Integrative Repair and Collagen Crosslinking in Articular Cartilage

Articular cartilage is a connective tissue at the end of long bones that acts as a bearing surface during joint articulation. However the mechanical properties of cartilage can be altered as pathological conditions and abnormal loading can lead to cartilage lesions and/or overall degeneration of the tissue. The complete repair of an articular cartilage defect requires integration of opposing cartilage surfaces or the integration of repair tissue with the surrounding host cartilage. Unfortunately, integrative cartilage repair does not occur readily in vivo. Therefore, in vitro studies that attempt to determine and enhance the mechanisms that govern repair can be useful in formulating clinical therapies and interventions.

This dissertation begins with general reviews of articular cartilage metabolism, composition, and structure and the biomechanics of cartilage repair. The review of collagen metabolism, in particular, provides a framework for the biological basis for integrative repair. In addition, the biomechanics of integrative cartilage repair are addressed as both strength of materials and fracture mechanics approaches to mechanically assessing integrative repair are reviewed.

The scientific objectives of this dissertation are to determine the role of extracellular processing of newly synthesized collagen in integrative repair and the kinetics of collagen crosslinking in bovine cartilage explants. In an in vitro system, the effect of B-aminopropionitrile on collagen extractability and integrative cartilage repair, assessed using a strength of materials approach, were investigated. Results from these studies indicated that a specific alteration in extracellular collagen processing may be related to impaired repair in vitro. However, there was no information available on the kinetics of enzyme-mediated collagen crosslinking in articular cartilage. As a result, pulse-chase studies and a kinetic model were used to determine the rate of formation of newly synthesized reducible and mature crosslinks and characteristic time constants.

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Year

Entry

1989

Heinegård D, Oldberg Å. Structure and biology of cartilage and bone matrix noncollagenous macromolecules. FASEB J. July 1989;3(9):2042-2051.

1994

Ateshian GA, Lai WM, Zhu WB, Mow VC. An asymptotic solution for the contact of two biphasic cartilage layers. J Biomech. November 1994;27(11):1347-1360.

1984

Huberti HH, Hayes WC. Patellofemoral contact pressures: the influence of Q-angle and tendofemoral contact. J Bone Joint Surg. June 1984;66A(5):715-724.

1989

Sah RL-Y, Kim Y-J, Doong J-YH, Grodzinsky AJ, Plass AHK, Sandy JD. Biosynthetic response of cartilage explants to dynamic compression. J Orthop Res. 1989;7(5):619-636.

1979

Maroudas A. Physicochemical properties of articular cartilage. In: Freeman MAR, ed. Adult Articular Cartilage. 2nd ed. Kent, England: Pitman Medical; 1979:215-290.