A Review of a Bi-layered Living Cell Treatment (Apligraf) in the Treatment of Venous Leg Ulcers and Diabetic Foot Ulcers

Overview

Journal Clin Interv Aging

Publisher Dove Medical Press

Specialty Geriatrics

Date 2007 Nov 30

PMID 18044080

Citations 73

Authors

Larissa Zaulyanov

Robert S Kirsner

Affiliations

Soon will be listed here.

Abstract

Apligraf (Organogenesis, Canton, MA) is a bi-layered bioengineered skin substitute and was the first engineered skin US Food and Drug Administration (FDA)-approved to promote the healing of ulcers that have failed standard wound care. Constructed by culturing human foreskin-derived neonatal fibroblasts in a bovine type I collagen matrix over which human foreskin-derived neonatal epidermal keratinocytes are then cultured and allowed to stratify, Apligraf provides both cells and matrix for the nonhealing wound. Its exact mechanism of action is not known, but it is known to produce cytokines and growth factors similar to healthy human skin. Initially approved by the FDA in 1998 for the treatment of venous ulcers greater than one-month duration that have not adequately responded to conventional therapy, Apligraf later received approval in 2000 for treatment of diabetic foot ulcers of greater than three weeks duration. Herein, we review the use of Apligraf in the treatment of chronic venous leg ulcers and diabetic foot ulcers. Our goal is to provide a working understanding of appropriate patient selection and proper use of the product for any physician treating this segment of the aging population.

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References

Martin L, Kirsner R . Ulcers caused by bullous morphea treated with tissue-engineered skin. Int J Dermatol. 2003; 42(5):402-4. DOI: 10.1046/j.1365-4362.2003.01763.x. View

Streit M, Braathen L . Apligraf--a living human skin equivalent for the treatment of chronic wounds. Int J Artif Organs. 2001; 23(12):831-3. View

Falabella A, Schachner L, Valencia I, Eaglstein W . The use of tissue-engineered skin (Apligraf) to treat a newborn with epidermolysis bullosa. Arch Dermatol. 1999; 135(10):1219-22. DOI: 10.1001/archderm.135.10.1219. View

Falanga V . Tissue engineering in wound repair. Adv Skin Wound Care. 2000; 13(2 Suppl):15-9. View

Maier J, Lippitt C, Mooney E . Use of tissue-engineered skin in the dermal atrophy patient with traumatic avulsion injuries. Ann Plast Surg. 2002; 49(1):67-72; discussion 72. DOI: 10.1097/00000637-200207000-00011. View

Falanga V, Isaacs C, Paquette D, Downing G, Kouttab N, Butmarc J . Wounding of bioengineered skin: cellular and molecular aspects after injury. J Invest Dermatol. 2002; 119(3):653-60. DOI: 10.1046/j.1523-1747.2002.01865.x. View

Redekop W, Mcdonnell J, Verboom P, Lovas K, Kalo Z . The cost effectiveness of Apligraf treatment of diabetic foot ulcers. Pharmacoeconomics. 2003; 21(16):1171-83. DOI: 10.2165/00019053-200321160-00003. View

Schonfeld W, Villa K, Fastenau J, Mazonson P, Falanga V . An economic assessment of Apligraf (Graftskin) for the treatment of hard-to-heal venous leg ulcers. Wound Repair Regen. 2000; 8(4):251-7. DOI: 10.1046/j.1524-475x.2000.00251.x. View

Davis S, Martinez L, Kirsner R . The diabetic foot: the importance of biofilms and wound bed preparation. Curr Diab Rep. 2006; 6(6):439-45. DOI: 10.1007/s11892-006-0076-x. View

10.

Eaglstein W, Alvarez O, Auletta M, Leffel D, ROGERS G, Zitelli J . Acute excisional wounds treated with a tissue-engineered skin (Apligraf). Dermatol Surg. 1999; 25(3):195-201. DOI: 10.1046/j.1524-4725.1999.08186.x. View

11.

Curran M, Plosker G . Bilayered bioengineered skin substitute (Apligraf): a review of its use in the treatment of venous leg ulcers and diabetic foot ulcers. BioDrugs. 2002; 16(6):439-55. DOI: 10.2165/00063030-200216060-00005. View

12.

Falanga V, Margolis D, Alvarez O, Auletta M, Maggiacomo F, Altman M . Rapid healing of venous ulcers and lack of clinical rejection with an allogeneic cultured human skin equivalent. Human Skin Equivalent Investigators Group. Arch Dermatol. 1998; 134(3):293-300. DOI: 10.1001/archderm.134.3.293. View

13.

Mathias S, Prebil L, Boyko W, Fastenau J . Health-related quality of life in venous leg ulcer patients successfully treated with Apligraf: a pilot study. Adv Skin Wound Care. 2000; 13(2):76-8. View

14.

Hess C, Kirsner R . Orchestrating wound healing: assessing and preparing the wound bed. Adv Skin Wound Care. 2003; 16(5):246-57. DOI: 10.1097/00129334-200309000-00015. View

15.

Falabella A, Valencia I, Eaglstein W, Schachner L . Tissue-engineered skin (Apligraf) in the healing of patients with epidermolysis bullosa wounds. Arch Dermatol. 2000; 136(10):1225-30. DOI: 10.1001/archderm.136.10.1225. View

16.

Hayes Jr D, Webb G, Mandracchia V, John K . Full-thickness burn of the foot: successful treatment with Apligraf. A case report. Clin Podiatr Med Surg. 2001; 18(1):179-88. View

17.

Eaglstein W, Iriondo M, Laszlo K . A composite skin substitute (graftskin) for surgical wounds. A clinical experience. Dermatol Surg. 1995; 21(10):839-43. DOI: 10.1111/j.1524-4725.1995.tb00709.x. View

18.

Cavorsi J, Vicari F, Wirthlin D, Ennis W, Kirsner R, OConnell S . Best-practice algorithms for the use of a bilayered living cell therapy (Apligraf) in the treatment of lower-extremity ulcers. Wound Repair Regen. 2006; 14(2):102-9. DOI: 10.1111/j.1743-6109.2006.00098.x. View

19.

Waymack P, Duff R, 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(7):609-19. DOI: 10.1016/s0305-4179(00)00017-6. View

20.

Banta M, Kirsner R . Modulating diseased skin with tissue engineering: actinic purpura treated with Apligraf. Dermatol Surg. 2002; 28(12):1103-6. DOI: 10.1046/j.1524-4725.2002.02116.x. View