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Therapeutic Approaches - 4

Bioengineered dermal replacements

Autologous skin grafts taken using split thickness or pinch grafting have been used successfully to treat chronic wounds. They suffer from a number of disadvantages in terms of availability of donor sites, patient discomfort on creation of a second wound site and possible scarring (Valencia, 2000). Developments in the fields of biomaterials and in vitro tissue expansion has allowed development of the new discipline of bioengineering. This technology has produced a number of products intended to replace autologous skin grafts with a standardised off-the-shelf product for treatment of non-healing ulcers. Such dermal replacements are essentially comprised of a biocompatible, bioresorbable scaffold that acts as a carrier to cultured fibroblasts, keratinocytes or both. In addition to covering the wound they act as a donor of cells and growth factors to the wound site.

Two products have been evaluated in some depth for the treatment of chronic wounds. One of these, Dermagraft(TM) uses a polygalactin scaffold with cultured human neonatal fibroblasts. Whilst the cells proliferate during the manufacturing process they synthesise an extracellular matrix composed of collagen, glycosaminoglycans and fibronectin which acts as a reservoir for synthesised growth factors. It is thought to be a particularly active stimulator of angiogenesis in the recipient wound (Roberts, 2002). The efficacy of DermagraftTM treatment was compared to conventional DFU treatment in a multi-centre US study. Assessed by the endpoint of wound closure by week 12 of treatment 30% of the DermagraftTM group healed compared to 18.3% of the controls (Marston, 2003).

The second product, Appligraf(TM), is more complex in that it is a bilayered skin equivalent with dermal (fibroblast) and epidermal (keratinocyte) components. The first layer fibroblasts are cultured for 6 days on a semi-permeable membrane with bovine collagen to form a dermal matrix. This is then seeded with keratinocytes which proliferate and differentiate into an epidermal layer that is allowed to mature and form a stratum corneum (Streit, 2000). In effect the product is a viable skin construct and has been used to treat VLU and DFU with some success. Treatment of DFU produced an increase in those healed from 38 to 56% with a median reduction in healing time from 90 to 65 days. With VLU an increase from 49 to 63% healing was observed in those treated with ApligrafTM plus compression therapy compared to compression alone (Curran , 2002).

As with growth factor treatment 100% response was not seen with these therapies emphasizing the requirement for a means of identifying those patients likely to respond to treatment. This is particularly important when the relatively high cost of these products is considered.

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