New Concept to Restore Normal Cell Responses in Osteoarthritic Knee Joint Cartilage.

Prediction of osteoarthritis progression does not exist. Cartilage "health" and degeneration during osteoarthritis depend on the signals perceived by chondrocytes. We hypothesize that biomechanical responses of chondrocytes in osteoarthritic cartilage can be restored close to their normal state. We propose an approach to evaluate quantitatively these responses in human joints and demonstrate how they can return close to normal levels.

Topographical investigation of changes in depth-wise proteoglycan distribution in rabbit femoral articular cartilage at 4 weeks after transection of the anterior cruciate ligament.

In this study, we explore topographical changes in proteoglycan distribution from femoral condylar cartilage in early osteoarthritis, acquired from both the lateral and medial condyles of anterior cruciate ligament transected (ACLT) and contralateral (CNTRL) rabbit knee joints, at 4 weeks post operation. Four sites across the cartilage surface in a parasagittal plane were defined across tissue sections taken from femoral condyles, and proteoglycan (PG) content was quantified using digital densitometry. The greatest depth-wise change in PG content due to an ACLT (compared to the CNTRL group) was observed anteriorly (site C) from the most weight-bearing location within the lateral compartment. In the medial compartment, the greatest change was observed in the most weight-bearing location (site B). The depth-wise changes in PG content were observed up to 48% and 28% depth from the tissue surface at these aforementioned sites, respectively (p < 0.05). The smallest depth-wise change in PG content was observed posteriorly (site A) from the most weight-bearing location within both femoral condyles (up to 20% and up to 5% depth from the tissue surface at lateral and medial compartments, respectively). This study gives further insight into how early cartilage deterioration progresses across the parasagittal plane of the femoral condyle.

How the structural integrity of the matrix can influence the microstructural response of articular cartilage to compression.

This study investigated how the structural integrity of healthy, surface-removed (healthy), and degenerate matrices can modify the response of cartilage to compression. Six groups of specimens were loaded up to the onset of consolidation or at full consolidation (N = 30, 5 per group, respectively) and then subsequently chemically fixed to capture the deformed state of the tissues. Creep compression was applied through an 8 mm flat-ended indenter containing a 450 µm diameter central pore, providing a region of high stress that also allowed the tissue samples to deform freely around the indenter pore during compression. Differential interference contrast microscopy was used in order to explore the microstructural responses of the tissues. The results demonstrated that superficial layer removal or tissue degeneration can reduce the observed deformation within the tissue region corresponding to the central pore of the loading indenter. Fibril crimping within the central pore matrix and matrix shear at the indenter edge regions are also reduced by both superficial layer removal and by tissue degeneration. These findings suggest that surface removal or tissue degeneration renders the matrix more susceptible to deformation and can also reduce the tissue's ability to transfer forces over a greater surface area and induce stress within the matrix.

Articular cartilage surface failure: an investigation of the rupture rate and morphology in relation to tissue health and hydration.

This study investigates the rupture rate and morphology of articular cartilage by altering the bathing environments of healthy and degenerate bovine cartilage. Soaking tissues in either distilled water or 1.5 M NaCI saline was performed in order to render the tissues into a swollen or dehydrated state, respectively. Creep compression was applied using an 8 mm flat-ended polished indenter that contained a central pore of 450 microm in diameter, providing a consistent region for rupture to occur across all 105 tested specimens. Rupture rates were determined by varying the nominal compressive stress and the loading time. Similar rupture rates were observed with the swollen healthy and degenerate specimens, loaded with either 6 or 7MPa of nominal compressive stress over 11 and 13 min. The observed rupture rates for the dehydrated specimens loaded with 7 MPa over 60 and 90s were 20% versus 40% and 20% versus 60% for healthy and degenerate tissues, respectively. At 8 MPa of nominal compressive stress over 60 and 90s the observed rupture rates were 20% versus 60% and 40% versus 80% for healthy and degenerate tissues, respectively; with all dehydrated degenerate tissues exhibiting a greater tendency to rupture (Barnard's exact test, p < 0.05). Rupture morphologies were only different in the swollen degenerate tissues (p < 0.05). The mechanisms by which dehydration and swelling induce initial surface rupture of mildly degenerate articular cartilage differ. Dehydration increases the likelihood that the surface will rupture, however, swelling alters the observed rupture morphology.

Articular cartilage surface rupture during compression: investigating the effects of tissue hydration in relation to matrix health.

This study aimed at investigating articular cartilage rupture by investigating the response of healthy and degenerate cartilage through altering the osmotic swelling environment of surface-intact, cartilage-on-bone specimens. The osmotic environment in healthy and degenerate bovine cartilage was varied by soaking tissues in either distilled water or 1.5 M NaCl saline to render the tissues into a swollen or dehydrated state (respectively). Creep compression was applied using an 8 mm flat-ended polished indenter that contained a central pore of 450 µm diameter, providing a consistent region for rupture to occur across all specimens. In the first set of experiments, surface rupture of healthy and degenerate specimens required similar levels of nominal compressive stress (8 MPa) when dehydrated than when swollen (7 MPa). In the second set of experiments, the time required for surface rupture to occur (for healthy and degenerate specimens) occurred over similar loading times (p>0.05). However, the time required for surface rupture for the swollen specimens occurred over a significantly longer time (approximately one order of magnitude) than that required for the dehydrated specimens (p<0.05). The compressive strains that were measured at rupture in the dehydrated degenerate specimens were significantly lower than those measured in the dehydrated healthy tissues (p<0.05). Rupture in dehydrated degenerate cartilage suggested a weakened articular surface, and it also suggested that dehydrated cartilage may undergo failure due to stress concentrations as it is unable to redistribute stress away from the site of loading.

Articular cartilage compression: how microstructural response influences pore pressure in relation to matrix health.

Our research investigated the influence of degeneration on both the pore-pressure development and microstructural response of cartilage during indentation with a flat-porous-indenter. Experiments were conducted to link the mechanical and structural responses of normal and degenerate articular cartilage. We found that from the instant of loading the degenerate matrix generated a higher peak hydrostatic excess pore pressure in a shorter period of time than the normal matrix. Following the attainment of this peak value the pore pressure in both tissue groups then gradually decayed toward zero over time, thus demonstrating a classical consolidation response. The microstructural analysis provided a unique insight into the influence of degeneration on the mechanisms of internal stress-sharing within the loaded matrix. Both disruption of the articular surface and general matrix destructuring results in an altered deformation field in both the directly loaded and nondirectly loaded regions. It is argued that the higher levels of matrix shear combined with less of the applied load being redirected into the wider cartilage continuum accounts for the elevated levels of peak hydrostatic pore pressure generated in the degenerate matrix.