Fig. 1 Intra-operative image of a full-thickness articular cartilage defect of the knee.
Courtesy of Karl F. Almqvist, MD, PhD

AAOS Now

Published 3/1/2010
|
Jennie McKee

Using cells to heal cartilage defects

Chondrocyte implantation may be better than microfracture

Many orthopaedists consider microfracture the “first-line” strategy for treating articular cartilage defects of the knee (Fig. 1). The procedure—in which tiny fractures are made in the subchondral bone to stimulate new cartilage growth—is cost-effective and minimally invasive.

According to Karl Fredrik Almqvist, MD, PhD, characterized chondrocyte implantation (CCI) may be a better option. In CCI, an autologous cartilage cell therapy product optimized for biologic potency is implanted to form stable cartilage tissue.

“We found that patients who underwent cell implantation to treat full-thickness articular cartilage defects of the femoral condyle had better outcomes at 3 years than patients who underwent microfracture,” Dr. Almqvist told the fellows of the American Orthopaedic Society for Sports Medicine at their 2009 annual meeting.

Dr. Almqvist noted that the study he and his colleagues conducted was the first prospective, randomized, and controlled trial on cartilage repair to meet the World Health Organization’s recently released Guidelines for Good Clinical Practice. He stated that the findings in favor of CCI are important because the implanted cells may help produce tissue that is less likely to develop morphologic anomalies and become symptomatic than tissue produced by microfracture. In addition, cell implantation does less harm to subchondral bone.

“Subchondral bone is a major issue when we’re talking about cartilage repair,” said Dr. Almqvist. “Microfracture violates the tidemark and subchondral bone plate and may lead to the development of intralesional osteophytes that can contribute to osteoarthritis.”

Evaluating long-term outcomes
The study involved 118 patients and 12 centers: nine in Belgium and one each in the Netherlands, Germany, and Croatia. Patients, who ranged in age from 18 to 50 years, had a symptomatic single cartilage lesion of the femoral condyle measuring between 1 cm and 5 cm and were randomized to CCI (n = 57) or microfracture (n = 61).

“The two groups were comparable regarding age, gender, body mass index, height, weight, duration since onset, symptom onset (gradual or acute), opposite knee condition, previous knee surgery, and concomitant lesions,” said Dr. Almqvist.

All patients participated in a rehabilitation program that began on the day of surgery and continued at the hospital or at home. Rehabilitation, which was identical for both groups, focused on graft protection and wound control.

Twelve months after surgery, cylindrical full-thickness cartilage biopsy specimens with a diameter of 2 mm were obtained arthroscopically from the center of the repair tissue. Histology assessment scores were determined by two blinded independent histopathologists specializing in cartilage histology.

“Histomorphometric scores demonstrated the superiority of the CCI structural repair at 12 months,” Dr. Almqvist explained. “Clinically, CCI repair was equivalent to microfracture at an average of 12–18 months as measured by the change from baseline in the overall Knee Injury and Osteoarthritis Outcome Score (KOOS) and individual KOOS subdomain scores.”

Finally, researchers conducted a longitudinal analysis to assess clinical benefits at 36 months, using both self-reported and radiographic measures.

Data show benefits of CCI
Significantly greater improvements were found for CCI in a mixed linear model compared to microfracture as measured by all KOOS domains (p-value for the Overall KOOS = 0.0007) except for “Sports” at 36 months.

“For CCI and microfracture groups,” said Dr. Almqvist, “the percentages of treatment responders (improvement of 10 percentage points or more) were 83 percent versus 62 percent on the KOOS scale and 83 percent versus 66 percent on the Visual Analog scale.”

He noted that CCI caused less harm to subchondral bone, as shown by magnetic resonance
imaging.

“We found that bone elevation was significantly more present in the microfracture group than the cell implantation group,” he said, “which may have a potential impact on the clinical outcome.

“The initial superior outcome with CCI at 12 months was substantiated by superior clinical benefit at 36 months compared to microfracture in a mixed linear model analysis with time as a categorical variable,” concluded Dr. Almqvist.

Bottom line

  • Characterized chondrocyte implantation may provide better outcomes than microfracture for full-thickness articular cartilage defects of the knee.
  • Implanted cells may help produce tissue that is less likely to develop morphologic anomalies and become symptomatic than tissue produced by microfracture.
  • Cell implantation does less harm to the subchondral bone.

Dr. Almqvist’s coauthors for “Comparison of characterized chondrocyte implantation versus microfracture in the treatment of symptomatic full-thickness defects of the knee: Results after 3 years” include Daniel B.F. Saris, MD, PhD; Johan Vanlauwe, MD; Jan M.K. Victor, MD; Johan Bellemans, MD; Rene Verdonk, MD, PhD, and Frank P. Luyten, MD, PhD. Dr. Almqvist reported the following disclosures: Johnson & Johnson and Tigenix.

Author disclosure: Jan Victor, MD—Smith & Nephew, Pfizer Praxim. Johan Bellemans, MD—Smith & Nephew, DePuy, A Johnson & Johnson Company; Sanofi-Aventis; Stryker; Synthes; and Zimmer. Rene Verdonk, MD, PhD—Medacta; Orteq; Biomet; EBI; DePuy, A Johnson & Johnson Company; Stryker; Synthes; and Tornier. Frank P. Luyten, MD, PhD—Tigenix; National Institutes of Health; Abbott; Wyeth, UCB; Bristol-Myers Squibb; and Novartis.

“Characterized Chondrocyte Implantation Results in Better Structural Repair When Treating Symptomatic Cartilage Defects of the Knee in a Randomized Controlled Trial Versus Microfracture”

“Treatment of Symptomatic Cartilage Defects of the Knee: Characterized Chondrocyte Implantation Results in Better Clinical Outcome at 36 Months in a Randomized Trial Compared to Microfracture”

Jennie McKee is a staff writer for AAOS Now. She can be reached at mckee@aaos.org