Centre for Biomaterials and Tissue
Engineering
Tissue engineering of skin
Skin is an important tissue engineering target for reconstructive surgery of burns victims, but increasingly also to assist in the healing of diabetes related ulcers. The latter condition is becoming increasingly prevalent with the increased rates of late onset diabetes.
Skin is the largest tissue in the body. It is a modified epithelial tissue, with a keratinised layer of dead cells that provides a physical barrier to the outside world. Epithelial tissues have sheet-like structures, making it relatively easy to overcome problems with feeding cells during growth in vitro. While a full dermal structure, shown diagramatically below, is beyond current technology, useful engineered tissues have been developed, and are in clinical use.
Above: Diagram showing the major features of mammalian skin.
The first skin substitutes developed at Sheffield were cultured epithelial autografts. These are thin sheets of keratinocytes taken by biopsy from a patient and multiplied in the laboratory. These have been used since 1981 to treat burns victims, but they suffer a number of drawbacks:
- The sheets of cells are very fragile
- Take rates typically vary between 50% and 80%
- They take 13 days to prepare, and half of the sheets have to be thrown away due to timing problems matching culturing the cells with clinical requirements
- The sheets have to be grown on a mouse fibroblast feeder layer
Above right: A photograph of a cultured epithelial autograft; this is a delicate sheet of cells floating suspended on the growth medium in the petri dish.
In the late 90's collaboration between clinical scientists and materials scientists at Sheffield made the first big improvement on this technique - the development of flexible synthetic surfaces on which keratinocytes could be easily cultured in vitro. The synthetic support medium allows rapid culture, reducing waste, and makes the tissue very much easier to handle. The cultured keratinocytes plus the synthetic support form a flexible dressing that can be applied directly to the wound bed. Clinical studies have shown that cells migrate from the dressing to the wound and greatly accelerate healing rates, frequently resulting in complete remission for chronic ulcers that had resisted other treatments.
The technology has also been successful in treating severe burns patients. The skin dressings can be delivered within nine days, offering a valuable time saving, and large areas may be covered by contiguous application of the dressings.
Above right: An electron micrograph of keratinocytes growing on a plasma polymer surface.
A second product developed at Sheffield is a replacement oral mucosa. This is a functional replacement tissue, rather than a treatment to assist wound healing. It was developed in response to a requirement in the NHS for skin for reconstructive surgery in cases such as urethral scarring.
This tissue is based on a scaffold of sterilised skin derived from skin banks. To this are added fibroblasts and keratinocytes taken from the patient during biopsy. These cells are cultured in the scaffold, giving a tough, flexible replacement tissue. The material has been used surgically by urologists, and initial results are very encouraging.
Above right: A photograph of reconstructed skin.
Researchers active in this area include:
Sheila MacNeil:
tissue engineering and clinical evaluation of skin replacement therapies
Rob Short:
surface engineering of polymers for cell growth and delivery
MyskinTM is currently being developed for market by CellTran, a University spin-out company. See their website for further details: www.celltran.co.uk