CMI is promising for meniscal repair

The Collagen Meniscus Implant is undergoing tests in multicenter clinical trial. Results are promising; could go before the FDA this year.

Issue: January 2004

In Summary

Collagen Meniscus Implant:

Chondral surfaces seem protected.
No further joint degeneration, arthritis formation.
100-plus patients in United States had one-year relook.

It was once thought that the meniscus was a “meaningless embryologic remnant,” but the groundbreaking work of Kenneth E. DeHaven, MD, and others nearly 30 years ago demonstrated that it could and should be repaired to slow overall degeneration of the knee.

A variety of tools such as sutures and bioabsorbable arrows and screws have proven to be effective, but tissue-engineering scaffolds like the Collagen Meniscus Implant (CMI) could launch a new era in meniscal repair. Extensive clinical studies are underway and a pre-market approval for the CMI could be submitted to the Food and Drug Administration by the end of 2004.

Long-term data

“This has now been implanted in about 850 patients worldwide, so we’re getting quite a good experience with it.”

William G. Rodkey

At the Biennial Congress of the International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine in Auckland, New Zealand, last year, researchers from the Steadman-Hawkins Clinic, in Vail, Colo., presented long-term data on the CMI. The CMI, which is made of purified Type I bovine collagen fibers, is designed to support meniscal tissue regeneration as it is resorbed.

“Based on sequential relooks, the overall significance of the long-term clinical findings is that the new meniscus-like tissue that results from implantation of the Collagen Meniscus Implant continues to survive for nearly six years and is substantially unchanged from the earlier relooks,” William G. Rodkey, DVM, told OrthopedicsToday. J. Richard Steadman, MD, is the principal clinical investigator of the CMI; ReGen Biologics Inc., in Franklin Lakes, N.J., is the developer.

The results were from a phase II feasibility study with eight patients that led to an FDA-approved multicenter clinical trial. At 14 centers, 288 patients were randomized to receive either the CMI or a partial meniscectomy. In addition, about 100 nonrandomized patients were enrolled at 10 sites in Europe and two in Japan.

This is the CMI as it is actually being sutured to the remnant of the host meniscus rim, Size 2-0 polyester sutures were used to secure the implant. The procedure is done arthroscopically.	This is the same patient after one year. The entire CMI has been filled with new tissue, which completely fills the previous defect in the meniscus. Some sutures are still visible.
COURTESY OF WILLIAM G. RODKEY

The eight patients from the feasibility study underwent relook arthroscopy and biopsy at six and 12 months and a subsequent relook exam at an average of 5.8 years, Rodkey said. “The chondral surfaces appear to be protected by this new meniscus tissue because there hasn’t been any further joint degeneration or arthritis formation on the medial side where the Collagen Meniscus Implant was placed.”

Scores improved

This goat knee meniscus is used as a model to achieve tissue engineering of the human knee meniscus.

COURTESY OF KYRIACOS ATHANASIOU

The average Lysholm scores improved from 75 to 88 at five-or six-year follow-up and average Tegner Activity Scores improved from three to six. The initial relook revealed that 76% of the defect was filled, and those patients continued to have 70% of the defect filled five to six years later. More than 100 patients in the U.S. trial have undergone one-year relook and biopsy.

The gross appearance and shape of the regenerated tissue was generally similar to native meniscus, with solid interface to the host meniscus rim in the feasibility study. Histologically, the implant was progressively invaded and replaced by cells similar to meniscofibrochondrocytes with production of new matrix.

No serious complications were attributed to the CMI and patients routinely returned to daily activities by three months; most were fully active by six months. Testing failed to detect any increase in antibodies to the collagen in the implant.

The device is approved for use in Europe, Australia and Chile, and the regulatory process is ongoing in Japan. “This has now been implanted in about 850 patients worldwide, so we’re getting quite a good experience with it,” Rodkey said.

While they are not yet ready for human clinical trials, there are other biologic methods of meniscal repair being investigated. Kyriacos Athanasiou, PhD, of Rice University, has received funding from the National Institutes of Health to investigate the feasibility of tissue engineering a meniscus in vitro and then testing it in a rabbit model.

“By having an in vitro approach, we can control the factors, the mechanical stimulation, the cells and the nutrients that the cells need to get,” he said. “We believe that by controlling all those variables, the cell-seeded scaffold will eventually give birth to a fully tissue-engineered meniscus construct.”

Another approach was outlined in Arthroscopy: The Journal of Arthroscopic and Related Surgery that evaluated the use of porcine small intestine submucosa (SIS) as a scaffold for meniscal tissue regeneration. Researchers led by Jonathan A. Gastel, MD, of Brown University, created defects in the lateral menisci of 12 mature New Zealand White rabbits.

The defects were repaired with a similarly shaped and sized wedge of SIS that was sutured into place. At 24 weeks, the graft was nearly totally replaced by host tissue and the meniscus defect was grossly healed.

Its shape, contour, consistency and color looked virtually normal. Histologically, the healing tissue showed infiltration of what appeared to be meniscal fibrochondrocytes and connective tissue resembling the host connective tissue.