By Johann Grolle
A mechanical arm snaps up a small plastic container full of a sloshing pink solution. A laser beam flits over the liquid, then another robot rolls up on a steel track, motor purring, and drizzles a few drops through hair-thin pipettes. A monitor records temperature, carbon dioxide and humidity levels.
A soft whirring is the only sound in this laboratory at the Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB) in the southwestern German city of Stuttgart. Sterile and sealed behind glass, these machines have just begun to produce an unusual product: human skin.
Each month, this skin factory will produce 5,000 discs of tissue about the size of a one-cent coin, with a projected price of 50 ($72) per unit. The product is a whitish color, almost transparent, though project director Heike Walles says it can also come in shades of brown.
The Birth of Tissue Engineering
The pieces of tissue swimming in their nutrient solution may look less than impressive, but the pilot project here is about more than just manufacturing skin. The process is meant to pave the way for a new era, one in which human tissue becomes an industrial product. The miracle of incarnation, which once only took place in the darkness of the uterus, is now happening under the cold neon light of an assembly facility controlled by robots.
This means that Heike Walles, the 48-year-old head of the institute's Cell and Tissue Engineering department, has finally reached her goal. A biochemist, Welles has dedicated her entire career to culturing tissue. One image that especially fueled her interest in this futuristic field was the famous photograph from the Vacanti laboratory at Harvard University. There, 15 years ago, brothers Jay and Chuck Vacanti created an ear-shaped cartilage structure and grafted it onto the back of a mouse.
When the Vacantis presented the world with photographs of their project, they also offered a bold vision of the future of medicine. They promised the dawning of a new era in the history of transplant medicine. Since human tissue could be custom-made, they said, there would never be a shortage of donor organs again.
The Vacantis also described how fully functional human hearts would grow in flasks and how livers would rise in incubators like loaves of bread. Chuck Vacanti even said it would be possible to produce entire limbs and provided a sketch of a synthetic arm. The brothers called their new industry "tissue engineering."
The First Pioneering Steps
Drawn by these promises, Walles signed on with the cardiac surgery department at Hannover Medical School (MHH) to learn about the production of arteries and heart valves. But she quickly realized just how naive the visionaries' dreams had been. "Researchers promised far too much at the beginning," she says. "At the time, it helped foster acceptance for the new technology. But, these days, patients and society are disappointed -- and rightly so."
Of course, tissue engineers continued to make headlines. Researchers at the Vacantis' lab then went one better by presenting the public with a heart the size of a cherry that beat away for 40 days inside an incubator. They even transplanted a synthetic lung into a rat that kept it alive for several hours. The scientists also instructed an artist in the art of cultivating tissue so that he could grow a steak in a petri dish. (The artist eventually admitted that the artificial meat had a horrible texture and taste hard-to-define taste.)
Elsewhere, surgeons reported success in human trials as well. In North Carolina, for example, doctors grew bladders from stem cells, which they then succeeded in implanting in children with malformed organs.
In an even more spectacular experiment in the northern German city of Kiel, doctors ventured to reconstruct a patient's jaw after it had been eaten away by a tumor. They designed the desired section of bone on a computer, used the design to fashion a mesh frame of titanium wire, and then sowed this with the 56-year-old patient's bone marrow cells. Then they allowed it to mature in his back muscle for seven weeks before attaching it to his face.
Still, all of these efforts were isolated cases and heroic pioneering acts that never made their way into daily clinical practice. Indeed, tissue engineering remains a refined handcraft, one that requires a great deal of tinkering and patience. Bioengineering laboratories now grow dozens of different cell types on spongy, rubbery or gelatinous frameworks, but most of these constructions are not suited for use in humans.
Blood circulation, in particular, has presented researchers with many problems, and attempts have repeatedly failed to produce blood vessels that can supply synthetic organs with oxygen and nourishment.
Cartilage is the only type of tissue uncomplicated enough to be manipulated with relative ease. Each year, surgeons in Germany implant around 600 pieces of artificial cartilage, and the number of patients with lab-grown cartilage cells infused into their damaged knee joints or spinal disks has climbed into the thousands. But scientists looking to make other types of tissue ready for clinical use find themselves facing far greater obstacles.
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