Background: The Cartilage Regeneration System (CaReS) is a novel matrix-associated autologous chondrocyte implantation (ACI) technique for the treatment of chondral and osteochondral lesions (Outerbridge grades III and IV). For this technology, no expansion of the chondrocytes in a monolayer culture is needed, and a homogeneous cell distribution within the gel is guaranteed.
Purpose: To report a prospective multicenter study of matrix-associated ACI of the knee using a new type I collagen hydrogel (CaReS).
Study Design: Case series; Level of evidence, 4.
Methods: From 2003 to 2008, 116 patients (49 women and 67 men; mean age, 32.5 ± 8.9 years) had CaReS implantation of the knee in 9 different centers. On the basis of the International Cartilage Repair Society (ICRS) Cartilage Injury Evaluation Package 2000, the International Knee Documentation Committee (IKDC) score, pain score (visual analog scale [VAS]), SF-36 score, overall treatment satisfaction and the IKDC functional status were evaluated. Patient follow-up was performed at 3, 6, and 12 months after surgery and annually thereafter. Mean follow-up was 30.2 ± 17.4 months (range, 12-60 months). There were 67 defects of the medial condyle, 14 of the lateral, 22 of the patella/trochlea, and 3 of the tibial plateau, and 10 patients had 2 lesions. The mean defect size was 5.4 ± 2.4 cm2. Thirty percent of the defects were <4 cm2 and 70% were >4 cm2.
Results: The IKDC score improved significantly from 42.4 ± 13.8 preoperatively to 70.5 ± 18.7 (P < .001) at latest follow-up. Global pain level significantly decreased (P < .001) from 6.7 ± 2.2 preoperatively to 3.2 ± 3.1 at latest follow-up. There also was a significant increase of both components of the SF-36 score. The overall treatment satisfaction was judged as very good or good in 88% by the surgeon and 80% by the patient. The IKDC functional knee status was grade I in 23.4%, II in 56.3%, III in 17.2%, and IV in 3.1% of the patients.
Conclusion: Matrix-associated ACI employing the CaReS technology for the treatment of chondral or osteochondral defects of the knee is a safe and clinically effective treatment that yields significant functional improvement and improvement in pain level. However, further investigation is necessary to determine the long-term viability and clinical outcome of this procedure.
Background: Circumscribed cartilage defects are considered as prearthritic lesions and lead to differential intra-articular cytokine expression. Mechanisms of associated pain development and influence of smoking behavior are not yet fully understood in humans.
Purpose: This study aimed to reveal relations between synovial cytokine levels in knees with circumscribed cartilage defects and pain sensation.
Study Design: Descriptive laboratory study.
Methods: In a clinical trial, knee lavage fluids of 42 patients with circumscribed cartilage lesions treated by either microfracturing (n = 19) or by autologous chondrocyte implantation (n = 23) and fluids of 5 healthy control individuals were prospectively collected. Preoperative knee pain was evaluated according to frequency and strength; subjective knee function was assessed using a visual analog scale and the International Knee Documentation Committee (IKDC) score. Synovial concentrations of aggrecan, insulin-like growth factor (IGF)-I, basic fibroblast growth factor (bFGF), interleukin (IL)-1β, bone morphogenetic protein (BMP)-2, and BMP-7 were determined by enzyme-linked immunosorbent assay.
Results: Pain strength showed a highly significant association with intra-articular IGF-1 levels ( = .48, P < .01), but no correlation with synovial concentrations of aggrecan, bFGF, IL-1β, BMP-2, and BMP-7. Although pain strength and frequency demonstrated a statistically significant relationship, no substantial association between pain frequency and any of the examined cytokine levels was found. Intra-articular IGF-1 concentrations significantly correlated with the area of cartilage damage ( = .35, P < .02); the other investigated cytokines failed to show this association. Neither of the determined intra-articular mediators demonstrated statistically significant correlations with subjective knee function or IKDC score. Only intra-articular concentrations of IGF-1 and BMP-2 statistically significantly correlated with age; total protein content was negatively associated with body mass index (P < .05). In smokers, synovial expression of total protein content, IGF-1, and bFGF was significantly diminished compared to nonsmokers (P < .05).
Conclusion: Insulin-like growth factor–I is present in knees with circumscribed cartilage lesions in a size-dependent manner. IGF-1 levels correlated with indicators of pain perception; smoking negatively influenced synovial cytokine expression related to cartilage metabolism, but pain perception was not altered.
Background: Autologous osteochondral mosaicplasty for osteochondritis dissecans of the capitellum is being used increasingly in adolescent patients. Little research has been published on the material properties of living human cartilage of the elbow and knee.
Hypothesis: The cartilage of the osteochondritis dissecans lesion is detected as degenerated by ultrasound. The material properties of the cartilage of the intact part of the elbow are not different from those of the intact knee except in thickness.
Study Design: Descriptive laboratory study.
Methods: The authors studied 10 young male athletes with osteochondritis dissecans of the capitellum who underwent mosaicplasty. An acoustic probe was used for measurement, and the wavelet transform method was used. Three parameters were used: signal intensity (index of cartilage stiffness), signal duration (index of roughness), and signal interval (index of thickness).
Results: The cartilage of the osteochondritis dissecans lesion had lower signal intensity than did the intact part of the capitellum. The cartilage of the radial head opposite the capitellum had significantly lower signal intensity and higher signal duration than did other sites. The signal intensity of the radial head was significantly higher in early-stage patients than in late-stage patients, although the macroscopic view was almost all intact. The signal intensity of the plug was decreased significantly after grafting.
Conclusion: The osteochondritis dissecans lesion had lower signal intensity than did the intact part of the capitellum. Although the macroscopic view looked intact, the radial head cartilage was degenerated as measured acoustically.
Clinical Relevance: Not only the cartilage of the capitellum but the cartilage of the radial head are acoustically degenerated in osteochondritis dissecans patients. Plugs might be damaged in the transplanting procedure, and further follow-up is necessary.
Background
The International Knee Documentation Committee Subjective Knee Form (IKDC SKF) is a patient-reported knee-specific outcome measure that has been shown to be a reliable, valid, and responsive measure for patients with a variety of knee conditions. Further testing is required to compare the reliability and responsiveness of the IKDC SKF to other commonly used patient-reported outcome measures for patients with articular cartilage lesions.
Hypothesis
The IKDC SKF has equal or better levels of reliability and responsiveness than the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), modified Cincinnati Knee Rating System (CKRS), and the Short Form 36 in patients with articular cartilage lesions.
Study Design
Cohort study (diagnosis); Level of evidence, 2.
Methods
Reliability was assessed by administering the 4 patient-reported outcome measures to 17 individuals who had undergone articular cartilage surgery 5 years before participation in this study. Responsiveness was determined by administering the 4 patient-reported outcome measures to 51 individuals with diagnosed focal articular cartilage defects who were scheduled to undergo surgical treatment. In both groups, the outcome measures were administered at baseline and at 6 and 12 months’ follow-up. Participants also provided a global rating of change in comparison to baseline at the 6- and 12-month follow-ups.
Results
Test-retest reliability coefficients were 0.91 and 0.93 for the IKDC SKF at the 6- and 12-month follow-ups, respectively. The effect sizes and standardized response means were large (>0.80) at 6 months after surgery for the WOMAC pain, physical function, and total scores and 12 months after surgery for the IKDC SKF; WOMAC pain, physical function, and total; and CKRS scores. Six months after surgery, significant differences between those who were improved compared with those who were unchanged or worse were found only for the IKDC SKF. Twelve months after surgery, significant differences between the improved and unchanged groups were found for all of the knee-specific patient-reported outcome measures. Finally, the IKDC SKF, WOMAC, and CKRS scores were able to differentiate between individuals who perceived themselves to be improved versus not improved and the minimum clinically important difference for the IKDC SKF was 6.3 at 6 months and 16.7 at 12 months.
Conclusion
The reliability and responsiveness of the IKDC SKF is comparable with other commonly used patient-reported outcome measures for patients with articular cartilage lesions. The IKDC SKF is a suitable alternative to other commonly used knee-specific instruments for measuring symptoms, daily function, and level of symptom-free sports activity in patients undergoing articular cartilage surgery.
Background: First-generation autologous chondrocyte implantation has limitations, and introducing new effective cell sources can improve cartilage repair.
Purpose: This study was conducted to compare the clinical outcomes of patients treated with first-generation autologous chondrocyte implantation to patients treated with autologous bone marrow–derived mesenchymal stem cells (BMSCs).
Study Design: Cohort study; Level of evidence, 3.
Methods: Seventy-two matched (lesion site and age) patients underwent cartilage repair using chondrocytes (n = 36) or BMSCs (n = 36). Clinical outcomes were measured before operation and 3, 6, 9, 12, 18, and 24 months after operation using the International Cartilage Repair Society (ICRS) Cartilage Injury Evaluation Package, which included questions from the Short-Form Health Survey, International Knee Documentation Committee (IKDC) subjective knee evaluation form, Lysholm knee scale, and Tegner activity level scale.
Results: There was significant improvement in the patients’ quality of life (physical and mental components of the Short Form-36 questionnaire included in the ICRS package) after cartilage repair in both groups (autologous chondrocyte implantation and BMSCs). However, there was no difference between the BMSC and the autologous chondrocyte implantation group in terms of clinical outcomes except for Physical Role Functioning, with a greater improvement over time in the BMSC group (P = .044 for interaction effect). The IKDC subjective knee evaluation (P = .861), Lysholm (P = .627), and Tegner (P = .200) scores did not show any significant difference between groups over time. However, in general, men showed significantly better improvements than women. Patients younger than 45 years of age scored significantly better than patients older than 45 years in the autologous chondrocyte implantation group, but age did not make a difference in outcomes in the BMSC group.
Conclusion: Using BMSCs in cartilage repair is as effective as chondrocytes for articular cartilage repair. In addition, it required 1 less knee surgery, reduced costs, and minimized donor-site morbidity.
Background: The medium-term results of autologous chondrocyte implantation (ACI) have shown good to excellent outcomes for the majority of patients. However, no long-term results 10 to 20 years after the surgery have been reported.
Hypothesis: Autologous chondrocyte implantation provides a durable solution to the treatment of full-thickness cartilage lesions of the knee, maintaining good clinical results even 10 to 20 years after implantation.
Study Design: Case series; Level of evidence, 4.
Methods: In this uncontrolled study, questionnaires with the Lysholm, Tegner-Wallgren, Brittberg-Peterson, modified Cincinnati (Noyes), and Knee Injury and Osteoarthritis Outcome Score (KOOS) scores were sent to 341 patients. Preoperative Lysholm, Tegner-Wallgren, and Brittberg-Peterson scores were also retrieved when possible from patients’ files. The patients were asked to grade their status during the past 10 years as better, worse, or unchanged. Finally, they were asked if they would do the operation again.
Results: There were 224 of 341 patients who replied to our posted questionnaires and were assessed. The mean cartilage lesion size was 5.3 cm2. Ten to 20 years after the implantation (mean, 12.8 years), 74% of the patients reported their status as better or the same as the previous years. There were 92% who were satisfied and would have the ACI again. The Lysholm, Tegner-Wallgren, and Brittberg-Peterson scores were improved compared with the preoperative values. The average Lysholm score improved from 60.3 preoperatively to 69.5 postoperatively, the Tegner from 7.2 to 8.2, and the Brittberg-Peterson from 59.4 to 40.9. At the final measurement, the KOOS score was on average 74.8 for pain, 63 for symptoms, 81 for activities of daily living (ADL), 41.5 for sports, and 49.3 for quality of life (QOL). The average Noyes score was 5.4. Patients with bipolar lesions had a worse final outcome than patients with multiple unipolar lesions. The presence of meniscal injuries before ACI or history of bone marrow procedures before the implantation did not appear to affect the final outcomes. The age at the time of the operation or the size of lesion did not seem to correlate with the final outcome.
Conclusion: Autologous chondrocyte implantation has emerged as an effective and durable solution for the treatment of large full-thickness cartilage and osteochondral lesions of the knee joint. Our study suggests that the clinical and functional outcomes remain high even 10 to 20 years after the implantation.
Background: Since the first patient was implanted with autologous cultured chondrocytes more than 20 years ago, new variations of cell therapies for cartilage repair have appeared. Autologous chondrocyte implantation, a first-generation cell therapy, uses suspended autologous cultured chondrocytes in combination with a periosteal patch. Collagen-covered autologous cultured chondrocyte implantation, a second-generation cell therapy, uses suspended cultured chondrocytes with a collagen type I/III membrane. Today’s demand for transarthroscopic procedures has resulted in the development of third-generation cell therapies that deliver autologous cultured chondrocytes using cell carriers or cell-seeded scaffolds.
Purpose: To review the current evidence of the matrix-induced autologous chondrocyte implantation procedure, the most widely used carrier system to date. Also discussed are the characteristics of type I/III collagen membranes, behavior of cells associated with the membrane, surgical technique, rehabilitation, clinical outcomes, and quality of repair tissue.
Study Design: Systematic review.
Methods: Relevant publications were identified by searching Medline from its inception (1949) to December 2007; peer-reviewed publications of preclinical and clinical cell behavior, manufacturing process, surgical technique, and rehabilitation protocols were identified. Preclinical and clinical studies were included if they contained primary data and used a type I/III collagen membrane.
Results: Data from these studies demonstrate that patients treated with matrix-induced autologous chondrocyte implantation have an overall improvement in clinical outcomes. Reduced visual analog scale pain levels (range, 1.7-5.32 points) and improvements in the modified Cincinnati (range, 3.8-34.2 points), Lysholm-Gillquist (range, 23.09-47.6 points), Tegner-Lysholm (range, 1.39-3.9 points), and International Knee Documentation Classification scale (P <.05) were observed. Patients had good-quality (hyaline-like) repair tissue as assessed by arthroscopic evaluation (including International Cartilage Repair Society score), magnetic resonance imaging, and histology, as well as a low incidence of postoperative complications.
Conclusion: The findings suggest that matrix-induced autologous chondrocyte implantation is a promising third-generation cell therapy for the repair of symptomatic, full-thickness articular cartilage defects.
