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Imagine marshaling tiny bacteria to weave a new kidney. Or to repair joints. Or even to replace parts of an injured skull. Paul Gatenholm and Rafael Davalos, engineers at the Virginia Tech-Wake Forest University School of Biomedical Engineering (Blacksburg, VA, Winston-Salem, NC), have developed a process for controlling the motion of cellulose-producing Acetobacter xylinum bacteria, guiding them to produce structures that the researchers hope will one day be able to support cartilage, bone tissue, and other biomaterials.
While at Chalmers University of Technology (Göteborg, Sweden), Gatenholm learned how to control bacteria to create collagen-like fiber layers that can conform to a template. However, the bacteria’s mechanical properties could not be controlled beyond thin, flexible layers because cellulose scaffolds produced using Acetobacter xylinum bacteria lacked the stiffness required to support healing bone or cartilage. Working on the same problem across the ocean, Davalos found a solution for controlling bacterial motion to form sound structures: electrical fields.
With support from Virginia Tech’s Institute for Critical Technology and Applied Science, the two researchers teamed up to experiment with the use of electrical fields to control the movement of cellulose-producing bacteria. As a result, they were able to induce the bacteria to move back and forth like a loom, transforming cellulose layers into 3-D architectures. “The invention of controlling the motion of bacteria and the alignment of nanofibrils provides a way to control bacteria’s mechanical properties in two dimensions,” Gatenholm remarks. “Bacteria produce layer upon layer of fibers, and these grow into 3-D structures.”
By controlling bacterial motion, it is possible to engineer the needed mechanical properties to support microscale fluid flow and the environment for the target cells to attach and grow, Gatenholm says. “Nanofibril alignment such as in natural collagen tissue will greatly improve the strength and stiffness of scaffolds.”
In addition to the challenge of controlling bacterial motion, the researchers faced another obstacle: porosity. With a water content of approximately 99%, bacterial cellulose is soft and flexible. However, its lack of porosity prevents natural cell growth. To surmount this obstacle, Gatenholm hit on the idea of using wax. “Wax particles of different sizes are placed in a fermentation broth and lightly fused,” explains Gatenholm. “Bacteria go around the particles and spin a network around them. The particles are then melted out, bacteria are removed, and we have a nice open space with interconnectivity, so the cells that we want to use for building tissue—chondrocytes, osteoblats, fibroblasts, smooth muscle cells—can be attracted.”
Having learned how to control the motion of bacterial cellulose and how to ensure an environment conducive to cell growth, the Virginia Tech engineers see their findings as the key to future healing biomaterials. The material is already commercially available from Xylos Corp. (Langhorne, PA) as a wound dressing, and, based on his research at Chalmers University, Gatenholm has founded several startups to develop the technology. One of them, Arterion (Göteborg, Sweden), models artificial blood vessels from the Acetobacter xylinum microbe to revascularize patients whose diseased blood vessels have an internal diameter of less than 5 mm. New vessels are formed by surrounding a template with the bacteria. “Acetobacter xylinum needs oxygen,” says Gatenholm. “If you place a rubber glove into a fermentation broth and add oxygen into the glove, the bacteria will come to surface of glove and cover it, making a copy of it.”
Down the road, Gatenholm foresees many applications for his hard-working bacterial weavers. In addition to small blood vessels, cartilage, and bone, bacterial cellulose is being evaluated by several research groups as implants and possible scaffolds for tissue engineering. “Neural regeneration, skin, bladders, kidneys—there are many organs that need replacement.” In addition, Virginia Tech startup BC Genesis (Blacksburg, VA) is focusing on cartilage repair and meniscus replacement. “The technology should reach the market a few years from now,” Gatenholm says. “Maybe the first product will be a coating for existing products because of the bacterial cellulose’s excellent compatibility.”