Dr. Cato T. Laurencin had already earned a PhD in biomedical engineering when he started a fellowship in sports medicine, a job that got him involved in fixing lots of torn knee ligaments known as ACLs.
“It just seemed to me that there might be a better way to be able to approach this,” said Laurencin, now a professor of orthopaedic surgery and director of the Institute for Regenerative Engineering at the UConn Health Center.
Fixing a torn ACL — the anterior cruciate ligament, which keeps the shin bone from sliding out in front of the thigh bone — generally requires implanting tissue from another part of the body. What if, Laurencin wondered, you could instead engineer a ligament that would regenerate?
At the time, Laurencin said, many people didn’t think it would be possible.
But 20 years later, he’s getting closer to doing it. There’s a clinical trial underway to test a new type of ligament Laurencin invented, which has already regenerated ACL tissue in animals. If the trial is successful, Laurencin said the next step would likely be a large clinical trial in the U.S. and seeking approval from the Food and Drug Administration to put the ligament into widespread use.
It’s part of the development of a field Laurencin calls regenerative engineering — research built on the tools made available through tissue engineering, material science, developmental biology and stem cells, aimed at regrowing living tissue.
Like the end of a rope tearing
There are an estimated 200,000 ACL injuries each year, and 100,000 reconstructive surgeries for them.
Typically, a torn ACL won’t heal on its own, so people who are active usually require surgery, said Dr. David Geier, an orthopaedic surgeon and sports medicine specialist in South Carolina and a member of the American Orthopaedic Society for Sports Medicine.
But a surgeon can’t just sew the torn ligament back together. “It’s sort of like the end of a rope tearing. It’s not like a clean break,” Geier said. “There’s nothing really to sew back together.”
Instead, surgeons use other tissue to replace the ACL, typically from tendons taken from the hamstring or another part of the knee. It’s more common to use a patient’s own tendon, especially among athletes, Geier said, although tissue from cadavers can also be used, particularly for less active patients.
Success of the surgery is often described in terms of how common it is for patients to return to sports, and Geier said studies have offered varied pictures. Some have found that around 90 percent of patients return to sports one year after the surgery, while others show the rate is closer to 50 to 70 percent.
Geier, who is not involved in Laurencin’s research, said the techniques for ACL repair have been tweaked, but the overall method hasn’t changed significantly in the past two to three decades.
“If there’s a way that makes procedures less invasive or [to] create something that makes the ACL heal on its own, that would be a huge break,” Geier said.
Making the body heal itself
In a patient with a torn ACL, the stump that remains contains a storehouse of nutrients and stem cells, which have the potential to grow into new tissue. Laurencin’s method involves using those cells and others that are already present, by placing a specially engineered “matrix” where the ligament should be. Cells can attach to it, creating new tissue.
“In many ways, we utilize the patient’s own body as a bioreactor, if you will, to be able to make the tissue,” Laurencin said.
It took years to create the matrix, which had to have the right mechanical and chemical properties to allow for regeneration. Laurencin worked on it with James Cooper, a former PhD student who is now a professor at Rensselaer Polytechnic Institute in New York.
The matrix, the L-C Ligament, is named for Laurencin and Cooper.
Research in rabbits showed that the matrix could regenerate an ACL. For the past two years, it was studied in sheep. The clinical trial in humans began in the Netherlands in June.
The L-C Ligament is designed to provide support for the knee as soon as it’s implanted. It takes between a year and 18 months to fully regenerate an ACL, Laurencin said.
The device was recently patented. The patent-holder is Soft Tissue Regeneration, a New Haven-based company Laurencin co-founded. The company has received funding from the state’s Connecticut Innovations, which gives the state a share of the company.
“We’re very excited about it,” Laurencin said.