Hurt-Knees Rx: Surgical method promotes ligament regeneration

Artificial knee ligaments incorporating live cells led to growth of new ligament tissue in recent experiments in rabbits. The technique could eventually provide an alternative surgery for athletes and others with knee injuries.

NEW GROWTH. Ligament (arrow) is vulnerable to damage in the human knee (left). Cross-section of a recently developed artificial ligament (right) 12 weeks after surgery shows new ligament tissue (green indicates collagen, purple indicates cells) filling the spaces between the polymer threads (white) of the implant. Artville; PNAS

Each year, more than 200,000 people in the United States experience tears to a knee ligament called the anterior cruciate ligament, or ACL. Damaged ligaments heal poorly if at all, so in the standard repair for ACL injuries, a surgeon cuts a piece of healthy ligament from another part of the patient’s leg and uses it to replace the torn ligament. But harvesting the healthy ligament can cause long-lasting pain and limit leg function.

The new artificial ligament, developed by Cato T. Laurencin of the University of Virginia in Charlottesville and his colleagues, may eventually enable doctors to avoid the extra surgical step.

“The hope is to make the ACL reconstruction a simpler procedure where we would move away from having to harvest the tissue,” Laurencin says.

Surgeons have inserted synthetic replacement ligaments into people, but these implanted prosthetics often break. “The problem with a prosthetic is that, over time, the prosthetic will eventually fail because it doesn’t regenerate,” Laurencin says.

To promote regeneration of ligament tissue, Laurencin and his colleagues worked with rabbit-ligament cells. Those cells generate new tissue only when they’re embedded into a specific kind of scaffolding. The researchers created a braided mesh with the right pore size—about 200 micrometers—by weaving together strands of a polymer called polyL-lactide.

When they implanted the cell-carrying polymer into knee joints of six rabbits, the scientists found substantial regeneration of ligament tissue after 12 weeks. Because the polymer is biodegradable, new ligament slowly replaces the prosthetic.

“This is the first technique that [in animals] has demonstrated such a remarkable level of ligament regeneration,” Laurencin says. Twelve weeks after surgery, the implants supported about 30 percent as much tension as an uninjured ligament does. That measurement compares favorably with that observed for the current standard surgical technique, which restores about 15 percent of normal strength in a similar time period, the researchers report in the Feb. 27 Proceedings of the National Academy of Sciences.

“I think it’s a good first step, but there are certainly some major challenges ahead before something like this can be approved,” comments Steven D. Abramowitch, a bioengineering professor at the University of Pittsburgh. Half the rabbits eventually suffered ruptures in the implants, but Laurencin notes that the animals moved around freely after surgery and didn’t stay off the repaired knee or do rehabilitation, as a human patient would.

Laurencin says that the next step in developing a clinical procedure will be to do longer trials in rabbits that include rehabilitation.

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