Bioengineering technology may aid athletes and boomers
by Marjorie Howard

In an elongated basement room off a dull, gray corridor on Boston Avenue in Medford, a group of researchers is entering a new phase in a remarkable journey. The trappings of their work are mundane: a collection of stainless steel tubes at the back of the room, a large pipe looped in an oval on the floor, a couple of white boards scrawled with numbers and calculations and several two-pound spools of silk.

Greg Altman, A97, G02, president, CEO and founder of Tissue Regeneration, says his company has prospered because of Tufts’ ability “to knock down walls and borders.” © Chris Churchill

This is the home of a company called Tissue Regeneration Inc. (TRI), partly owned by Tufts University and created through an informal collaboration among several schools and departments at Tufts. The company’s work may transform major surgeries performed on hundreds of thousands of people a year into procedures that will require far less rehabilitation.

Tissue Regeneration is on the verge of preclinical trials for a new procedure that would allow the body to grow its own anterior cruciate ligament, a commonly injured knee ligament. Now the company is going even further: After waiting for 20 months, the company learned in May that it won a highly competitive $2 million Advanced Technology Program grant from the National Institutes of Standards and Technology to apply what it is learning about the ACL to the rotator cuff tendon in the shoulder.

While most people have heard about the rotator cuff problems of major league baseball pitchers, they are not the only ones who suffer from shoulder problems. According to Greg Altman, A97, G02, president, CEO and founder of Tissue Regeneration, 650,000 people each year require medical attention for rotator cuff injuries, and 150,000 have surgery—all due to wear and tear of the tendon. As for the anterior cruciate ligament, another 200,000 people undergo knee replacement surgery each year and spend about six months in rehabilitation.

Knocking down walls
While ligaments connect bone to bone, tendons connect bone to muscle. A baseball pitcher who hurls 90-mile-an-hour fastballs may tear his rotator cuff tendon, but in the average person, the tendon simply wears away over time. Hairdressers and electricians, who repeatedly raise their elbows above their shoulders, are especially prone to rotator cuff problems, but so is the average baby boomer.

As the company begins to expand its work, Altman says that without Tufts, none of this would have happened. “If not for the ability of Tufts to knock down walls and borders,” he says, “we wouldn’t have this project. At MIT or Harvard, there would have been a turf battle. We wouldn’t have the cooperation between different departments. In addition, both undergraduate and graduate students have played key roles as a result of Tufts’ emphasis on [students’] hands-on involvement in research.”

He ticked off some of the Tufts departments that have been involved with Tissue Regeneration: biomedical, mechanical, chemical and biological engineering in the School of Engineering; the biology department, the School of Medicine and Tufts-New England Medical Center.

And he added an unexpected element: the Department of Athletics, where former Athletics Director Rocco Carzo taught Altman about leadership, and head football coach Bill Samko taught Altman the values he uses in his work every day.

“Every principle I learned from him [Samko] I apply at this company,” he says. “Bill taught me that there are many things in life I can’t control. What is under my control is how much I care and how hard I work. At the end of each day, I go home and check in with myself: Did I get accomplished what I needed to, or did I waste time?”

Athletics as motivator
It was through sports that Altman first became interested in finding a way to repair the ACL. A chemistry major, he played offensive tackle for the Tufts Jumbos and planned to go to medical school. Then he tore his ACL. He missed a year of football but was eligible to play another season after he received his undergraduate degree in 1997. He began a master’s degree in engineering. “Football caused me to go to graduate school, nothing else,” he says bluntly. “I wanted to play for one more year.”

Altman took a course with David Kaplan, professor of biomedical engineering, who required the class to write a mock grant proposal to improve an existing medical device. Because of his injury, Altman started thinking about ways to improve the repair of the ACL ligament. When it tears, the ACL cannot grow together unless it has a scaffold that allows it to reconnect, similar to the way a vine grows on a trellis. Currently, surgeons repair the ACL by taking a piece of tendon from either the patella or the hamstring to reconnect the torn ligament. After the surgery, patients undergo a long rehabilitation period to strengthen the area from which the tendon has been removed.

Dr. John Richmond, M76, formerly an orthopedist at Tufts-New England Medical Center, was the physician who repaired Altman’s ACL, and Altman began asking Richmond questions during follow-up visits for his knee. It turned out that Richmond, then an orthopedic surgeon at Tufts and now chairman of orthopedics at New England Baptist Hospital, had been trying to develop a material with which to replace the ACL and had devised a plastic implant to act as a scaffold. But because plastic does not break down, it did not prove to be a good solution. “We wanted something that slowly degrades but still provides enough time for the body to regenerate tissue,” says Altman.

From his discussions with Richmond and Kaplan, Altman came up with the idea of using regenerative material, that is, to find a way to have the body create its own ligament. The idea was to harvest adult stem cells, stimulate them to grow into ligament cells in a bioreactor and then bank them prior to surgery.

He wrote his proposal for his class with Kaplan and filed for a patent. Altman formed a company with Richmond and Kaplan as co-founders and began applying for grants to develop the research. Another company co-founder is Gordana Vunjak-Novakovic, who co-taught the biomedical engineering course with Kaplan. Altman’s company received two Small Business Innovative Research grants totaling $850,000 from the National Institutes of Health.

“With that, we were essentially off to the races,” Altman says. Other private seed capital was obtained to sponsor research at Tufts, which then led to more grants, including one from the National Science Foundation. In addition, Tissue Regeneration Inc. recently raised several million dollars in venture capital.

The silk solution
Altman’s first idea would have meant that patients could grow their own ligaments using adult stem cells, a bioreactor and collagen fibers. He spent several years on this idea, but the collagen never proved strong enough. After the project failed, Altman renewed his commitment to solving the problem and decided to earn a Ph.D. in biomedical engineering, which he completed in 2002.

Meanwhile, he turned to Kaplan, who suggested silk, a material on which Kaplan is one of the world’s leading experts, might provide the right scaffolding. The idea was to use a small bundle of silk threads that would reconnect either the ACL or rotator cuff tendon. Ligament or tendon tissue would then grow and develop around the silk strands. Ultimately the silk would biodegrade and no longer remain in the body.

Altman and his colleagues have had to overcome some obstacles. Silk is inelastic, and the research team had to learn how to work with the material. “We had to find a way to create a structure that has very specific mechanical properties,” Altman said. “TRI can now process silk that can be implanted into the body. The beauty of silk is that before it degrades, it provides the body time to regenerate functional ligament or tendon tissue.”

Working with Altman have been some 20 undergraduates, five of whom have decided to pursue their doctoral degrees at Tufts. Rebecca Horan, E02, is working on her Ph.D. in biomedical engineering, but as an undergraduate mechanical engineering major, she earned credit as the co-inventor of the patented silk structure used to create the tendon and ligament scaffolds.

Altman also likes to recruit athletes: He has employed three Jumbo offensive tackles and all-American softball pitcher Jodie Moreau, A02, who recently had reconstructive surgery on her rotator cuff. Second- and third-year Tufts medical students and postdoctoral fellows also have worked on the project.

“Students have the opportunity to do research, much in the same way Dr. Kaplan allowed me to run with the project. He taught me to delegate responsibility, regardless of age or status,” Altman says.

Altman expects to initiate ACL and rotator cuff trials in humans by the end of 2006 and hopes to have both ligament and tendon products on the market shortly afterward.