November 2014 update:
The FDA has approved first-in-human trials for the bridge-enhanced ACL repair technique. A total of 20 patients will participate. Ten will serve as an experimental group and they will undergo a bridge-enhanced ACL repair surgery. The other 10 patients in the study will have the standard ACL reconstruction procedure and serve as a control group.
The anterior cruciate ligament (ACL) is a powerhouse and the perplexing nexus of a sports injury epidemic.
Providing primary stability across the knee joint, the ACL is remarkably susceptible to rupture or tear, with more than 400,000 surgical reconstructions performed annually in the U.S.
In the 2013 National Football training camps, more than a dozen players were sidelined with ACL injuries. This spate of ACL tears is sure to ripple through high school and college football and soccer fields this fall.
A complete ACL tear is a devastating injury for athletes, typically ending the player’s season and requiring surgical reconstruction. Although many athletes return to the field after reconstruction and physical therapy, studies suggest as many as 80 percent will develop arthritis within 14 years of the injury.
Moreover, children and adolescents are not considered good candidates for ACL reconstruction. The conventional procedure requires surgeons to drill tunnels through the growth plates—the developing cartilage near the end of long bones—but this can disrupt bone growth.
Boston Children’s Hospital orthopedic surgeon Martha M. Murray, MD, wants to change the game plan for ACL injuries. Her research focuses on bio-enhanced ACL repair that uses a bio-engineered scaffold saturated with the patient’s own blood to stimulate healing and to promote clotting, which is essential for ligament repair.
Regrowing torn ligaments
The technique, which has been applied in animal models, is straightforward: During a minimally invasive procedure, the surgeon inserts the bio-engineered scaffold between the two torn ligament ends, threading sutures through a tunnel drilled in the femur, then through the scaffold and finally through a tunnel in the tibia. The torn ends of the ACL grow into the scaffold and the ligament reforms.
In other words, the ligament is repaired, not just replaced or reconstructed. Current surgical techniques, including advanced techniques performed at Boston Children’s Hospital, are limited to ACL reconstruction, which requires a tendon graft. That’s because the ACL is fairly unique among ligaments: It lacks the ability to heal itself.
What’s truly exciting, says Murray, is that bio-enhanced repair may minimize patients’ risk of arthritis, if results in a pig model hold true in humans.
The results of Murray’s most recent study involving pigs were published in the August edition of The American Journal of Sports Medicine. She and Braden C. Fleming, MD, compared four approaches: no treatment, standard ACL reconstruction, bio-enhanced ACL repair using the bioactive scaffold and bio-enhanced ACL reconstruction (combining the bioactive scaffold and a tendon graft).
As expected, the no-treatment group had miserable outcomes. The other groups fared better than no treatment and had similar outcomes for the mechanical performance of the ACL or graft in terms of stiffness, maximum load and anterior-posterior stiffness.
The bio-enhanced repair group, however, demonstrated one key difference: These animals lacked the typical pattern of cartilage loss associated with osteoarthritis.
“We never dreamed of seeing results this promising,” Murray says. “The bioscaffold was equal to the current standard—ACL reconstruction—in terms of mechanics and better in terms of long-term outcomes.”
The second half
Murray’s game plan has now turned to humans. As a first step in a series of regulatory hurdles, the researchers have established a Good Laboratory Practices (GLP)-compliant facility in the orthopedic research lab to construct a scaffold suitable for human use.
The first batch of bio-engineered scaffolds has been submitted for sterility testing, and all reports indicate it will pass and proceed to the next stage—biocompatibility testing. A biocompatibility pass, followed by data submission and a green light from the FDA, will allow the team to begin testing the scaffold in humans.
Like many of the athletes she treats, Murray is wholeheartedly bent on success. “If the FDA says the scaffold is ready for human use, we’ll start clinical trials. If not, we’ll keep working on it until we get there.”
The end game
Currently, physicians recommend that children and adolescents wait until their growth plates have closed (as late as age 17 for boys) to undergo ACL surgery.
But the consequences of postponing ACL reconstruction can be devastating, as even everyday activities pose a risk for cartilage injuries and meniscus tears. Plus, requiring a young athlete to avoid sports can have negative psychosocial consequences.
Lyle Micheli, MD, and Mininder S. Kocher, MD, MPH, at Boston Children’s Hospital pioneered the development of a specialized ACL surgery which can safely be performed on patients with open growth plates, but not all orthopedic surgeons are comfortable with the techniques. “In many regions of the country, kids with open growth plates are told they have no surgical options,” Murray notes.
In contrast, because the bioscaffold repair technique resembles a straightforward fracture repair, orthopedic surgeons without an arsenal of sub-specialized skills would be able to complete the procedure. Youth with ACL tears would have a new, less invasive choice, and their arthritis risk might be lower. So if the model succeeds in humans, the Murray team will have hurled a game-changing pass