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Volume 2 • Number 6 • 1997
Contents: (Full text available in print edition.)
Human Skin Equivalent (HSE) Apligraf®
Part II Clinical Use
Preparation of the wound bed, proper application of Apligraf, and patient compliance with underlying therapy for underlying disease are probably the most important determinants of clinical efficacy.1,2

What are the most important things to remember about preparing the wound?1

1. Debride the wound bed so that it is as clean and free of fibrotic/necrotic tissue as possible.
2. After debridement, cleanse the wound bed of debris by irrigating with a sterile, non-cytotoxic saline solution. You may apply gentle pressure to stop bleeding and/or use topical hemostatic agents prior to application.
3. Contain bacterial infection.
4. Control leg edema and heavy wound exudation with elevation and compression of the leg.
5. Implement appropriate therapies for underlying venous insufficiency.

Should antimicrobial agents be used prior to the procedure?

The commensals in venous leg ulcers are generally not associated with the kind of frank infection that would preclude the application of HSE. If necessary, oral, topical or injectable antimicrobial agents may be used for one week prior to application.1,2 Several commonly used burn wound antimicrobial agents (including mafenide acetate, polymyxin B sulfate, nystatin and sodium hypochlorite) may have a deleterious effect on HSE. Certain cytotoxic agents (Dakin's solution, mafenide acetate, Scarlet Red dressing, tincoban, zinc sulfate, povidone iodine solution and chlorhexidine) can destroy cellular components of skin and HSE, and following their use, the wound should be thoroughly cleansed with physiological saline before application.1

Use of Apligraf1

1. Apligraf is intended for single-use only. It should be kept on its tray on the medium in an incubator (19-31°C) until ready for use. It remains viable for up to five days from the moment it is sealed in the pouch.
2. Before opening the plastic container, check the pH of the mediumby comparing the colour to the colours on the chart provided. The medium is compromised if the colour is purple, and possibly contaminated if the colour is yellow.
3. Handle the Apligraf as little as possible, and use sterile technique.
4. Do not allow the HSE to dry out after opening the package, and place it on the wound bed within 30 minutes.
5. The dermal layer (the glossy layer closest to the medium in the container) should be placed flush with the wound surface. The epidermal layer (matte, dull finish) should be facing up, exposed to the air. Express any trapped air.1 HSE must be trimmed to fit inside the edge of the ulcer margins.
6. If exudateis a problem, slits (pie-crusting) with a scalpel blade, punch biopsies or shredding may help prevent the HSE from floating off the surface of the wound. To prevent contamination, the holes should be made after HSE has been removed from the media well.2
7. It is very important to immobilize the HSE in contact with the wound bed. If securing of the HSE is not complete, staples, sutures or other methods should be used to prevent shear or friction.2 For venous leg ulcers, cover the HSE with a nonadherent primary dressing (e.g. Tegapore® or Mepitel®), then apply a pressure bolster (rolled or folded gauze or a foam plug) and cover the bolster with an elastic wrap/compression bandage.1
8. Within one week of application, HSE may appear translucent and cellophane-like. The graft may degrade partially or completely following the initial application. Degraded HSE may appear yellow and gelatinous, and its similarity to purulent exudate may lead to inappropriate diagnosis of skin infection. In acute or fresh wounds, HSE appears pinkish or whitish-opaque within 1-2 weeks.1
9. In most cases, one to two applications of HSE will be sufficient; in a minority of patients, three applications may be necessary. Reapply within six to eight weeks if less than 50% of the original wound area has closed, or if the HSE has not completely adhered to the wound. Do not disrupt healing tissue or adherent HSE, but gently remove nonadherent remnants of the product.1
In a number of patients, a single application of HSE has converted chronic or non-healing wounds to acute, more responsive wounds. Following the initial application, it may be advisable to wait 8-12 weeks before using a second HSE in order to determine whether or not wound healing has been jump-started and to prevent unnecessary expense.3
Dr Gary Sibbald, Toronto
10. The primary dressing covering the HSE should be inspected and changed at least once a week. Highly exudative wounds may require more frequent changes.1

Information for Patients

Patients should be told to expect some scarring but, generally a return of skin colour and a good cosmetic outcome.4

Venous leg ulcer patients should elevate their feet as much as possible for the first week after application and the underlying venous disease managed aggressively to prevent recurrence. After the ulcer has healed, they should wear elastic compression stockings delivering 30-40 mm Hg of pressure and have follow-up inspections every three months for one year. It is also important that they maintain proper nutrition.1

One of the most exciting benefits of HSE therapy is its ability to dramatically accelerate wound closure, up to two to three times faster than conventional multilayer compression therapy. In the pivotal leg ulcer study, HSE closed as many wounds by eight weeks as conventional therapy did by six months and also resulted in a significantly greater number of patients with 100% wound closure. These differences were even more striking with particulary difficult to heal ulcers (larger or of longer duration).

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  1. Data on file, Novartis Pharma AG.
  2. Falanga V, Margolis D, Alvarez O et al. Rapid healing of venous ulcers and lack of rejection with an allogeneic cultured Human Skin Equivalent. Submitted for publication.
  3. Sibbald G. Personal communication. July, 1997.
  4. Sabolinski ML, Alvarez O, Auletta M et al. Cultured skin as a 'smart material' for healing wounds: experience in venous ulcers. Biomaterials1996; 17: 311-320.

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Update on Drugs
Class Name/Company Approval Dates and Comments
Anti-acne & antipsoriatic Tazarotene Gel
0.05%, 0.1%

Tazorac® topical gel
Approved by the FDA June 13, 1997 for the topical treatment of patients with stable plaque psoriasis of up to 20% body involvement, or facial acne vulgaris of mild to moderate severity. Previously approved in Germany and Canada. (Reviewed in Volume 2, Number 4, Pages 1-2.)
Class Name/Company Drug Warning
Anti-HIV Indinavir
Prescribing information is to be updated, US and worldwide, to include warnings about the possibility of patients developing hemolytic anemia. According to Merck, 20 cases have been reported in 140,000 patients and no causal link has been established, but this warning is appropriate as the condition needs to be recognized and treated quickly.

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EDITOR: Stuart Maddin Associate Editor: David I. McLean INTERNET EDITOR: Harvey Lui PRINCIPAL MEDICAL WRITER: Susan Kingsley Manuscript Editor: Rodger Hall Editorial Advisory Board: Kenneth A. Arndt, Beth Israel Hospital & Harvard Medical School, Boston; Wilma Fowler Bergfeld, Cleveland Clinic, Cleveland; Jan D. Bos, University of Amsterdam, Amsterdam; Enno Christophers, Universitäts-Hautklinik, Kiel; Hugo Degreef, Catholic University, Leuven; Richard L. Dobson, Medical University of South Carolina, Charleston; Boni E. Elewski, Case Western Reserve University, Cleveland; Barbara A. Gilchrest, Boston University School of Medicine, Boston; W. Andrew D. Griffiths, St. Johns Institute of Dermatology, London; Vincent C.Y. Ho, University of British Columbia, Vancouver; James J. Leyden, University of Pennsylvania, Philadelphia; Howard I. Maibach, University of California Hospital, San Francisco; Larry E. Millikan, Tulane University Medical Center, Louisiana; Takeji Nishikawa, Keio University School of Medicine, Tokyo; Constantin E. Orfanos, Freie Universitäts Berlin, Universitätsklinikum Benjamin Franklin, Berlin; Stephen L. Sacks, Viridae Clinic Sciences, Vancouver; Alan R. Shalita, SUNY Health Sciences Center, Brooklyn; Stephen K. Tyring, University of Texas Medical Branch, Galveston; John Voorhees, University of Michigan, Ann Arbor; Klaus Wolff, University of Vienna, Vienna
Skin Therapy Letter®. (ISSN 1201-5989) Copyright 1997 by International Skin Therapy Newsletter Inc. All rights reserved. Reproduction in whole or in part by any process in whole or in part is strictly forbidden without prior consent of the publisher in writing.
Published six times yearly by International Skin Therapy Newsletter Inc., 835 West Tenth Avenue, Vancouver, British Columbia, Canada V5Z 4E8. Tel: (604) 874-6112. Fax: (604) 873-9919. Annual subscription: Canadian $85 individual; $155 institutional (GST included). US $60 individual; $110 institutional. Outside North America: US$80 individual; $130 institutional. Quotes on multiple subscriptions and student rates supplied upon request.
Skin Therapy Letter Editor: Dr. Stuart Maddin Vol. 2 No. 6
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