Improved Skin Grafting Techniques
Bring Hope to Burn Patients

The skin is an important organ for regulating body temperature and general protection. It consists of the epidermis, an outer layer about 0.07mm thick, and the dermis, an inner layer measuring between 2.05 and 5mm. When the dermis is seriously burnt, it not only causes a lot of pain, but renders the wound vulnerable to bacterial invasions. Without this natural barrier, any small amount of bacteria can easily get into the bloodstream and be carried to the internal organs, and the patient may eventually die from complications.

According to a survey conducted last year, the Prince of Wales Hospital has been treating approximately 200 burn patients a year, of whom 19 per cent need surgery, and 7.7 per cent are in life-threatening conditions.

As the damaged dermis cannot restore itself, treating burns is very difficult. The usual procedure for treating burns is to graft healthy skin from other parts of the patient's body onto the wound after disinfecting the area. In patients with extensive and deep burns, donated skin, pig's skin or artificial skin is used to protect the wound temporarily, while a tiny skin sample taken from the patient is cultured in the laboratory. Using a sophisticated cell culture technique, the skin sample can be grown to 200 times its original size in three to four weeks. When the cultured skin is of adequate size -- usually at 50 to 100 times the original size -- it is ready for transplantation.

The Limitations of Cultured Skin

A patient seriously burned by
chemicals

Compared to natural skin, cultured skin is very fragile, consisting of only five to six layers of cells. Since it has no dermal layer, the wound remains susceptible to infection. Cultured skin also falls off easily if the surface of the wound is not clean. Hence, danger to the patient's life exists even after skin grafting.

At the Department of Surgery of The Chinese University of Hong Kong, Prof. Walter W.K. King, Prof. Arthur K.C. Li and Mr. P.K. Lam (now an employee of the Hospital Authority) have been conducting research on the improvement of skin culturing and grafting techniques. Their project, 'The Making and Evaluation of a Human Skin Substitute', received a grant of HK$264,000 from the University Grants Committee in 1992.

Using Collagen as Dermis and Fibrin as Adhesive

Recovering from serious burn
after skin-grafting treatment

The researchers set out to find a suitable dermis substitute. About 95 per cent of the human dermis consists of collagen, a fibrous protein that exists abundantly in the extracellular matrix, tendons and bones of animals. Since the biological structure of the ligaments of cattle is very similar to the human dermis, collagen is extracted from such ligaments as dermis substitute and processed into the form of membranes in the laboratory to provide foundation coverage for burn wounds.

Then, in their search for an adhesive, the researchers test the effects of fibrin, an insoluble protein in the blood which can help clotting. The hypothesis is that when extracted from serum, fibrin can act as a natural tissue glue which helps cultured skin adhere to the wound surface.

Nude mice were used in the experiments because they have immune deficiency and therefore cannot reject the cultured human skin. A two-square-centimetre wound was inflicted on the back of the mice which were under general anaesthetic, and four different substances or combination of substances were used to cover the wounds: (1) cultured skin; (2) cultured skin and collagen; (3) cultured skin and fibrin; (4) cultured skin, collagen, and fibrin.

In a successful skin transplant, blood vessels connect with the cultured skin in a short time, providing it with nutrients for growth. The sooner vascularization occurs, the greater the chances of recovery; while the longer the wait, the greater the chances of wound infection and rejection of the cultured skin.

In the experiments with nude mice, the first three grafting methods were shown to have produced good results, with similar success rates. When used alone with cultured skin, collagen or fibrin serves as a biocompatible bridge between the skin and the wound bed. The cultured skin proliferates to form the stratum corneum which is a biological barrier to bacteria. A combination of collagen, fibrin and cultured skin, however, seems to impose too great a diffusion barrier for the cultured skin to become vascularized. According to the experiments, therefore, cultured cells are best grafted directly onto the wound bed or in combination with either a thin layer of collagen or fibrin, but not both.

Two initial conclusions were drawn from the results. The first is that it is possible to cover the wound bed with collagen and cultured skin at the same time. Experiment has shown that this method is valid on nude mice, and suggested that a similar approach is feasible in a clinical setting. The second conclusion is that when using collagen, fibrin, and cultured skin together, it is best to do it in stages. This means that after the wound has been covered with collagen, there should be a wait of several days during which vascularization can take place, before fibrin and cultured skin are added on.

These findings coincide with the latest developments in the production of artificial skin in the United States. The US-made artificial skin consists of an outer silicon layer, which acts as a barrier against bacterial invasion, and a collagen dermis. The grafting procedure is to cover the wound with artificial skin first for a minimum of 14 to 17 days. Then the silicon layer is removed and a thin layer of the patient's own skin is grafted in its place. In early 1996, for the first time in Asia, Prof. King successfully applied this type of artificial skin to treat two adult patients with major burns at the Prince of Wales Hospital. Later when treating Pat Sin Range burn victims, he acted on the insight gained from the experiment and did the grafting in stages: covering the wound first with artificial skin and then waiting two weeks or more before transplanting the patient's own skin.

The researchers have gained a much better understanding of the characteristics of collagen and the dermis through their relentless research efforts. They will continue their work in this area with the aim of developing a type of artificial skin ideal for treating patients with serious burns.

Prof. Walter W.K. King(left) and
Mr. P.K. Lam holding a piece of
artificial skin

Prof. King graduated from the University of Wisconsin, Madison, with honours in biochemistry in 1971. He subsequently studied medicine at Vanderbilt University School of Medicine in Nashville, Tennessee and received his doctor of medicine (MD) degree in 1975. In the following years, he worked in numerous prestigious medical institutions in the United States including Massachusetts General Hospital, Harvard Medical School, Shriners Burns Institute at Boston, and Memorial Sloan-Kettering Cancer Center at New York.

Prof. King joined The Chinese University of Hong Kong as lecturer in surgery in 1984 and was promoted to senior lecturer, reader and professor in 1988, 1993 and 1995 respectively.

Prof. King's wide clinical interests include head and neck surgery, plastic and reconstructive surgery, burns surgery and endocrine surgery.

Prof. Arthur K.C. Li received his medical education at Queen's College, Cambridge University, and Middlesex Hospital Medical School, University of London. He continued his postgraduate training in England after graduation. In 1977, he won a scholarship to further his specialist training in hepatobiliary and upper gastrointestinal surgery at Harvard Medical School and Massachusetts General Hospital in Boston. Prof. Li was appointed consultant at the Royal Free Hospital in London in 1980. The following year he obtained his doctor of medicine (MD) degree from Cambridge.

Prof. Li joined The Chinese University of Hong Kong in 1982 as the founding chair of surgery. He was twice elected dean of the Medical Faculty in 1992 and 1995. In August 1996, Prof. Li assumed vice-chancellorship of The Chinese University.