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Biomedicine

Restoring Damaged Knees

A team of researchers has bioengineered a synthetic scaffold that effectively regenerates tissue in torn knee ligaments.

Carson Palmer, the Cincinnati Bengals’ starting quarterback, was an NFL MVP contender in 2005 until he suffered a tear in his anterior cruciate ligament (ACL), the knee’s main support structure, which is commonly injured in sports. Surgical reconstruction is typically required to repair the ligament, but current methods continue to take significant recovery time, during which a patient may sustain a loss of strength and function. Now, researchers at the University of Virginia have bioengineered a new ACL replacement using a 3-D polymeric fiber braiding process. It’s the first synthetic scaffold design to demonstrate exceptional tissue regeneration and healing, and it could lead to a promising ligament-replacement technology.

“Our goal was to regenerate the ACL using classic design principles from engineering and material that has mechanical properties that mimic the natural ACL,” says Cato Laurencin, the team leader and chairman of the University of Virginia Department of Orthopedic Surgery. His team found that it could utilize its newly developed synthetic polymer system with ACL cells to reconstruct the ligament and produce neoligament tissue. “Any solution that can be devised to speed up the healing and long-term function is hugely important to patients,” says Laurencin.

Current surgical treatment requires an orthopedic surgeon to remove the torn ACL and replace it with a new ligament made either from autograft tissue, which is taken from a patient’s own healthy tissue (usually from a strip of tendon under the kneecap or hamstring), or from allograft tissue, which is taken from a cadaver. To do this, holes are drilled in the places on the tibia and femur where the ACL attaches, and the new ligament is passed through the holes and held in place with screws. Whether using autograft or allograft tissue, the treatment necessitates an extensive healing time ranging from, depending on the severity of the tear, six months to one year, during which the patient might have to wear a brace or use crutches and undergo physical therapy. Palmer spent the final two of almost six months of rehab doing four to six hours of strength and flexibility work a day with a performance coach. This resulted in his being about 80 percent recovered at the start of football training camp.

Several groups have explored ligament-like scaffolds using collagen fibers, silk, and composites, but with limited success. “There just hasn’t been very much successful work done on tissue-engineering ligaments,” says Robert Langer, a professor of chemical and biological engineering at MIT. “This [Laurencin’s team’s work] is a very significant discovery. I haven’t seen anybody do what they are doing with ligaments before.”

The ACL replacement developed by Laurencin’s team uses a clinically proven, FDA-approved biocompatible polymer, polyL-lactide (PLLA), which is frequently used in drug delivery systems, biomedical devices, bone plates, and sutures. Laurencin’s team uses the polymer to stabilize the knee while the scaffold promotes the regeneration of new ligament tissue. The polymer is an absorbable material: its mechanical properties and mass diminish with time and in a manner that permits a favorable biological response.

The design of the synthetic scaffold enables the gradual dissolution of the synthetic material and promotes optimal ligament cell growth for formation of a neoligament, explains Laurencin. Using a process that he refers to as 3-D polymeric fiber braiding, the team of researchers fabricated a 3-D scaffold by braiding the fibers of the PLLA polymer. This method enables cells to efficiently maneuver around the synthetic material and produce collagen fibers and fresh blood vessels much faster than current methods do. Braiding the ligament also gives the structure strength.

To evaluate the newly bioengineered ligaments, Laurencin’s team conducted a study, published in the February 27 issue of Proceedings of the National Academy of Sciences, using rabbit subjects. The study tested two types of the scaffold: one seeded with cells from the rabbits’ ACLs and one consisting of only the synthetic material. The team surgically replaced each rabbit’s torn ACL with one of the two kinds of scaffolds, using the same surgical procedure that would be used on humans. Each scaffold was designed to be slightly smaller than the original rabbit ACL to permit tissue regeneration to take place: tissue growth in the intra-articular, or joint, portion and cell growth in the portion of the scaffold attached to the bone.

The study was performed using 32 rabbits examined at 4 and 12 weeks–the beginning and end of the crucial period of healing. The results for the seeded scaffold were deemed remarkable by Laurencin, who says that within 48 hours of surgery the rabbits were walking around normally. The study reported collagen and cellular infiltration in the implant at 4 weeks, and at 12 weeks the cells at the edge of the scaffold had generated collagen fibers for the formation of a new ligament. In addition to demonstrating faster, short-term recovery time, the neoligament showed sufficient mechanical strength.

“This is the first tissue-engineered matrix for ACL to demonstrate such substantial neoligament formation, in terms of both vascularity and collagen formation,” says Laurencin. “This provides hope for being able to regenerate the ACL in humans and will hopefully pave the way for new treatment paradigms of patients.”

Although Laurencin’s preliminary findings are promising, a few of the rabbits in the seeded group, and almost all of the rabbits in the unseeded group, suffered ruptured ligaments, possibly because rabbits, unlike humans, do not adhere to a physical-therapy schedule, nor are they used to protecting their ligaments. Laurencin plans on continuing to monitor the rabbits and will perform a follow-up study with larger animals and, eventually, humans.

For athletes like Palmer, the system could be the difference between having a great career and a mediocre one.

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