In vitro determination of biomechanical properties of human articular cartilage in osteoarthritis using multi-parametric MRI.

The objective of this study was to evaluate the correlations between MR parameters and the biomechanical properties of naturally degenerated human articular cartilage. Human cartilage explants from the femoral condyles of patients who underwent total knee replacement were evaluated on a micro-imaging system at 3T. To quantify glycosaminoglycan (GAG) content, delayed gadolinium-enhanced MRI of the cartilage (dGEMRIC) was used. T(2) maps were created by using multi-echo, multi-slice spin echo sequences with six echoes: 15, 30, 45, 60, 75, and 90 ms. Data for apparent diffusion constant (ADC) maps were obtained from pulsed gradient spin echo (PGSE) sequences with five b-values: 10.472, 220.0, 627.0, 452.8, 724.5, and 957.7. MR parameters were correlated with mechanical parameters (instantaneous (I) and equilibrium (Eq) modulus and relaxation time (tau)), and the OA stage of each cartilage specimen was determined by histological evaluation of hematoxylin-eosin stained slices. For some parameters, a high correlation was found: the correlation of T(1Gd) vs Eq (r=0.8095), T(1Gd) vs I/Eq (r=-0.8441) and T(1Gd) vs tau (r=0.8469). The correlation of T(2) and ADC with selected biomechanical parameters was not statistically significant. In conclusion, GAG content measured by dGEMRIC is highly related to the selected biomechanical properties of naturally degenerated articular cartilage. In contrast, T(2) and ADC were unable to estimate these properties. The results of the study imply that some MR parameters can non-invasively predict the biomechanical properties of degenerated articular cartilage.

An in vivo mouse model for human cartilage regeneration.

Cartilage regeneration methods have been examined in various animal models. The major limitation of those studies is the biological difference between human and animal cartilage. We propose an in vivo model for human chondrocytes in a human cartilage defect environment. Human full-thickness (2-4 mm) articular cartilage discs (diameter 10 mm) attached to 3-6 mm subchondral bone, were obtained from human femur heads. Chondral defects (diameter 4 mm) were set within the cartilage disc without violating the subchondral bone. Human chondrocytes were isolated, cultivated for three passages and then suspended at a concentration of 10(7) cells/ml. The defect was completely filled with the cell suspension (approximately 30 microl) and then covered with a thin sheet of human periosteum, fixed with fibrin sealant. Discs were implanted subcutaneously in the backs of nude mice for 5 and 8 weeks. Controls were uncovered discs filled with cell suspension and covered discs without cells. Histological evaluation revealed a gradient of differentiation from the cartilage lateral side to the centre of the defect. A proteoglycan-rich matrix was formed with some chondron-like structures at the border of native cartilage, whereas fibrous tissue was built in the centre of the defect. After 8 weeks the areas of differentiating cells enlarged compared to 5 weeks, indicating the progress of cartilage repair. The control discs without cells or cover showed no chondrogenesis. Interestingly, uncovered discs filled with cells showed comparable areas of differentiating cells at the defect surface but lack of fibrous tissue in the middle. The histological results were supported by MRI measurement.