Skin Regeneration

This project seeks to improve survival and reduce scarring in children and adults suffering from burn and scald injuries

Skin cell image

This project seeks to improve survival and reduce scarring in children and adults suffering from burn and scald injuries. Our previous work has shown in a pre-clinical model that
skin cells can be grown on microscopic beads in the laboratory and returned to the wound bed where they form new skin and reduce scarring. We now aim to undertake a clinical evaluation of the use of cultured skin cells to treat childhood burns, which has yet to be properly assessed or quantified.

Skin colour, scar contraction and skin smoothness will be measured and compared in order to assess the effectiveness of this technique. Secondly, we will undertake a pre-clinical assessment of the efficacy of microcarriers to deliver skin cells to patients. The results from these studies will allow us to undertake the first clinical study of microcarriers in children with burn and scald injuries and compare the findings with existing treatments.

Repair of the epithelium following burn injury is usually achieved by the use of split thickness skin grafts (STSG). Limitations in donor site availability and donor site morbidity have led to the development of other techniques to replace and augment STSG.

The use of autologous keratinocytes is well established as a treatment to assist in the closure of large full thickness burns and we have obtained strong in vivo evidence that contraction is reduced by the application of sprayed cultured keratinocytes. Keratinocytes are currently sprayed onto the wound bed, delivered as a confluent sheet or delivered on a carrier membrane or sponge. Whilst each of these techniques is partially effective, each has disadvantages which result in sub-optimal, or unstable, epithelialisation and wound contraction.

The use of confluent cultured epithelial sheets has been shown to produce a friable and unstable epidermis and the use of sub-confluent suspensions of keratinocytes involves the use of damaging proteolytic enzymes, such as trypsin or dispase, to prepare the cell suspension. Furthermore, the culture of keratinocytes is costly and labour intensive and current practise requires the use of lethally irradiated mouse fibroblasts as a feeder layer to support keratinocyte growth. We are developing novel ways to grow keratinocytes without lethally irradiated mouse fibroblasts and to deliver the cells onto the wound bed.

We have recently shown that contraction of the wound is reduced when full thickness wounds are treated with a mixture of autologous keratinocytes and fibroblasts delivered on gelatin microcarriers compared with either keratinocytes sprayed in suspension or the use of very thin skin grafts. We are now working on comparing how compatible this delivery method is with a range of dermal substitutes with the aim to reduce scarring in full thickness injuries.

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