Depth-wise progression of osteoarthritis in human articular cartilage: investigation of composition, structure and biomechanics

SummaryObjectiveOsteoarthritis (OA) is characterized by the changes in structure and composition of articular cartilage. However, it is not fully known, what is the depth-wise change in two major components of the cartilage solid matrix, i.e., collagen and proteoglycans (PGs), during OA progression. Further, it is unknown how the depth-wise changes affect local tissue strains during compression. Our aim was to address these issues.MethodsData from the previous microscopic and biochemical measurements of the collagen content, distribution and orientation, PG content and distribution, water content and histological grade of normal and degenerated human patellar articular cartilage (n=73) were reanalyzed in a depth-wise manner. Using this information, a composition-based finite element (FE) model was used to estimate tissue function solely based on its composition and structure.ResultsThe orientation angle of collagen fibrils in the superficial zone of cartilage was significantly less parallel to the surface (P<0.05) in samples with early degeneration than in healthy samples. Similarly, PG content was reduced in the superficial zone in early OA (P<0.05). However, collagen content decreased significantly only at the advanced stage of OA (P<0.05). The composition-based FE model showed that under a constant stress, local tissue strains increased as OA progressed.ConclusionFor the first time, depth-wise point-by-point statistical comparisons of structure and composition of human articular cartilage were conducted. The present results indicated that early OA is primarily characterized by the changes in collagen orientation and PG content in the superficial zone, while collagen content does not change until OA has progressed to its late stage. Our simulation results suggest that impact loads in OA joint could create a risk for tissue failure and cell death

T2 relaxation time mapping reveals age- and species-related diversity of collagen network architecture in articular cartilage

SummaryObjectiveThe magnetic resonance imaging (MRI) parameter T2 relaxation time has been shown to be sensitive to the collagen network architecture of articular cartilage. The aim of the study was to investigate the agreement of T2 relaxation time mapping and polarized light microscopy (PLM) for the determination of histological properties (i.e., zone and fibril organization) of articular cartilage.MethodsT2 relaxation time was determined at 9.4T field strength in healthy adult human, juvenile bovine and juvenile porcine patellar cartilage, and related to collagen anisotropy and fibril angle as measured by quantitative PLM.ResultsBoth T2 and PLM revealed a mutually consistent but varying number of collagen-associated laminae (3, 3–5 or 3–7 laminae in human, porcine and bovine cartilage, respectively). Up to 44% of the depth-wise variation in T2 was accounted for by the changing anisotropy of collagen fibrils, confirming that T2 contrast of articular cartilage is strongly affected by the collagen fibril anisotropy. A good correspondence was observed between the thickness of T2-laminae and collagenous zones as determined from PLM anisotropy measurements (r=0.91, r=0.95 and r=0.91 for human, bovine and porcine specimens, respectively).ConclusionsAccording to the present results, T2 mapping is capable of detecting histological differences in cartilage collagen architecture among species, likely to be strongly related to the differences in maturation of the tissue. This diversity in the MRI appearance of healthy articular cartilage should also be recognized when using juvenile animal tissue as a model for mature human cartilage in experimental studies

Repair of osteochondral defects with recombinant human type II collagen gel and autologous chondrocytes in rabbit

SummaryObjectiveRecombinant human type II collagen (rhCII) gels combined with autologous chondrocytes were tested as a scaffold for cartilage repair in rabbits in vivo.MethodAutologous chondrocytes were harvested, expanded and combined with rhCII-gel and further pre-cultivated for 2 weeks prior to transplantation into a 4 mm diameter lesion created into the rabbit's femoral trochlea (n = 8). Rabbits with similar untreated lesions (n = 7) served as a control group.ResultsSix months after the transplantation the repair tissue in both groups filled the lesion site, but in the rhCII-repair the filling was more complete. Both repair groups also had high proteoglycan and type II collagen contents, except in the fibrous superficial layer. However, the integration to the adjacent cartilage was incomplete. The O'Driscoll grading showed no significant differences between the rhCII-repair and spontaneous repair, both representing lower quality than intact cartilage. In the repair tissues the collagen fibers were abnormally organized and oriented. No dramatic changes were detected in the subchondral bone structure. The repair cartilage was mechanically softer than the intact tissue. Spontaneously repaired tissue showed lower values of equilibrium and dynamic modulus than the rhCII-repair. However, the differences in the mechanical properties between all three groups were insignificant.ConclusionWhen rhCII was used to repair cartilage defects, the repair quality was histologically incomplete, but still the rhCII-repairs showed moderate mechanical characteristics and a slight improvement over those in spontaneous repair. Therefore, further studies using rhCII for cartilage repair with emphasis on improving integration and surface protection are required

Регіональні й глобальні наслідки незалежності Косово

У статті розглянуто регіональні й міжнародні аспекти проголошення незалежності Косово. Проаналізовано конфліктні аспекти косовської проблеми у регіональному й глобальному контекстах.В статье рассматриваются региональные и международные аспекты провозглашения независимости Косово. Проанализировано конфликтные аспекты косовской проблемы в региональном и глобальном контекстах.The article presents the regional and international aspects of Kosovo Independents. Special attention is to the conflict of Kosovo in the regional and global context

Estimation of articular cartilage properties using multivariate analysis of optical coherence tomography signal

SummaryObjectiveThe aim was to investigate the applicability of multivariate analysis of optical coherence tomography (OCT) information for determining structural integrity, composition and mechanical properties of articular cartilage.DesignEquine osteochondral samples (N = 65) were imaged with OCT, and their total attenuation and backscattering coefficients (μt and μb) were measured. Subsequently, the Mankin score, optical density (OD) describing the fixed charge density, light absorbance in amide I region (Aamide), collagen orientation, permeability, fibril network modulus (Ef) and non-fibrillar matrix modulus (Em) of the samples were determined. Partial least squares (PLS) regression model was calculated to predict tissue properties from the OCT signals of the samples.ResultsSignificant correlations between the measured and predicted mean collagen orientation (R2 = 0.75, P < 0.0001), permeability (R2 = 0.74, P < 0.0001), mean OD (R2 = 0.73, P < 0.0001), Mankin scores (R2 = 0.70, P < 0.0001), Em (R2 = 0.50, P < 0.0001), Ef (R2 = 0.42, P < 0.0001), and Aamide (R2 = 0.43, P < 0.0001) were obtained. Significant correlation was also found between μb and Ef (ρ = 0.280, P = 0.03), but not between μt and any of the determined properties of articular cartilage (P > 0.05).ConclusionMultivariate analysis of OCT signal provided good estimates for tissue structure, composition and mechanical properties. This technique may significantly enhance OCT evaluation of articular cartilage integrity, and could be applied, for example, in delineation of degenerated areas around cartilage injuries during arthroscopic repair surgery

Simultaneous ultrasound measurement of articular cartilage and subchondral bone

SummaryObjectiveIn osteoarthritis (OA), subchondral sclerosis takes place during cartilage degeneration. High frequency ultrasound (12–55MHz) has been shown to diagnose degenerated articular cartilage, while 0.1–1MHz ultrasound has been applied for clinical characterization of bone and diagnostics of osteoporosis. The aim of the study is to investigate, for the first time, the feasibility of 5MHz ultrasound for simultaneous analysis of articular cartilage and subchondral bone.MethodsOsteochondral samples (n=10) were prepared from fresh and visually normal bovine medial tibial plateaus. Acoustic properties of the cartilage and subchondral bone were measured with a scanning ultrasound system using the pulse-echo geometry and compared with biomechanical, histological and compositional reference data.ResultsThe apparent integrated backscatter (AIB) from internal cartilage showed significant partial correlations with hydroxyproline (Hypro) (r=0.58, P=0.000), water content (r=−0.52, P=0.001) and dynamic modulus (r=0.57, P=0.000) of the tissue. Weak but statistically significant correlation was found between the bone AIB and mineral density of the subchondral plate (r=−0.34, P=0.041). Topographical variations in cartilage thickness could be detected using ultrasound. Composition, thickness and mechanical properties of the cartilage varied significantly across the tibial plateau. For the calculated ultrasound parameters, the variation was significant only between a few locations.ConclusionsPulse-echo ultrasound geometry at 5MHz was feasible for simultaneous measurement of the acoustic properties of articular cartilage and subchondral bone. However, the relationships between the ultrasound parameters and properties of cartilage and bone were not as strong as reported earlier in studies focusing only either on bone or cartilage. Simultaneous measurement of both tissues compromises, due to natural curvature of articulating surfaces, the perpendicularity of the incidence of the ultrasound pulse. Obviously, this source of uncertainty should be minimized in order to enable effective clinical use of ultrasound in simultaneous measurement of articular cartilage and subchondral bone

Characterization of articular cartilage by combining microscopic analysis with a fibril-reinforced finite-element model

ABSTRACT: Load-bearing characteristics of articular cartilage are impaired during tissue degeneration. Quantitative microscopy enables in vitro investigation of cartilage structure but determination of tissue functional properties necessitates experimental mechanical testing. The fibril-reinforced poroviscoelastic (FRPVE) model has been used successfully for estimation of cartilage mechanical properties. The model includes realistic collagen network architecture, as shown by microscopic imaging techniques. The aim of the present study was to investigate the relationships between the proteoglycan and collagen content as assessed by quantitative microscopic findings, and model-based mechanical parameters of the tissue. Site-specific variation of the collagen network moduli, proteoglycan matrix modulus and permeability was analyzed. Cylindrical cartilage samples (n=22) were harvested from various sites of the bovine knee and shoulder joints. Collagen orientation, as quantitated by polarized light microscopy, was incorporated into the finite element model. Stepwise stress-relaxation experiments in unconfined compression were conducted for the samples, and sample-specific models were fitted to experimental data in order to determine values of the model parameters. For comparison, Fourier transform infrared imaging and digital densitometry were used for the determination of collagen and proteoglycan content in the same samples, respectively. The initial and strain-dependent fibril network moduli as well as the initial permeability correlated significantly with the tissue collagen content. The equilibrium Young¿s modulus of the non-fibrillar matrix and the strain-dependency of permeability correlated significantly with the tissue proteoglycan content. The present study demonstrates that modern quantitative microscopic methods in combination with the FRPVE model are feasible methods to characterize the structure-function relationships of articular cartilage