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Regenerating lost limbs

Thanks to body armor and medical advances on the battlefield, soldiers suffering injuries in the current Iraq conflict are surviving at a rate of 9 to 1—a significant improvement over the 4 to 1 ratio of the Vietnam War. Although armor protects the core body, limbs are still vulnerable. Data gathered by the U.S. Senate reveal that about 6 percent of soldiers injured in Iraq require amputations—that’s twice the rate of previous wars.

Someday, however, these soldiers may not only survive their injuries—they may be able to recover what they’ve lost, thanks to University of Pittsburgh research.

Tom Gilbert, a Pitt assistant research professor, holds up a funnel-shaped object that looks like it’s made of plastic. It’s a simple structure, Gilbert says, but it represents technology that could assist the body in the regeneration of organs and other body parts—including entire limbs.

Gilbert (ENGR ’06G), who earned a doctorate in bioengineering at Pitt, belongs to a team that’s exploring new ways to grow tissue using a form of bio-scaffolding. The work is centered at the McGowan Institute for Regenerative Medicine, a venture of the University and UPMC. The group’s research is based on the findings of Stephen Badylak, a research professor in the School of Medicine’s Department of Surgery. About 20 years ago, while a faculty member at Purdue University, Badylak and his colleagues were researching how to repair an aorta—the body’s largest artery, originating in the heart. The group experimented with tissue from a pig’s digestive system. To prevent an immune rejection, the team removed all the cells from a portion of intestinal tissue, leaving just the collagen that makes up the tissue. They grew their collagen-cell creation to form a network of interlaced cells, much like a scaffold. Then, they implanted the bio-scaffolding to see whether it would repair tissue damage in the aorta.

The experiment worked well. So well, in fact, that Badylak and his team had a difficult time finding the scaffolding when they examined the aorta eight weeks later. The tissue seemed to improve healing in a site-specific way; the scaffolding didn’t just serve as a patch, it became something that was nearly identical to an aorta.

“They later found that if you put the scaffolding in an aorta, you got an aorta. If you put it in a urinary bladder, the tissue would be similar to the urinary bladder. If the scaffold is used to repair a tendon or a ligament, you would get tendon or ligament tissue,” Gilbert says. Clearly, it now seems possible to help the body regrow strong natural tissue in a variety of organs and other body parts.

The researchers are trying to understand the mechanisms by which these scaffolds work, and it appears that the scaffolding’s degeneration—it dissolves within 90 days—encourages the body to recruit its own stem cells from bone marrow to the site of the injury, allowing the body to create the site-specific tissue it needs.

Further experimentation with scaffolding made from a single layer of pig bladder tissue, like the funnel-shaped example Gilbert displayed, produced even more encouraging results. The treatment has been so promising that the device will be used in clinical trials in Pittsburgh early this year. The eventual goal is to regrow healthy esophageal tissue previously damaged by Barrett’s esophagus, a pre-cancerous formation of the innermost layers of the esophagus.

Gilbert thinks Badylak’s research team at the McGowan Institute is about four or five years away from developing a similar treatment for damaged trachea and will soon begin focusing on vocal cords. In addition, McGowan researchers William R. Wagner, associate professor of surgery, chemical engineering, and bioengineering, and Michael Sacks, William Kepler Whiteford Professor of Bioengineering, have developed a process that joins cells with polymer nanofibers to form scaffolding that may one day help repair or replace damaged soft tissue such as pulmonary valves. Their efforts earned them a place in Scientific American’s 50 for 2006, a recognition awarded by the magazine to those making key advances in science and technology.

The wildest possibilities of this technology already have found success on a small scale: Badylak’s scaffolding has been used twice to regenerate lost fingertips. Last May, the U.S. Department of Defense’s Advanced Research Projects Agency asked Badylak, who also directs the McGowan Institute’s Center for Pre-Clinical Studies, to oversee a $3.7 million grant and coordinate a national research project to study wound healing and tissue restoration. The aim is to study certain animals—such as salamanders—that have the ability to regenerate tissue. The goal is to identify specific elements, such as cells and scaffolding, that would make regeneration of tissue—and perhaps entire limbs—possible in humans.

For some soldiers, such research could prove to be the difference between living and thriving. —Allison Schlesinger

Breakthroughs in the Making

Doctor Roboto

Poised above the operating table like a giant, curious stork, a mechanical “surgeon” performs a tricky procedure on a patient’s lung tumor. Even as the patient breathes, CyberKnife precisely zaps the tumor with high-powered X-ray beams, destroying cancer cells without causing damage to surrounding tissue.

It used to be nearly impossible to perform laser surgery on a moving target. Not anymore. Thanks to a program called Synchrony, developed by Pitt Professor of Radiation Oncology Cihat Ozhasoglu and his team, CyberKnife can deliver cancer-killing X-rays to moving tumors with accuracy up to a few hundredths of an inch.

The Eyes Have It

As the graduate student scans her bookshelf for a particular volume, she probably doesn’t realize that her eyes are making tiny jumps, like film flickering through a projector. In fact, everyone’s eyes make such jumps, called saccades, and yet we all see the world in smooth succession. Why that’s so has been a longstanding puzzle in neuroscience. Now, Marc Sommer, a Pitt assistant professor of neuroscience, and Robert Wurtz of the National Eye Institute have found a neurological circuit that allows the brain’s visual neurons to shift their receptive field in the split second before a saccade, keeping our visual landscapes nice and steady. Their work was recently published in the prestigious journal Nature.


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