J Burn Care Rehabil. 1993; 14: 653-662
        • Kangesu T
        • Navsaria HA
        • Manek S
        • et al.
        A porcine model using skin graft chambers for studies on cultured keratinocytes.
        Br J Plast Surg. 1993; 46: 393-400
        • Navsaria HA
        • Kangesu T
        • Manek S
        • Green CJ
        • Leigh IM
        An animal model to study the significance of dermis for grafting cultured keratinocytes on full thickness wounds.
        Burns. 1994; 20: S57-S60
        • Nave M
        Wound bed preparation: approaches to replacement of dermis.
        J Burn Care Rehabil. 1992; 13: 147-153
        • Odessey R
        Addendum: multicenter experience with cultured epidermal autograft for treatment of burns.
        J Burn Care Rehabil. 1992; 13: 174-180
        • Siwy BK
        • Compton CC
        Cultured epidermis: Indiana University Medical Center's experience.
        J Burn Care Rehabil. 1992; 13: 130-137
        • Hafemann B
        • Hettich R
        • Ensslen S
        • et al.
        Treatment of skin defects using suspensions of in vitro cultured keratinocytes.
        Burns. 1994; 20: 168-172
        • Woodley DT
        • Peterson HD
        • Herzog SR
        • et al.
        Burn wounds resurfaced by cultured epidermal autografts show abnormal reconstitution of anchoring fibrils.
        JAMA. 1988; 259: 2566-2571
        • Compton CC
        • Gill JM
        • Bradford DA
        • Regauer S
        • Gallico GG
        • O'Connor NE
        Skin regenerated from cultured epithelial autografts on full-thickness burn wounds from 6 days to 5 years after grafting. A light, electronmicroscopic and immunohistochemical study.
        Lab Invest. 1989; 60: 600-612
        • Franzi AT
        • D'Anna F
        • Zicca A
        • Trabucchi E
        Histological evaluation of human cultured epithelium before and after grafting.
        Burns. 1992; 18: S26-S31
        • Ng RL
        • Woodward B
        • Bevan S
        • Green C
        • Martin R
        Retroviral marking identifies grafted autologous keratinocytes in porcine wounds receiving cultured epithelium.
        J Invest Dermatol. 1997; 108: 457-462
        • Hunyadi J
        • Farkas B
        • Bertényi C
        • Oláh J
        • Dobozy A
        Keratinocyte grafting: a new means of transplantation for full-thickness wounds.
        J Dermatol Surg Oncol. 1988; 14: 75-78
        • Kaiser HW
        • Stark GB
        • Kopp J
        • Balcerkiewicz A
        • Spilker G
        • Kreysel HW
        Cultured autologous keratinocytes in fibrin glue suspension, exclusively and combined with STS-allograft (preliminary clinical and histologicalreport of a new technique).
        Burns. 1994; 20: 23-29
        • Ronfard V
        • Broly H
        • Mitchell V
        • et al.
        Use of human keratinocytes cultured on fibrin glue in the treatment of burn wounds.
        Burns. 1991; 17: 181-184
        • Ronfard V
        • Rives JM
        • Neveux Y
        • Carsin H
        • Barrandon Y
        Long-term regeneration of human epidermis on third degree burns transplanted with autologous cultured epithelium grown on a fibrin matrix.
        Transplantation. 2000; 70: 1588-1598
        • Grant I
        • Warwick K
        • Marshall J
        • Green C
        • Martin R
        The coapplication of sprayed cultured autologous keratinocytes and autologous fibrin sealant in a porcine wound model.
        Br J Plast Surg. 2002; 55: 219-227
        • Lam PK
        • Chan ESY
        • To EWH
        • Lau CH
        • Yen SC
        • King WWK
        Development and evaluation of a new composite Laserskin graft.
        J Trauma. 1999; 47: 918-922
        • Andreassi L
        • Pianigiani E
        • Andreassi A
        • Taddeucci P
        • Biagioli M
        A new model of epidermal culture for the surgical treatment of vitiligo.
        Int J Dermatol. 1998; 37: 595-598
        • Chan ESY
        • Lam PK
        • Liew CT
        • Lau HCH
        • Yen RSC
        • King WWK
        A new technique to resurface wounds with composite biocompatible epidermal graft and artificial skin.
        J Trauma. 2001; 50: 358-362
        • Navarro FA
        • Stoner ML
        • Park CS
        • et al.
        Sprayed keratinocyte suspensions accelerate epidermal coverage in a porcine microwound model.
        J Burn Care Rehabil. 2000; 21: 513-518
        • König A
        • Bruckner-Tuderman L
        Epithelial-mesenchymal interactions enhance expression of collagen VII in vitro.
        J Invest Dermatol. 1991; 96: 803-808
        • Ghosh MM
        • Boyce S
        • Layton C
        • Freedlander E
        • MacNeil S
        A comparison of methodologies for the preparation of human epidermal-dermal composites.
        Ann Plast Surg. 1997; 39: 390-404
        • Chakrabarty KH
        • Dawson RA
        • Harris P
        • et al.
        Development of autologous human dermal-epidermal composites based on sterilized human allodermis for clinical use.
        Br J Dermatol. 1999; 141: 811-823
        • Boyce ST
        • Hansbrough JF
        Biologic attachment, growth, and differentiation of cultured human epidermal keratinocytes on a graftable collagen and chondroitin-6-sulfate substrate.
        Surgery. 1988; 103: 421-431
        • Hansbrough JF
        • Boyce ST
        • Cooper ML
        • Foreman TJ
        Burn wound closure with cultured autologous keratinocytes and fibroblasts attached to a collagen-glycosaminoglycan substrate.
        JAMA. 1989; 262: 2125-2130
        • Boyce ST
        Skin substitutes from cultured cells and collagen-GAG polymers.
        Med Biol Eng Comput. 1998; 36: 791-800
        • Boyce ST
        • Kagan RJ
        • Meyer NA
        • Yakuboff KP
        • Warden GD
        The 1999 clinical research award. Cultured skin substitutes combined with Integra artificial skin to replace native skin autograft and allograft for the closure of excised full-thickness burns.
        J Burn Care Rehabil. 1999; 20: 453-461