A research team in £ód¼, central Poland, has found a way to make bioactive dressings that speed up wound healing and alleviate burn scars.

Despite the latest advances in treatment methods, burn scars continue to be a problem in medicine. Lumpy, tightened and overgrown skin with permanent color changes may forever remain a disfiguring memento of an accident from years ago. But the good news is that scientists are slowly learning to deal with the problem.

Researchers at the Institute of Technical Biochemistry at the £ód¼ University of Technology have invented a method for making bioactive dressings. They are produced by acetic acid bacteria of the Gluconacetobacter xylinus strain. The bacterial cellulose obtained in this way has many unique properties and can be used as a hi-tech dressing for injuries. Clinical trials carried out in Poland's largest burns treatment hospital, in the city of Siemianowice ¦l±skie in the southern region of Silesia, have shown that such cellulose dressings not only promote healing of wounds and reduce pain but also improve the appearance of the tissue which is formed under the dressing.

In most cases, burn wounds leave ugly scars because of the disorderly arrangement of collagen fibers in the wound. But under a cellulose dressing collagen fibers grow in a different manner, leading to the formation of a flat scar-one that does not overgrow and does not become lumpy. The clinical trials at the burn center have demonstrated that bacterial cellulose dressings shorten healing time by 40 percent and considerably improve the appearance of the scar.

"We are the first scientific center in Poland to conduct research on the biosynthesis of bacterial cellulose and its application," says Prof. Stanis³aw Bielecki, vice-president of the £ód¼ University of Technology and a pioneer in this field of research. "We have developed our own process to cultivate bacteria of the Gluconacetobacter xylinus strain on a specially modified substrate. We also examine the structure of cellulose produced in different cultivation conditions. Our patents, both those we have already registered and those we have applied for, protect the process of bacterial cellulose production for medical purposes. Initially, our research went in many directions. We considered the usefulness of the product for the food, textile and paper industries. Eventually, we came to the conclusion that it would be best to apply it in medicine, although we did not reject other possible applications."

Gluconacetobacter xylinus is a strain of acetic acid bacteria that do not cause disease and are human friendly. The bacterial cellulose they produce has many more advantages than plant cellulose. It is exceptionally pure, containing no hemicellulose, lignin or other substances typical of plant cellulose. This makes the production process simpler because the cellulose does not need to be purified, which is beneficial from an ecological point of view. Features that make bacterial cellulose useful for medical applications include its high elasticity-which is especially important in the case of dressings, highly crystalline structure, and superior mechanical strength. Its micro-fibrils are nearly 100 times finer than plant cellulose fibrils. Additionally, they have high water holding capacity.

Water jacket

High water content is a great advantage of dressings made of bacterial cellulose. Thanks to this property, medical staff call it hydrocellulose or "water jacket." Cellulose dressings look like a white, semi-transparent membrane with a perfectly smooth, velvety surface. The membrane resembles highly hydrated skin with more than 99 percent water content. Its thickness may range from less than a millimeter to half a centimeter. The membrane is malleable and tenacious, and almost perfectly pure biologically, with no pyrogens or protein elements that could adversely affect the wound. The perfectly smooth, mirror-like surface of the membrane prevents the dressing from binding with human tissue. Granulation tissue cells do not penetrate the cellulose structure. As a result, the dressing does not stick to the wound, is easy to change, does not cause pain and prevents secondary injuries of the tissue. The water contained in the dressing prevents the wound from drying out, while the cellulose membrane allows other substances to pass through and reach the wound through the dressing. This provides the capability to modify the dressing with medicines, such as antibiotics, bacteriostatic drugs and drugs promoting healing. Dressings of this kind have been tested by doctors at Siemianowice and by dermatologists in £ód¼ in the treatment of hard-to-heal wounds.

Sterile dressing

Microbiological cellulose synthesis enables the production of sizable dressings because bacterial cellulose can grow to large shapes. Single sheets of large sterile dressings is what doctors have dreamed of for a long time. Until recently they had no other option than to cover extensive wounds with smaller dressings placed next to one another, something that always increases the risk of infection. Burn wounds are considered to be the most serious type of wound. This is because such wounds often cover 70 to 80 percent of the patient's body. It is desirable to cover such an extensive wound area with a single dressing, and bacterial cellulose makes this possible. Another advantage of bacterial cellulose is its ability to adhere closely to all surfaces of the body, which means it is possible to properly dress areas such as the nose and ears.

"The excellent performance of bacterial cellulose in the treatment of burn wounds encouraged us to seek other medical applications for it," says Bielecki. "Further trials, this time at hospitals in £ód¼ and Gdańsk, showed that bacterial cellulose is suitable for all surgical applications, including internal ones."

Hi-tech hernia mesh

To repair hernias, surgeons now use meshes made of synthetic materials, mainly polypropylene. These implants support the operative site, but the materials they are made from still leave much to be desired, leading to infections and other problems affecting abdominal organs. Biological meshes or meshes covered with biological dressings, which form few adhesions with surrounding tissue, are also used but are extremely expensive. No less expensive is the world's only synthetic hernia mesh that fully meets surgeons' expectations. Meanwhile, the hernia mesh of bacterial cellulose made at the £ód¼ University of Technology not only equals that synthetic mesh in quality but can compete with it in price because bacterial cellulose production is increasingly cheaper and environment friendly. In vitro and in vivo tests on bacterial cellulose have confirmed that this material, owing to its biological and physical properties, is suitable for medical applications. It has been demonstrated that bacterial cellulose implanted subcutaneously (under the skin) in rats does not cause an inflammatory reaction in the surrounding tissue and becomes well absorbed in the body.

Clinical trials are also being conducted to check the suitability of bacterial cellulose as a material in the repair of severed or damaged nerves and small-diameter blood vessels. Here, bacterial cellulose comes in the form of tubes covering and protecting nerves and blood vessels. It is easier and faster for severed nerves to reconnect if wrapped up in such biocompatible "cocoons." Doctors who have used the two forms of cellulose in clinical trials have a high opinion of them. Certification and registration procedures for the dressings are well advanced and the product is likely to be brought to the market next year.

From lab to marketplace

The £ód¼ University of Technology has launched a pilot process line that is supposed to lead to the production of bacterial cellulose on an industrial scale. The production process has attracted the interest of major investors. Plans are afoot to set up a company for cellulose production based on the university's Technology Transfer Center. This would be yet another example of successful collaboration between scientists and investors.

In addition to hospitals, bacterial cellulose dressings should also be supplied to emergency services such as paramedics, firefighters and military units, doctors say. All these services should use them because the earlier the dressing is applied to the wound after the injury the more beneficial its action. It would be best to apply the dressing immediately on the scene of the accident. This is particularly important in the case of extensive burn wounds-a cellulose dressing applied to such a wound provides pain relief, cools the wound if the dressing is kept in a thermostatic container, and prevents the loss of bodily fluids. Bacterial cellulose dressings offer significant cost savings, especially in the treatment of burn wounds in the case of which patients are hospitalized repeatedly and scars take a long time to treat. Bacterial cellulose may shorten the time of treatment and even completely eliminate some of its stages.

The team working on the medical applications of bacterial cellulose is made up of researchers employed at the Institute of Technical Biochemistry at the £ód¼ University of Technology. These include Prof. Stanis³aw Bielecki, Alina Krystynowicz, Ph.D., Marek Ko³odziejczyk, Ph.D., Prof. Maria Kozio³kiewicz, and Edyta Gendaszewska-Darmach, Ph.D. Teresa Pankiewicz, M.Sc., is responsible for promoting the commercial use of the material.

Ewa Dereń