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Medical Meeting Reports

American College of Surgery Clinical Congress

October 10-15, 1999


SKIN SUBSTITUTES FAIL TO MAKE THE GRADE
font=>By Karen Sandrick

Loring Rue, III, MD, of the University of Alabama, Birmingham, reported that none of the currently available options for covering burn wounds, which include biological wound coverage, allografts, and synthetic products, meets all the criteria for an ideal skin substitute.

What Is an Ideal Skin Substitute?

As described in a 1984 paper by Pruitt and Levine, a skin substitute needs to meet many specific criteria. An ideal skin substitute is non-antigeneic, nontoxic, impermeable to exogenous microorganisms, flexible, pliable, and biodegradable. It adheres to the wound, resists shear stress, and allows fibroblast ingrowth. The optimal skin substitute has enough tensile strength to resist fragmentation, an indefinite shelf life, and minimal storage requirements. It also is cost effective. Even today's gold standard for burn wound coverage--cadaver allograft--does not meet all these criteria. The supply of graft material is limited, and the quality varies widely. Cadaveric grafts bear the risk of disease transmission. Maintaining a tissue bank is expensive and subject to challenging federal regulatory requirements.

Studies of Skin Substitutes

The composite membrane substitute has two layers: a thin, outer epidermal layer of silicon rubber and an inner fine, flexible nylon fabric. The inner fabric contains porcine collagen, which promotes fibroblast ingrowth and patient acceptance. When tested as a donor site dressing and temporary wound covering, the composite membrane substitute was flexible and pliable. Its thickness could be varied to create water vapor characteristics similar to those of human skin. It also was cost effective; the cost of covering 250 cm2 of surface area was $50. However, the composite did not adhere as well as allografts, particularly in contaminated wounds, which are common in the burn patient population. It had to be removed in a timely fashion to avoid epithelialization of interstices of graft.

Cultured epithelial allografts are constructed by culturing epithelium from a 2 cm2 full thickness skin biopsy and applying fetal bone serum antibodies. Early investigations of these grafts produced exciting findings. The allografts achieved 60-80% engraftment when used to cover 50% of the wound surfaces in two children with 95% total body surface area burned (TBSAB). Engraftment was 75% in a 31-year-old man with 70% TBSAB. However, one of the largest studies of the cultured epithelial allografts by the Army Institute of Surgical Research found that allografts provided only 4.7% definitive wound coverage, and the cost of using them was $43,700 per patient.

The bilaminate artificial skin substitute that is marketed as Integra (Life Sciences Corporation) consists of a silicon outer epidermis and collagen/glycosamine-like inner dermal matrix. A randomized, multicenter trial followed 106 patients with a mean TBSAB of 47% for a period of one year after receiving the artificial skin substitute or a control material. The bilaminate skin substitute provided a median engraftment of 80% compared with 95% engraftment from initial split thickness skin grafts. Its engraftment rate was comparable to those achieved by other wound site products.

The bilaminate artificial skin substitute allowed dermal regeneration or growth and fibroblast ingrowth. It achieved water vapor transmission similar to that of human skin, and it was biodegradable. However, this type of substitute was associated with submembrane suppuration, which required split thickness grafting, and it was costly ($1,250 per 250 cm2 surface area).

The artificial skin product TransCyte is made by culturing human neonatal fibroblasts on a synthetic nylon mesh dressing. In a clinical study of ten patients with 40% TBSAB, this skin substitute was equivalent or superior to human allograft when assessed 14 days postoperatively. It was non-antigeneic, flexible, pliable, and easy to apply. Because it is transparent, use of the product allowed surgeons to examine wound healing.

TransCyte has a number of limitations, however, Dr. Rue said. The product is frozen and therefore requires preparation time before it can be applied. In addition, it also is costly at $4,050 per 250 cm2 surface area, according to one estimate.

Alloderm has a cryopreserved allogeneic dermis. Its dermal framework includes protein, such as laminin and type IV and VII collagen, which may contribute to elasticity and an improved cosmetic appearance to wound closure. According to findings from several clinical studies, the product is nonantigeneic and biodegradable. It promotes fibrovascular ingrowth; it has a long shelf life and limited storage requirements. When using this product, surgeons still have to apply thin split thickness skin grafts, however. The cost is high at $1950 per 250 cm2, Dr. Rue said.

The future directions for skin substitutes include the development of different cell types, such as cultured derived skin products, gene therapy, and chimeric grafts. A single preparation nevertheless may not achieve all the criteria for an ideal skin substitute. A hybrid product ultimately may lead the way to caring for extensive wounds in severely injured patients, Dr. Rue concluded.

Ortho Biotech

Funded through an unrestricted educational grant by Ortho Biotech.



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