Relationships between Structure, Composition and Function of Articular Cartilage

Articular cartilage is a highly specialized tissue at the ends of articulating bones. It provides a smooth and frictionless contact surface for joint movements. As cartilage degenerates in osteoarthrosis, joint motion causes pain and joint mobility decreases. During cartilage degeneration, the tissue exhibits changes in its mechanical properties even before the appearance of any visual symptoms. Since cartilage is composed of several components, i.e. collagen, proteoglycans (PGs) and interstitial water, the effect of these components on the mechanical response of cartilage and their role in the progression of osteoarthrosis needs to be carefully addressed. In this thesis work, quantitative microscopy, magnetic resonance imaging (MRI) and finite element analysis were used to study the relation between tissue constituents and the mechanical behavior of cartilage. Specifically, the role of collagen architecture on cartilage mechanics was investigated. Furthermore, the mechanical behavior of articular cartilage was simulated using microscopically determined composition and structure of the tissue. Collagen and PG contents of the tissue were found to be inter-related with the fibrillar (collagen specific) and non-fibrillar (PG specific) matrix moduli, respectively. Tissue permeability was associated with both collagen and PGs. The properties of the non-fibrillar cartilage matrix and intrinsic permeability were also found to correlate with the MRI longitudinal relaxation time, T1. Although the transverse relaxation time, T2, is known to reflect cartilage collagen architecture, determination of the collagen specific mechanical properties using MRI proved difficult. This was due to complexities in collagen architecture which were not reflected by the bulk T2. By accounting for the inhomogeneous collagen architecture in the model, the traditional indentation analysis of tissue modulus was improved. Finally, by applying the composition-based modeling theory, the mechanical behavior of human patellar cartilage under unconfined compression was predicted successfully using microscopically determined tissue composition and structure. In conclusion, quantitative imaging techniques may provide tools for the assessment of cartilage mechanical integrity. However, due to the complex collagen architecture and its effect on the mechanical response of cartilage, the collagen-specific mechanical properties cannot be easily assessed with the current MRI techniques. The composition-based modeling, combined with the quantitative microscopy techniques of tissue composition and structure, may enable prediction of cartilage mechanical behavior without mechanical testing. In the future, the challenges of imaging collagen architecture with MRI need to be overcome to enable clinical functional imaging of articular cartilage. National Library of Medicine Classification: QT 36, WE 103, WE 300, QU 55.3, QU 55.5 Medical Subject Headings: Cartilage, Articular; Biomechanics; Finite Element Analysis; Collagen; Proteoglycans; Permeability; Osteoarthritis; Materials Testing; Microscopy; Magnetic Resonance Imaging