Institute of Bone and Joint Research Symposium Regeneration and repair of connective tissues: Fact or fiction? 24 November 2001, University of Sydney, Australia
Authors: Handley C. 
Published: March 2003

Articular cartilage is an avascular, aneural and alymphatic tissue that covers the ends of bones and is responsible for the distribution of mechanical loads over the surface area of the subchondral bone as well as giving a near frictionless surface. Cartilage is made up of chondrocytes embedded in an extracellular matrix and it is the presence of aggrecan complexes trapped within the insoluble collagen network that gives articular cartilage its unique biomechanical properties. Articular cartilage obtains nutrients from the synovial fluid; joint movement and compression are important in facilitating the movement of nutrients into, and waste molecules out of, the extracellular matrix. During growth, chondrocytes are responsible for the expansion of the extracellular matrix that is part of endochrondral bone growth. In diseases such as osteoarthritis, chondrocytes have the capacity to degrade the extracellular matrix of cartilage that can result in the complete loss of cartilage from the surface of bones.Studies have revealed that articular cartilage is an extremely complex structure at the cellular and molecular level. Articular cartilage has been shown to be made up of a number of distinct layers that contain chondrocytes that have distinctive morphologies and metabolism. It has also been shown that chondrocytes from weight‐bearing and non‐weight‐bearing regions of articular cartilage have different metabolic characteristics, which suggest that chondrocytes are sensitive to their biomechanical environment. Studies have shown that the extracellular matrix is made up by the interaction of many individual molecular components and is a complex structure that shows heterogeneity in its organization. The collagen network is made up of type II/XI collagen fibres that are crossed‐linked by type IX collagen. Associated with the collagen network are small proteoglycans and noncollagenous proteins that appear to be involved in the stabilization and organization of the extracellular matrix through specific matrix–matrix and matrix–cell interactions. The extracellular matrix surrounding each chondrocyte can be divided into three distinct regions. The pericellular matrix that surrounds each chondrocyte is rich in aggrecan complexes and contains a paucity of collagen fibres; encapsulating the pericellular matrix is the territorial matrix defined by a basket arrangement of collagen fibres. Joining the territorial matrix surrounding each chondrocyte is the interterritorial matrix that makes up the bulk of the extracellular matrix of articular cartilage and contains aggrecan complexes. The collagen fibres in the interterritorial region are either arranged in large bundles that form arcade‐like structures that are continuous through all the layers of the tissue or they are arranged in a random manner in association with the large collagen bundles.Articular cartilage has the ability to replace aggrecan complexes that have been lost from the extracellular matrix, but it is evident that if the collagen network is damaged then cartilage is unable to achieve a long‐term repair of the damaged network. The ability of articular cartilage to repair is compromised by the lack of an inflammatory wound‐repair response and this is evidenced by the inability of partial‐thickness injuries of the tissue to repair. Full‐thickness injuries that result in bleeding from the bone surface show such an inflammatory wound‐repair response that gives rise to the formation of a clot that is then infiltrated by cells that synthesize an extracellular matrix. In this situation only partial repair of the injured area is usually achieved and in the long term the repaired matrix will degenerate. It has been suggested that the reason for this degeneration is that there is a lack of biomechanical integrity between the original and restored matrix. The degeneration of the repaired matrix occurs as a combination of the metabolic activity of the cells within the repair and by mechanical failure of the restored matrix. This work shows that cartilage has a potential to repair but in order to elicit a mechanically stable repair, consideration needs to be given to obtaining a mechanical continuum between the original and restored matrix. Indeed, the challenge appears to be in the present inability to manipulate the interactive processes that are involved in the formation of the extracellular matrix and reflects the complexity of the cellular and molecular organization of articular cartilage.