Comparative evaluation of autologous chondrocyte implantation and mosaicplasty: a multicentered randomized clinical trial. Autologous chondrocyte implantation and osteochondral cylinder transplantation in cartilage repair of the knee joint. A prospective, comparative trial. Matrix-induced autologous chondrocyte implantation versus microfracture in the treatment of cartilage defects of the knee: a 2-year randomised study. Autologous chondrocyte implantation compared with microfracture in the knee. A randomized trial. Characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage defects of the knee in a randomized controlled trial versus microfracture. A prospective, randomised comparison of autologous chondrocyte implantation versus mosaicplasty for osteochondral defects in the knee.
To compare the respective performance and effectiveness of autologous chondrocyte implantation (ACI) and mosaicplasty at resurfacing local full-thickness chondral defects of the knee.
                Randomized clinical trial.
                Multicenter trial at orthopedic clinics and university hospitals conducted from 1997 to 2000.
                A population of patients selected according to eligibility criteria of age, traumatic origin of the defect, its localization, size, and gravity, and above all, no previous surgical treatment of the lesion. Forty-seven patients were randomly assigned to ACI or mosaicplasty and subjected to arthroscopic debridement of the lesion at the time of enrollment. They were called for surgery 6 months after the initial debridement.
                Improved knee functionality as assessed by repeated clinical evaluation based on the International Knee Documentation Committee Scale and the Lysholm Knee Scoring Scale.
                Fourteen patients (31.8%) experienced substantial improvement following the initial debridement and, being clinically cured, received no further treatment. Seven patients (15.9%) were lost to follow-up. Among the 23 patients (52.3%) who could effectively be evaluated, a complete recovery (ie, Lysholm Knee Scoring Scale score, 90-100) was observed upon clinical examination in 88% of the mosaicplasty-treated patients and in 68% of the ACI-treated ones (P = 0.093).
                Although the low power of our study prevents definitive conclusions, ACI and mosaicplasty are cartilage repair techniques that are clinically equivalent and similar in performance. The high percentage of spontaneous improvement ((1/3) of the patients) observed after simple debridement calls into question the need for prompt surgical treatment of patients with lesions similar to those included in this clinical trial. Moreover, this finding warrants further investigation, ideally through randomized clinical trials in which patients subjected to debridement alone are compared with patients undergoing reconstructive surgery. Current methods used to restore the joint surface in patients with localized articular cartilage defects include transplantation of an autologous osteochondral cylinder and implantation of autologous chondrocytes. The purpose of this study was to evaluate the clinical and histological outcomes of these two techniques.
                We performed a prospective clinical study to investigate the two-year outcomes in forty patients with an articular cartilage lesion of the femoral condyle who had been randomly treated with either transplantation of an autologous osteochondral cylinder or implantation of autologous chondrocytes. Biopsy specimens from representative patients of both groups were evaluated with histological staining, immunohistochemistry, and scanning electron microscopy.
                According to the postoperative Lysholm score, the recovery after autologous chondrocyte implantation was slower than that after osteochondral transplantation at six months (p < or = 0.015), twelve months (p < or = 0.001), and twenty-four months (p < or = 0.012). On the basis of the Meyers score and the Tegner activity score, the results were equally good with the two methods two years after treatment. Histomorphological evaluation of biopsy specimens within two years after autologous chondrocyte implantation demonstrated a complete, mechanically stable resurfacing of the defect in all patients. The tissue consisted mainly of fibrocartilage, while localized areas of hyaline-like regenerative cartilage could be detected close to the subchondral bone. Although a gap remained at the site of the transplantation in all five biopsy specimens examined as long as two years after osteochondral cylinder transplantation, histomorphological analysis and scanning electron microscopy revealed no differences between the osteochondral transplants and the surrounding original cartilage.
                Both treatments resulted in a decrease in symptoms. However, the improvement provided by the autologous chondrocyte implantation lagged behind that provided by the osteochondral cylinder transplantation. Histologically, the defects treated with autologous chondrocyte implantation were primarily filled with fibrocartilage, whereas the osteochondral cylinder transplants retained their hyaline character, although there was a persistent interface between the transplant and the surrounding original cartilage. Limitations of our study included the small number of patients, the relatively short (two-year) follow-up, and the absence of a control group. Cartilage defects occur in approximately 12% of the population and can result in significant function impairment and reduction in quality of life. Evidence for the variety of surgical treatments available is inconclusive. This study aimed to compare the clinical outcomes of patients with symptomatic cartilage defects treated with matrix-induced autologous chondrocyte implantation (MACI or microfracture (MF). Included patients were >or= 18 and <or= 50 years of age with symptomatic, post-traumatic, single, isolated chondral defects (4-10 cm2) and were randomised to receive MACI or MF. Patients were followed up 8-12, 22-26 and 50-54 weeks post-operatively for efficacy and safety evaluation. Outcome measures were the Tegner, Lysholm and ICRS scores. Sixty patients were included in a randomised study (40 MACI, 20 MF). The difference between baseline and 24 months post-operatively for both treatment groups was significant for the Lysholm, Tegner, patient ICRS and surgeon ICRS scores (all P < 0.0001). However, MACI was significantly more effective over time (24 months versus baseline) than MF according to the Lysholm (P = 0.005), Tegner (P = 0.04), ICRS patient (P = 0.03) and ICRS surgeon (P = 0.02) scores. There were no safety issues related to MACI or MF during the study. MACI is superior to MF in the treatment of articular defects over 2 years. MACI and MF are complementary procedures, depending on the size of the defect and symptom recurrence. The MACI technique represents a significant advance over both first and second generation chondrocyte-based cartilage repair techniques for surgeons, patients, health care institutions and payers in terms of reproducibility, safety, intraoperative time, surgical simplicity and reduced invasiveness. New methods have been used, with promising results, to treat full-thickness cartilage defects. The objective of the present study was to compare autologous chondrocyte implantation with microfracture in a randomized trial. We are not aware of any previous randomized studies comparing these methods.
                Eighty patients without general osteoarthritis who had a single symptomatic cartilage defect on the femoral condyle in a stable knee were treated with autologous chondrocyte implantation or microfracture (forty in each group). We used the International Cartilage Repair Society, Lysholm, Short Form-36 (SF-36), and Tegner forms to collect data. An independent observer performed a follow-up examination at twelve and twenty-four months. Two years postoperatively, arthroscopy with biopsy for histological evaluation was carried out. The histological evaluation was done by a pathologist and a clinical scientist, both of whom were blinded to each patient's treatment.
                In general, there were small differences between the two treatment groups. At two years, both groups had significant clinical improvement. According to the SF-36 physical component score at two years postoperatively, the improvement in the microfracture group was significantly better than that in the autologous chondrocyte implantation group (p = 0.004). Younger and more active patients did better in both groups. There were two failures in the autologous chondrocyte implantation group and one in the microfracture group. No serious complications were reported. Biopsy specimens were obtained from 84% of the patients, and histological evaluation of repair tissues showed no significant differences between the two groups. We did not find any association between the histological quality of the tissue and the clinical outcome according to the scores on the Lysholm or SF-36 form or the visual analog scale.
                Both methods had acceptable short-term clinical results. There was no significant difference in macroscopic or histological results between the two treatment groups and no association between the histological findings and the clinical outcome at the two-year time-point. Level of Evidence: Therapeutic study, Level I-1a (randomized controlled trial [significant difference]). See Instructions to Authors for a complete description of levels of evidence. As the natural healing capacity of damaged articular cartilage is poor, joint surface injuries are a prime target for regenerative medicine. Characterized chondrocyte implantation uses an autologous cartilage cell therapy product that has been optimized for its biological potency to form stable cartilage tissue in vivo.
                To determine whether, in symptomatic cartilage defects of the femoral condyle, structural regeneration with characterized chondrocyte implantation is superior to repair with microfracture.
                Randomized controlled trial; Level of evidence, 1.
                Characterized chondrocyte implantation was compared with microfracture in patients with single grade III to IV symptomatic cartilage defects of the femoral condyles in a multicenter trial. Patients aged 18 to 50 years were randomized to characterized chondrocyte implantation (n = 57) or microfracture (n = 61). Structural repair was blindly assessed in biopsy specimens taken at 1 year using (1) computerized histomorphometry and (2) evaluation of overall histological components of structural repair. Clinical outcome was measured using the self administered Knee injury and Osteoarthritis Outcome Score. Adverse events were recorded throughout the study.
                Characterized chondrocyte implantation resulted in better structural repair, as assessed by histomorphometry (P = .003) and overall histologic evaluation (P = .012). Aspects of structural repair relating to chondrocyte phenotype and tissue structure were superior with characterized chondrocyte implantation. Clinical outcome as measured by the Knee injury and Osteoarthritis Outcome Score at 12 to 18 months after characterized chondrocyte implantation was comparable with microfracture at this stage. Both treatment groups had a similar mean baseline overall Knee injury and Osteoarthritis Outcome Score (56.30 +/- 13.61 and 59.53 +/- 14.95 for microfracture and characterized chondrocyte implantation, respectively), which increased in both groups to 70.56 +/- 12.39 and 72.63 +/- 15.55 at 6 months, 73.26 +/- 14.66 and 73.10 +/- 16.01 at 12 months, and 74.73 +/- 17.01 and 75.04 +/- 14.50 at 18 months, respectively. Both techniques were generally well tolerated; the incidence of adverse events after characterized chondrocyte implantation was not markedly increased compared with that for microfracture.
                One year after treatment, characterized chondrocyte implantation was associated with a tissue regenerate that was superior to that after microfracture. Short-term clinical outcome was similar for both treatments. The superior structural outcome may result in improved long-term clinical benefit with characterized chondrocyte implantation. Long-term follow-up is needed to confirm these findings. Autologous chondrocyte implantation (ACI) and mosaicplasty are both claimed to be successful for the repair of defects of the articular cartilage of the knee but there has been no comparative study of the two methods. A total of 100 patients with a mean age of 31.3 years (16 to 49) and with a symptomatic lesion of the articular cartilage in the knee which was suitable for cartilage repair was randomised to undergo either ACI or mosaicplasty; 58 patients had ACI and 42 mosaicplasty. Most lesions were post-traumatic and the mean size of the defect was 4.66 cm2. The mean duration of symptoms was 7.2 years and the mean number of previous operations, excluding arthroscopy, was 1.5. The mean follow-up was 19 months (12 to 26). Functional assessment using the modified Cincinatti and Stanmore scores and objective clinical assessment showed that 88% had excellent or good results after ACI compared with 69% after mosaicplasty. Arthroscopy at one year demonstrated excellent or good repairs in 82% after ACI and in 34% after mosaicplasty. All five patellar mosaicplasties failed. Our prospective, randomised, clinical trial has shown significant superiority of ACI over mosaicplasty for the repair of articular defects in the knee. The results for ACI are comparable with those in other studies, but those for mosaicplasty suggest that its continued use is of dubious value.
There is insufficient evidence to draw conclusions on the use of ACI for treating full thickness articular cartilage defects in the knee. Further good quality randomised controlled trials with long-term functional outcomes are required.