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