Some 100,000 people tear an anterior cruciate ligament (ACL) in their knee each year, typically while playing soccer or basketball. Now epidemic in teenage girls, this knee injury is notorious for not healing. Even when it's stitched back together, 90 percent of repairs fail within five years. So surgeons now recommend reconstruction—complete removal of the torn ligament and replacement with a tendon graft. While this allows patients to return to sports in the short term, many will develop early arthritis of the knee.
Martha Murray, MD, and colleagues in Children's Hospital Boston's Department of Orthopaedic Surgery took a closer look, and saw that torn ACLs try to heal themselves—cells migrate to the wound, growth factors are secreted and blood vessels appear—but that the ends never join. What's missing, they realized, is something to bridge the gap. In most torn ligaments, a blood clot acts as a temporary bridge until arriving cells can fuse the ends. But in the ACL, joint fluid dissolves the clot, washing the bridge away.
So Murray's team created a gel made of collagen (which isn't easily dissolved) and platelet-rich blood plasma and inserted it in the torn ACL in animal models. Cells soon migrated in, regenerating ligament tissue and mending the tear. Murray will soon publish findings showing 50 percent return of strength six weeks after ACL injury.
Her group next tried gene therapy—before inserting gel in the tear, they "seeded" it with a virus carrying a growth-factor gene. Cells crawled into the gel, picked up the virus and its gene, and began making the growth factor (Molecular Therapeutics, Aug. 2004). It's hoped such refinements will speed the healing process.
With funding from the NIH, the Center for Minimally Invasive Technology and the National Football League, Murray hopes to extend her regeneration technique to human patients and to other injuries like meniscus and rotator-cuff tears. The final goal is to accomplish the fix arthroscopically—via two small knee incisions, a camera to view the tear and a "gun" to squirt in the gel.
