Issue Date: April 26, 2004
THE ROLLS-ROYCE OF CELLULOSES
An open bottle of a bacterial broth of Acetobacter xylinum will accumulate on its surface a slightly opaque, very wet, and remarkably sturdy film. The film is a layer of bacterial cellulose--cousin to the more famous plant cellulose found in paper.
The bacterial substance has been familiar to researchers for more than a century, although it hasn't gained much attention outside the research community. "For a long time," said Gonzalo C. (Al) Serafica, vice president of R&D at Xylos Corp., "bacterial cellulose has been a laboratory curiosity. But it has excellent properties: high water-holding capacity; multidimensional strength; and a multilayered, three-dimensional structure."
Serafica spoke at the recent American Chemical Society national meeting in Anaheim, Calif., in a symposium titled "Bacterial Cellulose: Preparation, Properties & Applications." The symposium was sponsored by the Division of Cellulose & Renewable Materials and organized by R. Malcolm Brown Jr., a professor of molecular genetics and microbiology at the University of Texas, Austin, and Tetsuo Kondo, associate professor of biomaterial science at Kyushu University, in Japan.
Most speakers at the symposium agreed that bacterial cellulose is the Rolls-Royce of celluloses. It is formed when individual bacterial cells string glucose molecules together with b-1,4 linkages and spin the polymer out in fine fibrils. The fibrils organize into flat ribbons that make up the bulk of the bacterial cellulose structure. Although chemically identical, plant cellulose has fibril bundles that are much less uniform, not as crystallized, and about 200 times thicker. Bacterial cellulose's finer fibrils mean more fibril surface area and more space between the fibrils, leading to "a remarkable capacity to hold water," according to Brown. And its regular structure makes it "one of nature's most stable materials," he said.
Bacterial cellulose has attracted a group of devoted followers who think that it should be incorporated into all sorts of products--from clothing to foodstuffs. But many commercial applications have had a hard time getting off the ground. Brown noted that bacterial cellulose has been highly underutilized because mass scale-up of bacterial cellulose production has been, to date, unsuccessful. It's due to a lack of low-cost fermentation systems, he said.
HOWEVER, Brown added, "We are having another renaissance" of interest in investigating uses for bacterial cellulose. "This year, it has really come of age." Brown and Kondo's intent in organizing the symposium was to bring together scientists who are developing unique, specialized applications for the material. These applications "exploit the unique nanostructure of cellulose," Brown said.
Take, for example, the work of Brown's graduate student, Jay Shah. Shah announced the creation of a new type of electronic paper made out of bacterial cellulose. "When you want to read something that is on the computer," Shah said, "you print it out." That is because the computer screen is backlit by fluorescent light and is harder on the eyes than reflective white paper. "Our motive was to get a display that does not depend on light behind it, but is dependent on outside lights."
Bacterial cellulose is a natural pick. It has the same reflective quality as paper and looks and feels like paper when dry. Shah incorporated electronic dyes into the cellulose and placed the sheet between transparent electrodes. The device at first looks like fine white paper. But when a voltage is applied, the dye turns dark and remains dark, even when the power is off. Low power consumption is one of the main advantages of the technology. When an opposite voltage is applied, the dye lightens and the device again appears paper-white.
Shah sees the technology as a basis for electronic books, wallpaper with changeable patterns, flexible electronic newspapers, and dynamic paper (similar to an Etch-A-Sketch screen). "The whole idea is to get an ink-on-paper look," he says. "In our case, it is dye on cellulose."
Another application is the invention of Dieter O. Klemm, a professor of chemistry and Dieter A. Schumann, a professor of surgery, both at Friedrich Schiller University in Jena, Germany. They have created an artificial blood vessel out of bacterial cellulose that they call BASYC (Bacterial Synthesized Cellulose) for use in microsurgery. Schumann described how microsurgery can repair blood vessels with diameters smaller than 3 mm and severed nerves.
Klemm and Schumann built a small platform for growing bacteria that helps the bacteria form a tube of cellulose roughly 3 mm across. "It grows like macaroni, but small," Schumann said. He and Klemm reported that BASYC works well for replacing short stretches of microvessels, at least in the animal experiments they have performed so far. They replaced parts of the carotid arteries of 40 rats and monitored the rats for over a year.
They found that bacterial cellulose does not degrade or fragment. It is mechanically hardy when wet and easily withstands handling during surgery. And it has an extremely homogeneous nanostructure, which gives it a smooth surface crucial for lining the inside of a blood vessel. Any roughness encourages formation of clots. Furthermore, they have not seen any thrombosis or indications of clotting yet. "I believe we have a very good material for coronary surgery," Schumann said, although the researchers stressed that they must now perform experiments in larger animals and in humans.
Klemm and Schumann also showed how BASYC can be used to protect a nerve fiber as it heals. One difficulty that microsurgeons encounter after performing surgery is that connective tissue inserts itself and grows between their carefully placed sutures--especially in nerves, which take a long time to heal. When Klemm and Schumann placed BASYC around the repaired nerve fiber, they found that connective tissue formed around the cellulose rather than inserting itself into the nerve sutures, giving the nerve a chance to heal.
Because it is biocompatible, bacterial cellulose lends itself to such medical uses. One of the most promising is wound care, particularly hard-to-treat wounds.
Pressure, venous, and diabetic ulcers (also known as bedsores) are tenacious wounds. They typically originate inside the body due to lack of circulation or decreased blood supply. The tissue underneath the skin dies and surfaces as a wound. These types of ulcers sometimes last for years.
Xylos, a firm with 26 employees in Langhorne, Pa., has created a wound dressing out of bacterial cellulose specifically for chronic wounds and ulcers. The company performed clinical trials on the dressing (called XCell) and is now marketing the product. The firm's Serafica described how the dressing significantly reduces wound size and promotes healing. Wounds under XCell rid themselves more quickly of dead tissue, he said, show more granulation (an indication of healing), and show faster epithelialization (skin growth). Wounds that have lasted for a year or more decrease in size or heal completely. One patient who had suffered with an ulcer for two years was healed in 12 weeks, thanks to the bacterial cellulose dressing.
Serafica pointed out that one of the unique properties of bacterial cellulose is its ability to hydrate some areas of the wound while absorbing moisture in other areas. Bacterial cellulose's high water-holding capacity, he said, allows it to contribute what is needed to different parts of the wound.
The cellulose helps remove dead tissue and promotes cleansing of the margins of the wound, Serafica said. Plus, patients found that XCell reduced pain. Serafica believes that bacterial cellulose may do this because the flexible film accommodates itself to the shape of the wound, just as skin does, and fully covers nerve endings.
A good wound dressing should be as similar to skin as possible, added Wojciech Czaja, a biochemist at the Technical University of Lodz, in Poland. Czaja and his colleagues are exploring the use of bacterial cellulose for treating another type of wound: thermal burns. For two years, the Polish group tested the effectiveness of bacterial cellulose in healing thermal burns in rats. The results were very promising, Czaja said, and so in 2001, they contacted the Center for Burn Healing in Siemianowice Slaskie, Poland.
"IT'S NOT EASY to convince physicians that you have something better than current commercial products," Czaja said, "especially when you are introducing a product produced by bacteria." But physicians at the burn center agreed to try it, and, to date, 35 patients have been treated in a clinical trial. The bacterial cellulose-treated patients lose less fluid, and they heal faster and need grafting less often. The physicians "said they have never used a better material" to treat second-degree burns, Czaja said.
"The bacterial membrane acts as an artificial skin," Czaja explained. "It even looks like skin." The slippery, transparent membrane can be cut to any shape and molds around any body part. The Polish researchers have found that bacterial cellulose is most effective at promoting healing when it is applied as soon as possible after injury. "We think that every emergency responder unit should have it on hand," Czaja said.
Before that happens, Czaja knows that there will have to be a large-scale way to produce bacterial cellulose. "We cannot say how that will happen," Czaja admitted. But "we are working on the technology." Czaja and others at the ACS symposium were convinced that "very soon--in the next few years"--it will be possible to manufacture bacterial cellulose on a grand scale.
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