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ABSTRACT: The assessment of cartilage repair has largely been limited to macroscopic observation, magnetic resonance imaging (MRI), or destructive biopsy. The aims of this study were to establish an ovine model of articular cartilage injury repair and to examine the efficacy of nondestructive techniques for assessing cartilage regeneration by matrix-induced autologous chondrocyte implantation (MACI). The development of nondestructive assessment techniques facilitates the monitoring of repair treatments in both experimental animal models and human clinical subjects. Defects (Ø 6 mm) were created on the trochlea and medial femoral condyle of 21 sheep randomized into untreated controls or one of two treatment arms: MACI or collagen-only membrane. Each group was divided into 8-, 10-, and 12-week time points. Repair outcomes were examined using laser scanning confocal arthroscopy (LSCA), MRI, histology, macroscopic ICRS grading, and biomechanical compression analysis. Interobserver analysis of the randomized blinded scoring of LSCA images validated our scoring protocol. Pearson correlation analysis demonstrated the correlation between LSCA, MRI, and ICRS grading. Testing of overall treatment effect independent of time point revealed significant differences between MACI and control groups for all sites and assessment modalities (Asym Sig < 0.05), except condyle histology. Biomechanical analysis suggests that while MACI tissue may resemble native tissue histologically in the early stages of remodeling, the biomechanical properties remain inferior at least in the short term. This study demonstrates the potential of a multisite sheep model of articular cartilage defect repair and its assessment via nondestructive methods.
Journal of Orthopaedic Research 04/2008; 26(3):292-303. · 2.81 Impact Factor
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ABSTRACT: Osteoarthritis (OA) inflicts an enormous burden upon sufferers and healthcare systems worldwide. Continuing efforts to elucidate the aetiology of OA have indicated the need for non-destructive methods of in vivo microstructural assessment of articular cartilage (AC). In this study, we describe the first use of a recently developed laser scanning confocal arthroscope (LSCA) to image the cartilage of a fresh frozen cadaveric knee from a patient with OA.
Using an adaptation of the International Cartilage Repair Society (ICRS) joint mapping protocol, the joint was divided into three discrete regions (femoral condyle, patella and tibial plateau) for grading according to the ICRS (Outerbridge) system. The LSCA was used to generate images from each area within the three regions. Following imaging, the joint was sectioned and histology was performed on the corresponding sites with histological grading (modified-Mankin).
Quantitative results of ICRS, LSCA and histological OA assessment were compared using intraclass correlation (ICC) and Pearson correlation analysis. The LSCA enabled visualisation of chondrocyte morphology and cell density, with classical OA changes such as chondrocyte clustering, surface fibrillation and fissure formation evident. Obvious qualitative similarities between LSCA images and histology were observed, with fair to moderate agreement (P<0.05) demonstrated between modalities.
In this study, we have shown the viability of the LSCA for non-destructive imaging of the microstructure of OA knee cartilage. LSCA technology is potentially a valuable research and clinical tool for the non-destructive assessment of AC microstructure in early to late OA.
Osteoarthritis and Cartilage 12/2007; 15(12):1388-96. · 3.90 Impact Factor
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04/2006; , ISBN: 9780471740360
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ABSTRACT: Confocal laser scanning microscopy (CLSM) is a type of high-resolution fluorescence microscopy that overcomes the limitations of conventional widefield microscopy and facilitates the generation of high-resolution 3D images from relatively thick sections of tissue. As a comparatively non-destructive imaging technique, CLSM facilitates the in situ characterization of tissue microstructure. Images generated by CLSM have been utilized for the study of articular cartilage, bone, muscle, tendon, ligament and menisci by the foremost research groups in the field of orthopaedics including those teams headed by Bush, Errington, Guilak, Hall, Hunziker, Knight, Mow, Poole, Ratcliffe and White. Recent evolutions in techniques and technologies have facilitated a relatively widespread adoption of this imaging modality, with increased "user friendliness" and flexibility. Applications of CLSM also exist in the rapidly advancing field of orthopaedic implants and in the investigation of joint lubrication.
Progress in Histochemistry and Cytochemistry 02/2005; 40(1):1-71. · 4.11 Impact Factor