Characterized Chondrocyte Implantation Research Articles

Surgical Techniques for Knee Cartilage Repair: An Updated Large-Scale Systematic Review and Network Meta-analysis of Randomized Controlled Trials

The aim of this study was to investigate the most appropriate surgical interventions for patients with knee articular cartilage defects from the level I randomized clinical trials. We searched five databases for level I randomized clinical trials. Treatments were compared if reported in more than one study using network meta-analysis to boost the number of included studies per comparison. We studied 21 articles that included 891 patients. Traumatic lesion was the most common cause in the included patients. There were significantly higher failure rates in the microfracture (MF) group compared to autologous chondrocyte implantation (ACI) group at 10-year follow-up. Moreover, osteochondral autograft transplantation (OAT) showed significantly more excellent or good results at > 3-year follow-up compared to MF, whereas MF showed significantly more poor results versus ACI and matrix-induced autologous chondrocyte implantation (MACI). Furthermore, OAT showed significantly more poor results than MACI at 1-year follow-up. Similarly, patients who underwent OAT had higher return-to-activity rates than those with MF. It is noteworthy that the Knee injury and Osteoarthritis Outcome Score was higher in patients who underwent characterized chondrocyte implantation or MACI compared to MF. Finally, there were no significant differences among the various interventions regarding reintervention, biopsy types or adverse events. According to the P scores for interventions ranking, there was a disagreement concerning the best intervention; however, MF was always ranked as the last. Cartilage repair techniques, rather than MF, provide higher quality repair of tissue and have lower failure and higher return-to-activity rates. Moreover, OAT had significantly more excellent or good results compared to MF, whereas MF had significantly more poor results than ACI and MACI. Future studies need to have longer follow-up periods and more representative populations to investigate the efficacy and safety of these interventions. Level I: meta-analysis of Level I studies.

Characterized Chondrocyte Implantation in the Patellofemoral Joint

Background: Autologous chondrocyte implantation (ACI) is an accepted treatment option for selected condylar cartilage defects in the knee. Results for patellofemoral chondral defects have been less favorable. Hypothesis: Autologous chondrocyte implantation with characterized chondrocytes will result in clinically relevant improvement in patellofemoral lesions. Study Design: Case series; Level of evidence, 4. Methods: Patients with symptomatic patellofemoral full-thickness cartilage lesions were treated with ACI using characterized chondrocytes (ChondroCelect) covered with a collagen type I membrane. Clinical outcome was assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS) and a visual analog scale (VAS) for pain. Responders were defined using 5 categories (≥10 points and ≥20%, 30%, 50%, 70%) based on the KOOS and VAS. Treatment failure was defined as partial loosening of more than 20% of the graft with subsequent procedures to the subchondral bone. Results: Thirty-eight patients, with a mean defect size of 4.89 cm2 (range, 1.5-11 cm2), were treated for a patellar defect (n = 28), trochlear defect (n = 7), or a kissing lesion (trochlea and patella; n = 3). The minimum follow-up period was 24 months (mean, 37 months; range, 24-72 months). Treated patients showed statistically significant improvements in the KOOS (at 12, 18, 24, 36, and 48 months) and VAS (at the same time points) compared with pretreatment for each time point. Responder analysis identified approximately 84% of patients with a clinically relevant improvement greater than 10 points at 3 years. Treatment failure was observed in 5 patients. The most commonly reported adverse events were joint crepitation (n = 18) and arthrofibrosis (n = 7). No relationship could be found between clinical outcome and anatomic characteristics of the patellofemoral joint, lesion size and site, time since onset, or age. Nine patients required additional surgery: 6 because of persistent symptoms and 3 for hardware removal. Conclusion: Characterized chondrocyte implantation resulted in statistically significant and clinically relevant improvement over time. These results add to the evidence demonstrating that ACI is a valuable cartilage repair technique for patellofemoral lesions.

Second generation characterized chondrocyte implantation for the treatment of cartilage lesions in the knee

Second generation characterized chondrocyte implantation for the treatment of cartilage lesions in the knee

Clinical Outcomes of Characterized Chondrocyte Implantation.

Objective:To assess the clinical outcome of patients treated with autologous chondrocyte implantation using ChondroCelect in daily practice.Methods:The study is a cross-sectional analysis of an open-label, noninterventional cohort. The setting was a compassionate use program, involving 43 orthopaedic centers in 7 European countries. The participants were patients treated with ChondroCelect between October 13, 2004 and July 2, 2008. The measurements used were Clinical Global Impression–Improvement and –Efficacy and solicited adverse event reports.Results:Safety data were collected from 334 patients (90.3%), and effectiveness data were from 282 (76.2%) of the 370 patients treated. Mean age at baseline was 33.6 years (range, 12-57 years), 57% were male, and mean body mass index was 25 kg/m2. Mean follow-up was 2.2 years (range, 0.4-4.1 years). A femoral condyle lesion was reported in 66% (288/379) and a patellar lesion in 19% (84/379). Mean lesion size was 3.5 cm2; a collagen membrane was used in 92.4% (328/355). A therapeutic effect was reported in 89% (234/264) of patients overall and in 87% (40/46) of patellar lesion patients. Rates of much or very much improved patients were similar in patients with short- (<18 months: 71% [115/163]) and long-term follow-up (>18 months: 68% [70/103]) (P = 0.68) and were independent of lesion size (>4 cm2: 75.5% [37/49]; ≤4 cm2: 67.7% [111/164]) (P = 0.38). Adverse events were similar to those reported in the randomized trial with the same product, with more arthrofibrosis, more reduced joint mobility, and more crepitations reported in patellar lesions. Overall, less cartilage hypertrophy was noted, probably due to the use of a biological membrane cover.Conclusions:Implantation of ChondroCelect appeared to result in a positive benefit/risk ratio when used in an unselected heterogenous population, irrespective of the follow-up period, lesion size, and type of lesion treated.

Short-term outcome of the second generation characterized chondrocyte implantation for the treatment of cartilage lesions in the knee

To evaluate short-term clinical and MRI outcome of the second generation characterized chondrocyte implantation (CCI) for the treatment of cartilage defects in the knee. Thirty-two patients aged 15-51 years with single International Cartilage Repair Society (ICRS) grade III/IV symptomatic cartilage defects of different locations in the knee were treated with CCI using a synthetic collagen I/III membrane to cover the defect. Clinical outcome was measured over 36 months by the Knee injury and Osteoarthritis Outcome Score (KOOS) and Visual Analogue Scale (VAS) for pain. Serial magnetic resonance imaging (MRI) scans of 22 patients were scored using the original and modified Magnetic resonance Observation of Cartilage Repair Tissue (MOCART) system. The patients included in this study showed a significant gradual clinical improvement after CCI. The MRI findings of this pilot study were considered to be promising. No signs of deterioration were observed. A complete or hypertrophic filling was observed in 76.5% of the cases at 24 months of follow-up. No preventive effect of an avital membrane on the occurrence of hypertrophic repair tissue was observed on MRI. Three failures were observed among the 32 patients until now (9.4%). This investigation provided useful information on the efficacy of this treatment. The short-term clinical and MRI outcome are promising. Large-scale and long-term trials are mandatory to confirm the results and the reliability of this procedure. IV.

Five-Year Outcome of Characterized Chondrocyte Implantation Versus Microfracture for Symptomatic Cartilage Defects of the Knee

Background: Characterized chondrocyte implantation (CCI) results in significantly better early structural tissue regeneration than microfracture (MF), and CCI has a midterm clinical benefit over microfracture. Purpose: This study was undertaken to evaluate the 5-year clinical outcome of CCI in a randomized comparison with MF for the treatment of symptomatic cartilage defects of the femoral condyles of the knee. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Participants aged 18 to 50 years with a symptomatic isolated International Cartilage Repair Society (ICRS) grade III or IV cartilage lesion of the femoral condyles between 1 and 5 cm2 were randomized to either CCI or MF. Clinical outcomes were measured up to 60 months after surgery using the Knee Injury and Osteoarthritis Outcome Score (KOOS). The main outcome parameter was change from baseline in overall KOOS (oKOOS). Adverse events were monitored. Results: Fifty-one participants were treated with CCI and 61 with MF. On average, clinical benefit was maintained through the 60-month follow-up period. The average change from baseline in oKOOS was not different between both groups (least squares [LS] mean ± standard error [SE] 18.84 ± 3.58 for CCI vs 13.21 ± 5.63 for MF; P = .116). Treatment failures were comparable (n = 7 in CCI vs n = 10 in MF), although MF failures tended to occur earlier. Subgroup analysis revealed that CCI resulted in better outcome in participants with time since symptom onset of less than 3 years, which was statistically significant and clinically relevant (change in oKOOS <3 years mean ± SE 25.96 ± 3.45 for CCI vs 15.28 ± 3.17 for MF; P = .026 vs oKOOS >3 years mean ± SE 13.09 ± 4.78 for CCI vs 17.02 ± 4.50 for MF, P = .554). Other subgroup analyses such as age (cutoff 35 years) did not show a difference. Female patients showed more failures irrespective of treatment. Conclusion: At 5 years after treatment, clinical outcomes for CCI and MF were comparable. In the early treatment group, CCI obtained statistically significant and clinically relevant better results than MF. Delayed treatment resulted in less predictable outcomes for CCI. These results provide strong evidence that time since onset of symptoms is an essential variable that should be taken into account in future treatment algorithms for cartilage repair of the knee.

Physical Activity Levels after Characterized Chondrocyte Implantation versus Microfracture in the Knee and the Relationship to Objective Functional Outcome with 2-year Follow-up

Background Characterized chondrocyte implantation results in superior structural repair compared with microfracture, but may be associated with a slower recovery of physical activity levels due to the arthrotomy. Hypotheses Our hypotheses were that (1) microfracture results in increased activity levels over 2 years after surgery compared with characterized chondrocyte implantation, (2) patients with high preinjury activity levels have a better functional outcome, and (3) high levels of low-load activities after surgery improve functional outcome. Study Design Cohort study; Level of evidence, 2. Methods Sixty-seven patients with local cartilage defects (mean size, 2.4 cm2; standard deviation, 1.5 cm2) of the femoral condyle underwent characterized chondrocyte implantation (n = 33) or microfracture (n = 34), followed by an identical rehabilitation protocol. Activity levels (assessed using the Activity Rating Scale) and functional outcome were determined at baseline, and 1 and 2 years after surgery. Functional outcome was based on the pooled symmetry index (derived from isokinetic knee extension strength and 3 one-legged hop tests). Patients’ participation in low-load activities during the first 3 months after surgery was assessed using rehabilitation data. Mixed linear model analyses and Wilcoxon rank sum tests were used. Results Activity levels in patients treated with characterized chondrocyte implantation and microfracture were comparable at 1 and 2 years after surgery. Preinjury activity levels showed no relationship to functional outcome. Lack of postoperative low-load activities resulted in a significantly worse functional outcome (mean pooled symmetry index 78.2%) compared with high levels of postoperative surgery low-load activities (mean pooled symmetry index 92.4%). Conclusion Despite differences between the characterized chondrocyte implantation and microfracture procedures, patients’ activity levels were comparable at 2 years after surgery. Lack of low-load activities after surgery adversely affected functional outcome.

Treatment of Symptomatic Cartilage Defects of the Knee

Background Damaged articular cartilage has limited capacity for self-repair. Autologous chondrocyte implantation using a characterized cell therapy product results in significantly better early structural repair as compared with microfracture in patients with symptomatic joint surface defects of the femoral condyles of the knee. Purpose To evaluate clinical outcome at 36 months after characterized chondrocyte implantation (CCI) versus microfracture (MF). Study Design Randomized controlled trial; Level of evidence, 1. Methods Patients aged 18 to 50 years with single International Cartilage Repair Society (ICRS) grade III/IV symptomatic cartilage defects of the femoral condyles were randomized to CCI (n = 57) or MF (n = 61). Clinical outcome was measured over 36 months by the Knee injury and Osteoarthritis Outcome Score (KOOS). Serial magnetic resonance imaging (MRI) scans were scored using the Magnetic resonance Observation of Cartilage Repair Tissue (MOCART) system and 9 additional items. Gene expression profile scores associated with ectopic cartilage formation were determined by RT-PCR. Results Baseline mean overall KOOS (±SE) was comparable between the CCI and MF groups (56.30 ± 1.91 vs 59.46 ± 1.98, respectively). Mean improvement (±SE) from baseline to 36 months in overall KOOS was greater in the CCI group than the MF group (21.25 ± 3.60 vs 15.83 ± 3.48, respectively), while in a mixed linear model analysis with time as a categorical variable, significant differences favoring CCI were shown in overall KOOS (P = .048) and the subdomains of Pain (P = .044) and QoL (P = .036). More CCI- than MF-treated patients were treatment responders (83% vs 62%, respectively). In patients with symptom onset of <2 years, the mean improvement (±SE) from baseline to 36 months in overall KOOS was greater with CCI than MF (24.98 ± 4.34 vs 16.50 ± 3.99, respectively) and even greater in patients with symptom onset of <3 years (26.08 ± 4.10 vs 17.09 ± 3.77, respectively). Characterized chondrocyte implantation patients with high (>2) versus low (<2) gene profile scores showed greater improvement from baseline in mean overall KOOS (±SE) at 36 months (28.91 ± 5.69 vs 18.18 ± 5.08, respectively). Subchondral bone reaction significantly worsened over time with MF compared with CCI (P < .05). Conclusion Characterized chondrocyte implantation for the treatment of articular cartilage defects of the femoral condyles of the knee results in significantly better clinical outcome at 36 months in a randomized trial compared with MF. Time to treatment and chondrocyte quality were shown to affect outcome.

Characterized Chondrocyte Implantation Results in Better Structural Repair when Treating Symptomatic Cartilage Defects of the Knee in a Randomized Controlled Trial versus Microfracture

Background 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. Purpose To determine whether, in symptomatic cartilage defects of the femoral condyle, structural regeneration with characterized chondrocyte implantation is superior to repair with microfracture. Study Design Randomized controlled trial; Level of evidence, 1. Methods 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. Results 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. Conclusion 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.

29.4 Comparison of structural repair following characterized chondrocyte implantation or microfracture for the treatment of symptomatic cartilage defects of the knee

29.4 Comparison of structural repair following characterized chondrocyte implantation or microfracture for the treatment of symptomatic cartilage defects of the knee

6.3 Evaluating knee function in patients treated with characterized chondrocyte implantation and microfracture, following an identical, standardized rehab protocol.

6.3 Evaluating knee function in patients treated with characterized chondrocyte implantation and microfracture, following an identical, standardized rehab protocol.

6.6 Implementation of rehabilitation exercises for patients treated with characterized chondrocyte implantation and microfracture.

6.6 Implementation of rehabilitation exercises for patients treated with characterized chondrocyte implantation and microfracture.

P59 Magnetic resonance imaging of cartilage repair in the knee: benefits of characterized chondrocyte implantation compared to microfracture.

P59 Magnetic resonance imaging of cartilage repair in the knee: benefits of characterized chondrocyte implantation compared to microfracture.

P48 Characterized chondrocyte implantation has a similar safety profile to microfracture forthe treatment of symptomatic cartilage defects of the knee

P48 Characterized chondrocyte implantation has a similar safety profile to microfracture forthe treatment of symptomatic cartilage defects of the knee

P47 Short-term clinical outcome following characterized chondrocyte implantation versus microfracture for symptomatic cartilage lesions of the knee.

P47 Short-term clinical outcome following characterized chondrocyte implantation versus microfracture for symptomatic cartilage lesions of the knee.