Growing the Stuff of Life

For decades, scientists have been stymied in their attempts to study the living brain in the laboratory. Tufts’ Tissue Engineering Research Center (TERC) took a major leap forward on that front last year, doing the seemingly impossible: growing brain tissue outside of the body and keeping it alive for months. Now students in the lab can study what happens in traumatic brain injury: they drop a heavy weight on the tissue and then analyze the chemical and electrical changes in the cells.

TERC’s success in growing this tissue hinges on one material: silk. In fact, silk has proven key in growing a range of tissues at the center, including kidney, intestine, heart, lung, bone, cartilage, and ligament. David Kaplan’s eyes light up when he talks about the versatile material, which can be used to create everything from soft sponges to hard disks. “Every year we learn something new about it. You can make it mechanically match everything from bone tissue to brain tissue,” enthuses Kaplan, who is TERC’s director. “It’s biocompatible, FDA approved, and degradable in the human body.”

To grow tissues, Kaplan and his colleagues first must build a scaffold. That’s where the silk comes in. For brain tissue, they make hundreds of round, hollow “donuts” of porous silk sponges to simulate the structure of cortical tissue, and fill them with a collagen protein gel. They seed the collagen with cells—usually stem cells that can undergo distinct growth patterns. The cells used to grow brain tissue are derived from the brains of rats. Finally, the entire structure is bathed in a specially formulated chemical solution that keeps the cells alive.

After that, the cells simply take over, growing on the scaffold. In the brain tissue project, this resulted in functional neural networks in a remarkably stable structure. “We did not know how to direct the process, so we allowed the cells to do it themselves,” Kaplan explains. “But we had to create the conditions that made the cells want to do it.”

TERC’s tissue materials have been used to engineer three-dimensional models of organs for toxicology and drug testing. They have also helped researchers study such ills as cancer, obesity, and osteogenesis imperfecta, a genetic disorder that causes a person’s bones to break easily. Kaplan points out that working with lab-grown tissues “not only reduces animal use in research, but also reduces costs and provides data that is more relevant to human conditions.”

The center’s efforts have yielded innovative practical applications. “We work with clinicians around Boston and around the world,” often fielding requests for specific kinds of medical treatments, says Kaplan. “So our students will take on the challenge of making prototypes using the biomaterials in the center.”

Recently, the center created silk screws for pediatric bone surgery at Beth Israel Hospital and Boston Children’s Hospital. Silk screws could be an improvement over steel or titanium, especially since children’s bones grow so fast. The screws are strong enough to hold bones together, but they conveniently degrade as bone tissue regrows.

Earlier in the center’s history, Greg Altman, A97, G02, started a company to develop ligaments from silk. Bought by Allergan in 2010, the company now develops technology for breast tissue reconstruction. Meanwhile, Altman has gone on to establish a line of skin-care products through a new company of his, Silk Therapeutics. Two of Kaplan’s former postdoctoral associates, Mike Lovett, E09, and Tuna Yucel, have formed another company, Ekteino, which is developing implantable silk devices to deliver drugs for treating chronic diseases.

Josh Mauney, E99, E04, an assistant professor of surgery at Harvard Medical School and a staff scientist at Children’s, wants to use TERC research to help children who have bladder abnormalities. Doctors often treat such patients by implanting a piece of intestine into the bladder to increase its capacity, but the procedure is fraught with complications that can result in long hospital stays over time. Mauney’s alternative, an “off-the-shelf” silk-based graft, would be inserted into the bladder and embedded with proteins to stimulate the growth of new, healthy tissue. “This has high potential, especially in a pediatric hospital where kids are suffering from a lot of these congenital abnormalities,” he says.

Mauney anticipates that such a graft could eventually be used in other parts of the body, including the urethra and the digestive tract, and he thinks it might be ready for human trials in children in about five years. That timetable, lightning fast in the world of clinical medicine, is possible because the FDA has already approved silk as safe for the body in some applications.

With tissue engineering advances like these, Kaplan may never stop singing the praises of silk. “One of the glaring needs in the field for a long time has been the need for a better biomaterial,” he says. “That is a niche we have really filled.”

MICHAEL BLANDING is a Boston-based writer and a frequent contributor to Tufts Magazine and to Tufts Now, where this article first appeared.