Tufts University Researchers Engineer First "Custom-Made" Human Knee Ligaments From Adult Stem Cells

Greg Altman, a Tufts doctoral candidate, presented the findings at the 48th annual meeting of the Orthopaedic Research Society in Dallas. Altman has been conducting this research under the guidance of David Kaplan, director of Tufts' Bioengineering Center (www.ase.tufts.edu/biotech) and Dr. John Richmond, professor of orthopaedic surgery at Tufts' Medical School. Altman has been pioneering the ligament engineering strategy over the past four years.

The Tufts team is developing a patented ACL product that can be custom-engineered from a patient's or donor's adult stem cells, which may be readily obtained from bone marrow. Altman also has formed a company, Tissue Regeneration Inc. (TRI), to develop and market the product. The company already has received seed capital from government grants, including the National Institutes of Health.

In the process, ligaments are grown and "banked" prior to knee trauma so they will be readily available at the time of reconstruction.

"The technology for this tissue repair and ligament growth could fundamentally change the way we treat this very common injury," said Altman. "And since the ACL has poor healing capabilities, our new ligament tissue could significantly reduce the recovery time to just weeks--rather than months--for professional athletes and sports enthusiasts compared with current surgery practices."

Approximately 200,000 ACL surgeries were done in the U.S. last year, costing an estimated $3.5 billion, plus another $200 million for subsequent therapy. Worldwide, another 400,000 people last year injured this ligament. The costs associated with surgery can range from $10,000 to $25,000 per procedure, and up to $1,200 in physical therapy. In addition, the cost to individual sports teams or players also is significant--including lost championships and declining ticket revenues.

The research may also be particularly meaningful to female athletes, as recent studies show that female soccer and basketball athletes are three- to four-times more likely to injure their ACL than males.

According to Richmond, who is also chief of adult orthopaedics and sports medicine at Tufts-New England Medical Center, "Orthopaedic surgeons and active people all over the world will find great hope in this research. We look forward to the day when we'll be able to replace a damaged ligament with a healthy new one, grown from our own tissue."

The ACL research presented at today's Orthopaedic Research Society meeting is a collaboration among experts from Tufts' Bioengineering Center, School of Medicine, Department of Chemical and Biological Engineering and Tufts-New England Medical Center. Additional contributors include faculty at MIT and in Switzerland.

"The Bioengineering Center is at the core of a multidisciplinary team at Tufts that draws from all the resources across the University," said Kaplan. The center is involved in a number of other projects that involve collaboration among faculty and students in disciplines ranging from medicine and nutrition to veterinary medicine, dental medicine, biology, chemistry, chemical engineering, physics and computer sciences.

To create the custom-made ligaments, the team of "tissue engineers" cultures cells in vitro in a specially designed bioreactor with a collagen or other suitable biodegradable matrix. The cells are then stimulated with multi-dimensional, mechanical forces that mimic ligament movement in the body to develop into living tissue. The bioengineered ligaments can be stored until needed by the patient or donor and then implanted immediately following knee joint trauma.

To date, no human clinical trials have been reported with tissue-engineered ACLs. Altman plans a long-term, FDA-relevant trial of ACL implants in goats later this year.

"Neither reconstructive surgery nor biological or synthetic prostheses can restore complete functionality to the knee without associated debilitating side effects such as pain, tendonitis, muscle atrophy and loss of function," said Altman, a former Tufts offensive tackle who experienced these side effects from his own knee surgery. Other common post-surgery problems have been infection and disease transmission, including gangrene.

Altman was a pre-season All-American football player at Tufts in the fall of 1996, when he had his season-ending ACL injury. He later served as an assistant coach for the Tufts football team.

"Following ACL surgery most people are on crutches for two weeks, can jog after two or three months, and can return to athletics after six months" said Altman. "But you don't feel like you have your knee back until 12 or 18 months after surgery. And 15 percent of those with an injured ACL never return to pre-injury activity levels."

Altman holds a bachelor's degree in chemistry from Tufts and expects to receive a doctorate degree in biotechnology engineering this May.

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NOTE TO EDITORS: Images, figures of the project and Altman's presentation at the Orthopaedic Research Society meeting are available at http://www.tufts.edu/communications/altman.htm

Tufts University, located on three campuses in Massachusetts (Medford/Somerville, Grafton and Boston) and in Talloires, France, is recognized among the premier research universities in the United States. Now in its 150th year, Tufts enjoys a global reputation for academic excellence and for the preparation of students as leaders in a wide range of professions.