Smart Tissue
Every year, Sitaram Emani and his fellow cardiac surgeons at Children’s Hospital Boston operate on hundreds of kids who need a new bit of tissue to repair faulty blood vessels. The current options for the patches and arterial grafts used by the surgeons—tissue harvested from pigs, cows, or human cadaver donors—may work for a while, but have a tendency to harden and scar, constricting blood-flow. Worse, they don’t grow along with the child’s cardiovascular system, which means, Emani says, “they may need to be replaced every couple of years,” requiring several follow-up surgeries.
Joyce Wong
Emani has tried growing tissue on biodegradable polymer scaffolds, using sheep as patients, but the results have been disappointing. “It feels like you’re putting a very stiff material into the body,” he says. Finding an alternative that’s durable and grows predictably along with the patient is what Emani calls “the holy grail” of tissue engineering. And now, he may have found it, thanks to an international collaboration of researchers led by Joyce Wong, a Boston University associate professor of biomedical engineering.
Wong has been working to perfect a tissue-growing technique pioneered by Teruo Okano, director of the Institute of Advanced Biomedical Engineering and Science at Tokyo Women’s Medical University. Instead of seeding cells on a biodegradable scaffold, Okano developed a way to culture sheets of a patient’s cells onto an engineered “smart” material that releases the fully grown cell sheet in response to a change in temperature. Wong's lab teamed up with Okano’s group to add microstructure to these cell sheets by printing a pattern of proteins directly onto the "smart" material to generate microstructured cell sheets. Elizabeth Bartolak-Suki, director of R&D for the Massachusetts-based biomedical startup Cellutraf Scientific, has been helping Wong fine-tune the cell-to-cell signaling of the tissue sheets, which can be layered into patches or rolled into arterial grafts in order to achieve a cell structure that closely matches a child’s original tissue, ensuring durability and predictable growth.
“You want it to grow in a particular way, and not to overgrow,” which can lead to blockage, says Wong. “We want to understand the basic science of what’s controlling the behavior of the cells because you can’t just throw these cells together and hope they become a tissue.” Take away the scaffold and the engineered patches and grafts, grown with the patient’s own cells, should come very close to matching the child’s naturally growing arterial tissue.
The work earned Wong a 2008 Individual Biomedical Research Award from the Hartwell Foundation of Memphis. Given for exceptional work in applied biomedical research to advance children’s health, the award includes $100,000 of funding annually for three years.
Wong will use some of the money to build a customized “bioreactor” that can mimic the physiological conditions of a child’s cardiovascular system, including temperature, pressure, and fluid flow. When the system is completed, hopefully by the end of 2009, Wong and her colleagues will be able to observe the growth and performance of engineered tissue under near-to-life conditions. In the meantime, they’re busy testing the engineered tissue’s biochemistry, assessing its strength with a stretching machine, and poking it with needles to ensure it can be properly sutured.
In addition to engineering cell sheets with human cells specially harvested from blood vessels, Wong is also working with sheep cells in order to test the new tissue in Emani’s animal models, and with induced pluripotent stem cells—grown cells genetically reprogrammed into an embryonic-like state and thus capable of developing into any type of tissue—being developed by several researchers at BU’s medical school, including Darrell Kotton, an associate professor of medicine in the pulmonary section.
For Wong, the research is more than academic. She has a niece and nephew who were born with congenital heart problems, and Wong’s father had a heart attack when she was in graduate school. “You sit in all these seminars and read all these papers on heart problems,” she says. “But when they happen to someone close to you, they take on a much more personal meaning.”
Detecting Bad News Biomarkers
Tissue sheets engineered from a patient’s own cells may mean fewer surgeries and fewer complications for children who need arterial grafts and patches to repair faulty blood vessels.
Scientists from Boston University and the National Heart, Lung, and Blood Institute (NHLBI) are tracking down two of America’s biggest killers: heart attack and stroke.
They will be looking for new biomarkers—disease warning signs in the form of proteins, small molecules, or genes that are screened for in blood tests. The multipronged investigation is known collectively as the Systems Approach to Biomarker Research in Cardiovascular Disease (SABRe) and is funded by $7.6 million from the NHLBI, part of the National Institutes of Health.
Researchers will analyze blood samples from approximately 7,000 participants in the Framingham Heart Study, a multigenerational epidemiological study begun in 1948 by the NHLBI and run by BU since 1971 under NIH contract.
Currently, clinicians assess their patients’ risk for cardiovascular disease based largely on broad indicators such as blood pressure and cholesterol—relatively blunt tools for identifying who is at risk, says Daniel Levy, director of the Framingham Heart Study and of the NHLBI Center for Population Studies.
“There are a lot of people who don’t have one particular risk factor that stands out as very elevated,” says Levy, who is also a professor in the School of Medicine. “They might have marginal rates of various risk factors. And if we had better means of identifying their risk early on, we might be able to design better interventions.”