Treatment of Articular Cartilage Defects of the Knee With Autologous Chondrocyte Implantation

Clinical Results With ACI

The report of the first 23 patients with full-thickness chondral defects, 16 with femoral condyle and 7 with patellar defects, was published in 1994.^[40] The results in 14 of 16 femoral condyle patients (87%) were graded as excellent and good at 39-month follow-up. Second-look arthroscopy and biopsy at an average of 24 months demonstrated formation of new cartilage that was similar to surrounding normal cartilage and had an abundance of type II collagen and metachromatic staining of the matrix. Results were less satisfactory with the treatment of defects of the patella. Although 5 of 7 patients were improved, only 2 were good or excellent. The group with patellar lesions did not undergo realignment procedures.

Encouraged by these promising initial results, the treatment was expanded to include over 500 patients by mid-1997. Reports of the first 100 consecutive patients with average 4-year follow-up (range, 2 to 9 years) presented at the 1997 Annual Meeting of the American Academy of Orthopaedic Surgeons (AAOS) in San Francisco showed consistently good and excellent results in 95% of isolated femoral condyle defects, 89% in femoral OCD, and 75% in patients with femoral condyle defects and ACL reconstruction^[43] ( Table 1 ).

The majority of patients reported on in Dr. Peterson's presentation at the AAOS had failed prior attempts at repair of their chondral defects using either arthroscopic debridement and/or marrow stimulation techniques. The clinical results were evaluated by the Modified Cincinnati, Tegner, Lysholm, VAS (Visual Analog Scale), and Brittberg scales. Each method of evaluation found a statistically significant increase between the preoperative scores and follow-up values. Of 19 biopsy specimens, 14 demonstrated hyaline-like tissue with type II collagen, and 5 were found to have fibrous tissue. There was a correlation of hyaline-like repair tissue with good and excellent clinical results as well as fibrous tissue with fair and poor results. Furthermore, a computerized arthroscopic probe was used on 10 femoral condyle repair sites to measure stiffness. The measurements indicated 3.08 Newtons of control sites of healthy cartilage, 2.77 Newtons for hyaline-like repair tissue, and only 1.23 Newtons in areas of fibrous tissue. The more normal mechanical stiffness of hyaline-like repair tissue appears to also correlate with better clinical outcomes. These findings of histology and mechanical stiffness correlating with clinical outcomes confirm the conclusions and rationale for clinical failure of other methods of cartilage repair, which lead to fibrocartilage or fibrous repair tissue. The more hyaline-like the repair tissue, the better durability and wear characteristics it will exhibit. Dzioba^[1] in 1988 hypothesized that patients would have the best results when the repair tissue more closely resembles the structure of hyaline cartilage, as opposed to the fibrocartilage or fibrous tissue he found in biopsies of patients undergoing arthroscopic drilling.

The recommended indications for this treatment have evolved to include patients with focal full-thickness chondral defects of the femoral condyles, trochlea, and OCD. Relative indications are for patellar, tibial, or multiple defects and are evaluated by surgeons based on the available treatment options for each clinical situation. The prerequisites for this technique require appropriate biomechanical alignment, ligamentous stability, and range of motion. Patients with abnormal biomechanical alignment such as a varus knee may require corrective high tibial osteotomy to alleviate the abnormal force concentration within the involved knee compartment.^[43,44] Patients with patellar tracking abnormalities would require realignment of the extensor mechanism prior to or in conjunction with ACI for a patellar or trochlear defect. ACL-deficient patients likewise would require ligament reconstruction in conjunction with ACI for femoral condyle defects. It should be cautioned, however, that patients with long-standing ligamentous deficiency or biomechanical abnormalities are more likely to have greater degrees of coexisting degenerative changes and therefore may not be suitable candidates for this reason. The same is true with patients who have longstanding changes following a distant total meniscectomy. ACI is not recommended for patients with inflammatory arthritis and moderate-to-severe degenerative joint disease. This procedure is not intended as a treatment for osteoarthritis; rather, the goal of treatment is to prevent a symptomatic cartilage defect from progressing to advanced degenerative arthritis while providing longer-term relief of symptoms and enabling patients to return to physical activities.

ACI has been performed in the United States since 1995. The demographic information, defect description, and clinical parameters have been carefully documented and monitored by a Registry Advisory Board for all patients in the US and Europe undergoing the procedure.^[45] This information, as well as the grading of clinical results using the modified Cincinnati rating scale, provide valuable data on a large group of patients with cartilage defects. The Cartilage Repair Registry periodic report from February 1999 documents the results in 588 patients with 12-month, 220 patients with 24 month, and 40 patients with 36-month follow-up.^[45] This represents 88% capture of the follow-up data of all patients undergoing this procedure outside of Sweden. Some patient data were excluded because they were outside the follow-up window or the patients had additional procedures performed for new injuries or repeat implantation. Based on a modified Cincinnati Knee Rating System scored from 1 to 10 (2=poor, 4=fair, 6=good, 8=very good, and 10=excellent), the 24-month data indicate that clinician evaluation improved from a baseline mean of 3.1 to 6.9 (P < .001) and patient evaluation improved from a baseline of 3.0 to 6.1 (P < .001) at follow-up. These scores improved or remained consistent at 36-month follow-up. On both the clinician and patient evaluations at 24 months, 855 of femoral condyle defect patients were improved. Additionally, the individual parameters of joint line pain, swelling, stiffness, catching, and locking were all significantly improved at each follow-up period. Range of motion was not significantly improved, but was not decreased. In reviewing the 1051 patients undergoing the procedure outside of Sweden through February 1999, a 3.2% adverse event/complication rate related to the implant was observed, resulting in delamination, posttraumatic detachment, periosteal graft tear, or failure of the graft. An additional 2.0% of patients were found to have hypertrophy of the graft, which can be treated arthroscopically and has not been noted to indicate failure of the graft. Arthrofibrosis and adhesions requiring arthroscopic lysis and release were seen in 3.0% of patients. There have been no cases of deep joint infections or rejection of the autologous implant.

The authors' own experience with 80 defects in 65 knees undergoing ACI also appears promising.^[46] The average size of the defects was 5.85 cm², indicating large-sized lesions. The average age was 36.2 years and ranged from 15 to 57 years. The medial femoral condyle was the most frequent site, followed by the lateral femoral condyle, trochlea, and patella. Ten patients had OCD lesions on the femoral condyles. Of 29 patients with more than 2 years follow-up, 89% have shown significant improvement (P < .001) versus baseline and were rated as very good or excellent using the Knee Society and modified Cincinnati rating scales. Patients also demonstrated significant improvement in their sports activity score between 1 and 2 and between 2 and 3 years postoperatively. There has been steady improvement by all evaluated parameters from baseline at 1 year and then also at 2- and 3-year follow-up. This improvement over time appears to be indicative of the progression maturation process of the repair tissue. There has been no deterioration in results in patients with up to 4-year follow-up. Fifty-three of the patients had undergone 84 prior surgeries for cartilage defects, which failed to provide relief of symptoms.

Minas and Nehrer^[47] reported on their early experience with ACI in 50 patients. He noted a gradual time-related improvement in patient-reported symptoms. By 12 months there was a 90% improvement, and by 18 months there was near complete resolution of the preoperative pain. This was believed to be reflective of the repair tissue maturation over time and corresponds to the findings at second-look arthroscopy from an indentable softer tissue at 3 to 6 months to a firm, nonindentable tissue at 18 months. These findings parallel the Swedish experience as well as that of the authors.^[40,43]

Granted, the data from the Cartilage Repair Registry are preliminary, but they represent the results reported by more than 583 surgeons performing the procedure on the steepest portion of the "learning curve" at a variety of hospitals in different communities. As such, the data hold considerable promise. Furthermore, over 71% of these patients had prior surgery that failed to ameliorate their symptoms. Additionally, these results mirror the results found in the Swedish study, and these patients continued to demonstrate good to excellent results up to and over 9 years with an average follow-up of 4 years.

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Cite this: Treatment of Articular Cartilage Defects of the Knee With Autologous Chondrocyte Implantation - Medscape - Mar 20, 2000.