Matrix-Applied Characterized Autologous Cultured Chondrocytes Versus Microfracture: Two-Year Follow-up of a Prospective Randomized Trial.

BACKGROUND: Randomized controlled trials studying the efficacy and safety of matrix-applied characterized autologous cultured chondrocytes (MACI) versus microfracture (MFX) for treating cartilage defects are limited. PURPOSE: To compare the clinical efficacy and safety of MACI versus MFX in the treatment of patients with symptomatic cartilage defects of the knee. STUDY DESIGN: Randomized controlled clinical trial; Level of evidence, 1. METHODS: Patients enrolled in the SUMMIT (Demonstrate the Superiority of MACI implant to Microfracture Treatment) trial had ≥1 symptomatic focal cartilage defect (Outerbridge grade III or IV; ≥3 cm(2)) of the femoral condyles or trochlea, with a baseline Knee Injury and Osteoarthritis Outcome Score (KOOS) pain value <55. The co-primary efficacy endpoint was the change in the KOOS pain and function subscores from baseline to 2 years. Histological evaluation and magnetic resonance imaging (MRI) assessments of structural repair tissue, treatment failure, the remaining 3 KOOS subscales, and safety were also assessed. RESULTS: Of the 144 patients treated, 137 (95%) completed the 2-year assessment. Patients had a mean age of 33.8 years and a mean lesion size of 4.8 cm(2). The mean KOOS pain and function subscores from baseline to 2 years were significantly more improved with MACI than with MFX (pain: MACI, 37.0 to 82.5 vs MFX, 35.5 to 70.9; function: MACI, 14.9 to 60.9 vs MFX, 12.6 to 48.7; P = .001). A significant improvement in scores was also observed on the KOOS subscales of activities of daily living (MACI, 43.5 to 87.2 vs MFX, 42.6 to 75.8; P < .001), knee-related quality of life (MACI, 18.8 to 56.2 vs MFX, 17.2 to 47.3; P = .029), and other symptoms (MACI, 48.3 to 83.7 vs MFX, 44.4 to 72.2; P < .001) for patients treated with MACI compared with MFX. Repair tissue quality was good as assessed by histology/MRI, but no difference was shown between treatments. A low number of treatment failures (nonresponders: MACI, 12.5% vs MFX, 31.9%; P = .016) and no unexpected safety findings were reported. CONCLUSION: The treatment of symptomatic cartilage knee defects ≥3 cm(2) in size using MACI was clinically and statistically significantly better than with MFX, with similar structural repair tissue and safety, in this heterogeneous patient population. Moreover, MACI offers a more efficacious alternative than MFX with a similar safety profile for the treatment of symptomatic articular cartilage defects of the knee.

Cruciate ligaments in proximal femoral focal deficiency: arthroscopic assessment.

BACKGROUND: Because there is limited information concerning the cruciate ligaments in proximal femoral focal deficiency, knee arthroscopy was used to identify the changes of cruciate ligaments and their relation to the different types of this deficiency. METHODS: Knee arthroscopy was performed in 21 consecutive patients with deficiency types III, IV, VII-IX using the Pappas classification. A new classification of the knee was created. It contains types I, II, III according to the findings of the anterior cruciate ligament (ACL) (type I: normal, type II: hypoplasia, type III: aplasia) and 3 subtypes A, B, C according to the findings of the posterior cruciate ligament (PCL) (type A: normal, type B: hypoplasia, type C: aplasia), respectively. Instrumented and radiologic drawer testing was provided additionally in 2010. RESULTS: The changes of the cruciate ligaments were found in all but 1 patient. Type I was found in only 2 patients. In 1, both cruciate ligaments were intact (type IA). In the other patient, the ACL was intact, but the PCL was absent (type IC). Hypoplastic ACLs (type II) were found in 4 patients, namely in 3 patients with normal PCLs (type IIA), whereas in 1 patient the PCL was absent (type IIC). In the majority of patients, the ACLs completely failed (type III, 15 patients). Absence of both cruciate ligaments was found in 8 patients (type IIIC). PCLs were intact in 4 patients (IIIA) or were hypoplastic in 3 patients (IIIB), respectively. Instrumental drawer testing was not reliable in patients of our group. Radiologic testing showed a posterior shift of the tibia in the majority of patients on the affected side. Anterior and posterior drawer tests were increased in a majority of patients, but did not directly correlate to the presence/absence of cruciate ligaments. CONCLUSIONS: Variable changes of the cruciate ligaments were found in all but 1 patient with proximal femoral focal deficiency. These changes were not related to the type of Pappas classification. Despite the lower clinical relevance of the changes in majority of patients, imaging of cruciate ligaments is recommend before lengthening of the extremity to avoid dislocation of the knee. LEVEL OF EVIDENCE: I - Testing of previously developed diagnostic criteria in series of consecutive patients.

Distribution of chondrocytes containing alpha-smooth muscle actin in human normal, osteoarthrotic, and transplanted articular cartilage.

The aim of our study was to evaluate the occurrence of chondrocytes containing alpha-smooth muscle actin in human normal and diseased cartilage. Immunohistochemistry using monoclonal antibodies for alpha-smooth actin, muscle-specific actin, S-100 protein, CD 34, and desmin was performed on samples of human articular cartilage obtained at autopsy following sudden death, during total hip and knee replacement for osteoarthritis, or after femoral neck fracture in patients without symptoms of osteoarthritis. Moreover, the layers of residual cartilage from chondral posttraumatic defects obtained during preoperative arthroscopy and of newly formed cartilage after autologous-chondrocyte transplantation (Hyalograft C) obtained during second-look arthroscopy were also examined by immunohistochemistry and RT PCR. Our study showed that a significant percentage of articular chondrocytes express alpha-smooth muscle actin in healthy, diseased, and regenerated articular cartilage. Alpha-actin positive chondrocytes (18%) were observed predominantly in the upper zone of normal articular cartilage. By contrast, only approximately 10% of cartilage cells in the deep region stained for this contractile actin isoform. Actin-positive chondrocytes (myochondrocytes) are formed predominantly in response to injury to the osteoarthrotic cartilage, at sites of defective healing, and in newly formed cartilage after autologous chondrocyte transplantation. Fibrocartilage is present in some of these conditions, and it is known that this tissue contains chondrocytes with actin. The presence of myochondrocytes in the surface layer of normal articular cartilage indicates that this region probably plays an important role in maintaining cartilage integrity. Myochondrocytes may utilize the contractile actin isoform in manipulating the extracellular matrix of articular cartilage. It is also possible that actin-containing chondrocytes have a higher potential for regeneration in contrast to chondrocytes that do not contain this contractile material in their cytoplasm.