Skin substitutes to enhance wound healing

Abstract

Biologically-based skin substitutes have developed as commercial products over the last 5 years. The first generation includes the collagen-based synthetic device, Integra, and Alloderm, which is based on devitalised and cross-linked human dermis. These are used as dermal replacements for third degree burns. Within the last year, the tissue-engineered product, Dermagraft-TC^®, has become available. While originally intended as a temporary covering for severe burns, Dermagraft-TC^® has proved to markedly improve the healing of deep second degree burns. The earliest living skin substitutes used autologous keratinocytes expanded in vitro. Two new products containing living cells, Dermagraft^® and Apligraf, are expected to be approved shortly for diabetic foot ulcers and venous stasis ulcers, respectively. Dermagraft^® is produced by growing human fibroblasts on a three-dimensional scaffold. The cells actively proliferate and lay down extracellular matrix to generate a papillary dermis-like device that shows a combination of angiogenic, growth factor and cell adhesion properties that enhance healing in diabetic foot ulcers. The production of Apligraf includes casting human fibroblasts in collagen, in order to generate a dermal equivalent on which is grown an epidermis. The structure is akin to a skin graft and is so applied. Despite Dermagraft^® and Apligraf being of allogeneic origin, rejection has not been an issue in clinical trials and possible contamination by pathogens has been eliminated as a concern through extensive testing. These developments represent a new concept and are expected to revolutionise wound care. They may also provide a platform for gene therapy applications.

• allogeneic
• cell adhesion
• cell migration
• dermal substitutes
• extracellular matrix
• fibroblast
• genetic modification
• growth factor
• keratinocyte
• tissue engineering
• transplantation
• wound healing