Human Tibial Cartilage Research Articles

High-resolution infrared microspectroscopic characterization of cartilage cell microenvironment

The lateral resolution of infrared spectroscopy has been inadequate for accurate biochemical characterization of the cell microenvironment, a region regulating biochemical and biomechanical signals to cells. In this study, we demonstrate the capacity of a high-resolution Fourier transform infrared microspectroscopy (HR-FTIR-MS) to characterize the collagen content of this region. Specifically, we focus on the collagen content in the cartilage cell (chondrocyte) microenvironment of healthy and osteoarthritic (OA) cartilage. Human tibial cartilage samples (N = 28) were harvested from 7 cadaveric donors and graded for OA severity (healthy, early OA, advanced OA). HR-FTIR-MS was used to analyze the collagen content of the chondrocyte microenvironment of five distinct zones across the tissue depth. HR-FTIR-MS successfully showed collagen content distribution across chondrocytes and their environment. In zones 2 and 3 (10 - 50% of the tissue thickness), we observed that collagen content was smaller (P < 0.05) in early OA compared to the healthy tissue in the vicinity of cells (pericellular region). The collagen content loss was extended to the extracellular matrix in advanced OA tissue. No significant differences in the collagen content of the chondrocyte microenvironment were observed between the groups in the most superficial (0–10%) and deep zones (50–100%). HR-FTIR-MS revealed collagen loss in the early OA cartilage pericellular region before detectable changes in the extracellular matrix in advanced OA. HR-FTIR-MS-based compositional assessment enables a better understanding of OA-related changes in tissues. This technique can be used to identify new disease mechanisms enabling better intervention strategies. Statement of significanceOsteoarthritis (OA) is the most common degenerative joint disease causing pain and disability. While significant progress has been made in OA research, OA pathogenesis is still poorly understood and current OA treatments are mainly palliative. This study demonstrates that high-resolution FTIR microspectroscopy (HR-FTIR-MS) can characterize OA-induced compositional changes in the cell microenvironment (pericellular matrix) during the early disease stages before tissue changes in the extracellular matrix become apparent. This technique may further enable the identification of new OA mechanisms and improve our current understanding of OA pathogenesis, thus, enabling the development of better treatment methods.

Structure\u2013Function Relationships of Healthy and Osteoarthritic Human Tibial Cartilage: Experimental and Numerical Investigation

Relationships between composition, structure and constituent-specific functional properties of human articular cartilage at different stages of osteoarthritis (OA) are poorly known. We established these relationships by comparison of elastic, viscoelastic and fibril-reinforced poroelastic mechanical properties with microscopic and spectroscopic analysis of structure and composition of healthy and osteoarthritic human tibial cartilage (n = 27). At a low frequency (0.005 Hz), proteoglycan content correlated negatively and collagen content correlated positively with the phase difference (i.e. tissue viscosity). At a high-frequency regime (> 0.05 Hz), proteoglycan content correlated negatively and collagen orientation angle correlated positively with the phase difference. Proteoglycans were lost in the early and advanced OA groups compared to the healthy group, while the superficial collagen orientation angle was greater only in the advanced OA group compared to the healthy group. Simultaneously, the initial fibril network modulus (fibril pretension) was smaller in the early and advanced OA groups compared to the healthy group. These findings suggest different mechanisms contribute to cartilage viscosity in low and high frequencies, and that the loss of superficial collagen pretension during early OA is due to lower tissue swelling (PG loss), while in advanced OA, both collagen disorganization and lower swelling modulate the collagen fibril pretension.

T1ρ-based fibril-reinforced poroviscoelastic constitutive relation of human articular cartilage using inverse finite element technology.

Mapping of T1ρ relaxation time is a quantitative magnetic resonance (MR) method and is frequently used for analyzing microstructural and compositional changes in cartilage tissues. However, there is still a lack of study investigating the link between T1ρ relaxation time and a feasible constitutive relation of cartilage which can be used to model complicated mechanical behaviors of cartilage accurately and properly. Three-dimensional finite element (FE) models of ten in vitro human tibial cartilage samples were reconstructed such that each element was assigned by material-level parameters, which were determined by a corresponding T1ρ value from MR maps. A T1ρ-based fibril-reinforced poroviscoelastic (FRPE) constitutive relation for human cartilage was developed through an inverse FE optimization technique between the experimental and simulated indentations. A two-parameter exponential relationship was obtained between the T1ρ and the volume fraction of the hydrated solid matrix in the T1ρ-based FRPE constitutive relation. Compared with the common FRPE constitutive relation (i.e., without T1ρ), the T1ρ-based FRPE constitutive relation indicated similar indentation depth results but revealed some different local changes of the stress distribution in cartilages. Our results suggested that the T1ρ-based FRPE constitutive relation may improve the detection of changes in the heterogeneous, anisotropic, and nonlinear mechanical properties of human cartilage tissues associated with joint pathologies such as osteoarthritis (OA). Incorporating T1ρ relaxation time will provide a more precise assessment of human cartilage based on the individual in vivo MR quantification.

Elastic, Viscoelastic and Fibril-Reinforced Poroelastic Material Properties of Healthy and Osteoarthritic Human Tibial Cartilage

Articular cartilage constituents (collagen, proteoglycans, fluid) are significantly altered during osteoarthritis (OA). A fibril-reinforced poroelastic (FRPE) material model can separate the contribution of each constituent on the mechanical response of cartilage. Yet, these properties and their OA related alterations are not known for human tibial cartilage. To answer this gap in the knowledge, we characterized the FRPE as well as elastic and viscoelastic properties of healthy and osteoarthritic human tibial cartilage. Tibial osteochondral explants (n = 27) harvested from 7 cadavers were mechanically tested in indentation followed by a quantification of elastic, viscoelastic and FRPE properties. Then they were histopathologically OARSI graded for the severity of OA. FRPE modeling revealed that non-fibrillar matrix modulus was higher in the healthy group compared to the early OA (p = 0.003) and advanced OA (p < 0.001) groups. The initial fibril network modulus was also higher in the healthy group compared to the early OA (p = 0.009) and advanced OA (p < 0.001) groups. The permeability correlated with the OARSI grade (p = 0.002, r = 0.56). For the first time, the FRPE properties were characterized for human tibial cartilage. This knowledge is crucial to improve the accuracy of computational knee joint models.

Evaluation of hyperelastic models for the non-linear and non-uniform high strain-rate mechanics of tibial cartilage

Accurate modeling of the high strain-rate response of healthy human knee cartilage is critical to investigating the mechanism(s) of knee osteoarthritis and other cartilage disorders. Osteoarthritis has been suggested to originate from regional shifts in joint loading during walking and other high strain-rate physical activities. Tibial plateau cartilage under compression rates analogous to walking exhibits a non-linear and location-dependent mechanical response. A constitutive model of cartilage that efficiently predicts the non-linear and non-uniform high strain-rate mechanics of tibial plateau cartilage is important for computational studies of osteoarthritis development. A transversely isotropic hyperelastic statistical chain model has been developed. The model's ability to simulate the 1-strain/s unconfined compression response of healthy human tibial plateau articular cartilage has been assessed, along with two other hyperelastic statistical chain models. The transversely isotropic model exhibited a superior fit to the non-linear stress–strain response of the cartilage. Furthermore, the model maintained its predictive capability after being reduced from four degrees of freedom to one. The remaining material constant of the model, which represented the local collagen density of the tissue, demonstrated a regional dependence in close agreement with physiological variations in collagen density and cartilage modulus in human knees. The transversely isotropic eight-chain network of freely jointed chains with a regionally-dependent material constant represents a novel and efficient approach for modeling the complex response of human tibial cartilage under high strain-rate compression. The anisotropy and microstructural variations of the cartilage matrix dictate the model's response, rendering it directly applicable to computational modeling of the human knee.

Dynamic Biomechanics Correlate with Histopathology in Human Tibial Cartilage

Improved staging of cartilage degeneration is required, particularly during early stages when minimal surface damage is visible arthroscopically. Degradation of articular cartilage extracellular matrix, resulting from degenerative changes associated with osteoarthritis, can influence its functional properties. Cartilage mechanical properties therefore may provide a quantitative method for monitoring degenerative change in this tissue. We determined whether dynamic mechanical properties of cartilage (effective shear modulus and phase lag) measured with a handheld indenter correlated with histopathology scores, proteoglycan, and collagen content or expression of chondrocyte-specific (aggrecan, collagen II) or dedifferentiation (collagen I and III) genes in human osteoarthritic cartilage with International Cartilage Repair Society scores of 0 to 1. We observed an association between the histopathologic stage of cartilage disease and dynamic shear modulus and phase lag. In contrast, there generally was a poor relationship between cartilage biomechanical properties and biochemistry with the only noteworthy correlation being between shear modulus and collagen. Phase lag but not shear modulus correlated with gene expression. These data support the potential of dynamic indentation for assessing the stage of cartilage degeneration in tissue with minimal gross surface damage.