For years biologists were so focused on the internal workings of cells that they pretty much ignored the “glue” that holds those cells together in a body, human or otherwise. And yet once researchers started looking deeper into the stuff between cells, known as the extracellular matrix, they began to realize just how dynamic the whole arrangement is. Not only does the overlooked matrix provide the biological scaffolding necessary to keep animal tissues and organs from dissolving into a gooey mess, but it also releases molecular signals that, among other things, help the body heal itself.
Building on this insight, investigators are now developing a new approach to tissue engineering—one in which the regenerative power of nature's own scaffolding plays a starring role. The idea is to harvest extracellular matrix from, for example, pigs and implant it in patients suffering from a large internal injury (after first stripping away the components that would have triggered a destructive attack by the recipient's immune system). The newly placed scaffold would then release molecules that attract semispecialized stem cells from the rest of the body to fill the various niches and to differentiate into exactly the type of tissue that should be there. Eventually even the implanted latticework would be replaced with human proteins and fibers, entirely erasing all trace of its barnyard origins.
Researchers are turning this vision into reality at an incredibly fast pace. Less than a decade ago surgeons started using extracellular matrix to repair abdominal hernias, basically weak spots in the muscles and supportive tissue that surround the intestines. Currently they are trying to grow new tendons inside the body, and in the not too distant future they hope to regenerate major muscle groups and even organs on a regular basis. Not surprisingly, the U.S. Department of Defense, which has developed a grim expertise in caring for soldiers who have had holes torn into their chest, arms and legs by explosive devices in Iraq and Afghanistan, funded many of these investigations with tens of millions of dollars.
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Scarring vs. Regrowth
Few researchers are as well poised as Stephen Badylak, deputy director of the McGowan Institute for Regenerative Medicine at the University of Pittsburgh, to help propel the field forward. Badylak began his career as a veterinarian, then received a Ph.D. in pathology, followed by a medical degree. “It's not a very practical way to train,” he notes, “unless you're prepared for a huge amount of educational debt.”
Badylak believes extracellular matrix may one day prove particularly beneficial to the survivors of explosions. The mammalian body, he notes, has limited ways in which it can respond to injury. Small wounds, such as paper cuts, disappear after inflammatory cells flood the area, fighting infection and removing damaged tissue. Complete replacement of normal skin (without a scar) soon follows. Soldiers who survive a roadside bombing, on the other hand, may lose 20 to 80 percent of the mass in a particular muscle group. In such severe cases, the researcher says, the injury exceeds the body's ability to regenerate tissue and the gap gets filled with dense scar tissue, thereby connecting the remaining tissue parts but also leading to loss of function. In these cases, the best option may be to amputate the limb and fit the wounded warrior with a prosthetic that provides a broader range of motion.
Badylak and his colleagues are now using extracellular matrix to treat 80 such patients with grave muscle injuries incurred at least six months previously. After an intensive regimen of physical therapy, designed to make sure the body has replaced as much muscle as it possibly can on its own, surgeons reopen the old wounds, remove any scar tissue that has formed, put in the biological scaffold and attach it to nearby healthy tissue.
Early results are promising, the veterinarian-physician-tissue-engineer says. Biopsies of treated muscle have shown the same biochemical changes that investigators saw when developing the technique in animals. If all continues to go well, Badylak hopes to publish findings from the first five patients later this spring or summer.
Learn more about regenerative medicine at ScientificAmerican.com/apr2013/regenerative-medicine
