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Tool for knee surgery will help rebuild ACL

When Martha Murray, MD, was in graduate school, a close friend tore an anterior cruciate ligament (ACL), a key component in knee movement. Dr. Murray was surprised that it took so long to heal, and frustrated that there didn’t seem to be better methods to get her friend back on his feet. This nettling memory was a key factor in her career direction, for she has chosen the repair of knees as her specialty in the orthopedic world.

Dr. Murray is a surgeon and a researcher today at Children’s Hospital Boston, and is one of the top knee specialists in the area in treating sports injuries. Her research focuses on the stimulation of healing of tissue inside joints, particularly the anterior cruciate ligament (ACL) and meniscus of the knee.

Treatment of these injuries remains one of the most challenging problems facing orthopedic science today. These tissues have minimal intrinsic ability to repair or regenerate in the human and thus injuries of those tissues are often treated by excision of the injured tissue and sometimes replacement with autograft or allograft tissue. However, these procedures lead to a high rate of premature osteoarthritis of the knee (as high as 80 percent at 14 years after an ACL tear).

Dr. Murray’s lab studies the regenerative potential of the native tissues after injury, and has found that the cells in each of these tissues have great potential for proliferation, extra-cellular matrix production and migration if provided with the appropriate environment. The Murray lab has identified the premature loss of fibrin clot (secondary to the presence of plasmin in the synovial fluid) as the likely etiology of the failure of these tissues to heal. Work continues to focus on development of a substitute for fibrin clot, which allows healing of tissues within the joint to proceed the way healing of tissues outside the joint can.

CIMIT was an early believer

Encouraged early in her research career by CIMIT, she has developed a new approach with a unique medical tool to treat such knee problems. Her research could result in a breakthrough platform for treating knee injuries, and could enable both young athletes and mature adults to pursue more active recreational lives. Medical-device companies have shown an early interest in her work. They like her science and are also impressed by her dedication and drive. But she is opting to continue her research within the academic rather than industrial environment.

Dr. Murray is not a sports fanatic, though she played soccer and was on the swimming team when a high-school student in Sherborn, MA. But she is a dedicated fan of strong bodies, starting with knees.

A problem that she often sees begins when a patient tears the ACL ligament inside the knee joint. Unlike other tissue, the ACL doesn’t heal when it’s stitched together. This had led to the current dogma that ACL rupture needs to be treated by replacing the tissue.  Dr Murray and her team thought that perhaps instead, it would be interesting to look into why the ligament does not heal, and what biologic factors might be useful in helping it successfully heal rather than replacing the ligament with a tendon graft. Her first area of research was the cell, and she and her team developed a material that would clot and form a scaffold to be used as the basis of rebuilding. So she and her team worked to develop a cell-friendly gel that could be used as a bridge, or scaffold, to enable clotting to support a minimally invasive procedure. And a second challenge was how to deliver the right mixture at the right temperature to the site. To research the problem, she turned to CIMIT.

CIMIT and Dr. Murray have proved to be a good team. First CIMIT helped with encouragement. She recalled, “When you’re just starting out in your career as a researcher, and you write grants, and people write back and say, ‘This is a terrible idea,’ you can only get five or six of those before you want to quit. So when CIMIT says, ‘We’re not sure about this but go meet with this person.’ And then you meet that person, and he says great idea, you just have to couch it differently,’ it’s encouraging. Because when you’re doing something truly novel and advocating a different course of action, something that goes totally contrary to what everyone has said for 25 years, it’s hard to find support. But CIMIT was there and provided backing.”

CIMIT helped the Murray team with early grants, which enabled her to gather enough data to successfully attract funding from the National Institutes of Health and other sources.

MIT engineers help design a medical-device prototype

CIMIT, in addition, was instrumental in putting Dr. Murray in touch with engineers at MIT to help with the mechanics of creating a tool that could deliver the gel into the knee. Through the CIMIT community, she was introduced to MIT graduate engineering students under Professor Alex Slocum, PhD, to get guidance regarding her device. She was invited to present her concept to the HST 2.75 engineering class, which is a CIMIT-initiated course at MIT designed to bring young engineers into contact with doctors who are intent on solving a medical problem.

Dr. Murray told them she needed a tool small enough to fit through an incision that would be capable of mixing and then injecting a gel that would allow torn ACL tissue to grow before the gel hardened. Dr Slocum’s graduate student team helped Dr Murray design and manufacture an instrument that could place the gel into the knee through a incision less than a centimeter long. An experimental tool is in its third version, and developers hope to have it in clinical trials in a couple years.

“The engineers have helped us a great deal,” said Dr. Murray. “They are working on a crucial component of the project, and they are enthusiastic, dedicated and smart. We’ve have really benefited from CIMIT helping us access some terrific engineering talent.”

After five years of experimentation, Murray’s team developed a gel that could be used as a bridge to enable blood clotting and a tool to deliver it. As the project grew, CIMIT provided advisory support, guidance on patent applications and identified industry partners. Murray’s research was also eventually funded by the National Football League. CIMIT continued to fund her novel approach to tissue repair to help her gain sufficient preclinical data to put her in position to get approval from the Food and Drug Administration.

Dr. Murray’s research has significant commercial potential, as national statistics show that there are about 200,000 ACL tears in the U.S. each year. Such a breakthrough platform would be a win-win situation for patients, who could get back to activity in the short term – and have a better chance to avoid knee replacements in the future.

"When you’re doing something truly novel and advocating a different course of action, something that goes totally contrary to what everyone has said for 25 years, it’s hard to find support. But CIMIT was there and provided backing.”

-Martha Murray, MD
Children’s Hospital Boston

Did You Know?

• The ACL is one of four major ligaments of the knee and provides almost 90% of the stability to the knee joint.

• ACL injuries are one of the most common sport related knee injuries.

• Approximately 100,000 – 200,000 people in the United States acquire a torn or ruptured ACL every year.

• Women are nearly three times more likely to have ACL injuries than men.

• The majority of ACL repairs that occur each year are done on young athletes (under age 25) and female athletes.

• ACL reconstruction is a highly successful operation. With good rehabilitation, 90% to 95% of individuals who undergo this surgery can expect to return to full sports participation within six months.

• ACL repair procedures lead to a high rate of premature osteoarthritis of the knee (as high as 80 percent at 14 years after an ACL tear).

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