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Monday 27th March, 2006
A surgeon at Children's Hospital Boston may have found a better
way to repair tears to the anterior cruciate ligament (ACL).
A surgeon at Children's Hospital Boston may have found a
better way to repair tears to the anterior cruciate ligament
(ACL), a knee injury suffered by more than 100,000 Americans
each year, particularly teenage girls. In the April Journal
of Orthopaedic Research, orthopedic surgeon Martha Murray,
MD reports that a collagen gel, enriched with blood
platelets, can stimulate natural healing of a partial ACL
tear, encouraging the body's cells to fill in the defect and
restore mechanical strength to the ligament.
"This is a first important step in showing that the ACL can heal
if we give it the right conditions," Murray says. "That's an
important shift from thinking that the ACL has to be completely
replaced after an injury."
ACL injuries are notorious for not healing well. Epidemic among
teenage girls ? who are five times likelier than boys to tear the
ligament ? they typically occur during sports that involve jumping
and pivoting, like soccer or basketball. ACLs are currently
reconstructed by replacing the torn ligament with a tendon graft.
This painful operation allows patients to return to sports after
significant rehabilitation, but it does not fully restore knee
mechanics, and does not prevent arthritis from developing years
Working with an animal model of a partial ACL tear, Murray's team
inserted a collagen gel, mixed with platelet-rich blood plasma, into
the wound. The gel provided a physical "bridge" between the torn
ligament ends, while the platelets churned out a variety of growth
factors. Compared with untreated knees, knees treated with the gel
showed greater defect filling at 6 weeks (43 percent versus 23
percent). The gel-treated ACL defects also had a 40 percent increase
in mechanical strength at 6 weeks, compared with just 14 percent for
Although she cautions that these results are preliminary and that
more work needs to be done, Murray hopes to eventually extend her
ACL regeneration technique to human patients, using platelets from
their own blood plasma to create a less invasive ACL repair that
would decrease recovery time and give athletes a knee with more
normal function. With funding from the NIH, the National Football
League, the Orthopedic Research and Education Foundation and the
Center for Minimally Invasive Technology (Cambridge, Mass.), she is
developing an arthroscopic approach that would squirt the gel into
the wound via two small incisions in the knee. Her team is also
trying to enhance the gel to speed the healing process.
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Until the 1970s, surgeons tried to repair ACL tears by sewing the
ligament ends back together, but the sutures nearly always failed.
Murray, who became interested in ACL healing while pursuing a
doctorate in materials science, wondered why this was so, and
eventually went to medical school to pursue the problem. Ligaments
should, in theory, heal easily--they're made of fibroblast cells,
which are workhorses in the body and easy to grow.
Examining torn ACLs at the microscopic level, Murray and colleagues
were surprised to find that the ligament tries valiantly to heal
itself--cells migrate to the wound, growth factors are secreted and
blood vessels grow to nourish the new tissue. But the ligament ends
never join. What's missing, Murray realized, is something to bridge
In most torn ligaments, a blood clot forms and acts as a
temporary scaffold or bridge. Cells migrate onto this bridge and
begin fusing the ligament ends together. But in ACL injuries, fluid
inside the knee joint dissolves the clot, so a bridge never forms.
Most other ligaments, like the knee's medial collateral ligament (MCL),
are outside the joint and don't have this problem.
"Even though ACL cells are happy to participate in the repair
process, there's no place for them to do it," Murray says. "Our big
finding was recognizing that the cells are fine--they just need a
bridge that they like."
After trying various materials, her team found that the collagen
hydrogel, mixed with platelet-rich blood plasma, was firm enough to
be used as a bridge and wasn't readily dissolved by joint fluid.
In the future, Murray hopes to extend her technique to other
injuries like meniscus and rotator-cuff tears. Her ultimate dream is
cartilage regeneration to repair joints damaged by osteoarthritis.
No one has yet been able to repair cartilage, but Murray has
discovered that even in bad osteoarthritis, cartilage has active,
proliferating cells. She hopes to find another scaffolding material
that would coat the pitted surface of damaged cartilage and recreate
a smooth, nearly friction-free surface--like filling in potholes in
"The cells are trying to find structure, but they just don't have
it," Murray says. "They need a thing to move into; a place to live."
The current study was funded by the National Institute of
Arthritis and Musculoskeletal and Skin Diseases, the National
Football League, the Orthopedic Research and Education Foundation
and the Orthopaedic Foundation of Children's Hospital Boston.