A Basic Science Understanding of Cartilage Repair and Its Clinical Application

Articular Cartilage

Normal articular cartilage contains specialised hyaline cartilage of diarthrodial joints and functions by facilitating the transmission of loads and supporting very low levels of friction between the articulating surfaces under physiological conditions. ^, Articular cartilage represents a smooth surface of approximately 1 to 4 mm in thickness that overlies the subchondral bone and contacts synovial fluid. ^, The articular cartilage itself is devoid of vasculature, nerves and lymphatics and contains chondrocytes, specialised cells that respond to various mechanical and chemical signals to maintain matrix integrity. Cartilage contains a solid component composed of extracellular matrix and proteins that supply the structural framework and a fluid component composed of water, solutes, metabolites, small proteins and a high concentration of cations (Ca ²⁺ , K ⁺ , Na ⁺ , CL ^– ). The solid and fluid components contribute to the lubrication, mechanical stiffness, and load distribution functions of the articular cartilage. ^, Loading of the joint leads pressurises the interstitial fluid, which plays a major role in supporting compressive loads and preventing deformation of the solid matrix component. Because of the high specialisation of the tissue, limited mitotic ability of the chondrocytes and lack of vascularity, articular cartilage lacks the intrinsic repair potential that other tissue types such as bone or skin maintain through adulthood.

Components of Articular Cartilage

The articular cartilage tissue component is composed of the superficial, middle transitional, deep and calcified zones ( Fig. 21.1 ). Each zone contains of a cellular and extracellular matrix component primarily composed of proteoglycans (5% to 10%), collagen (10% to 20%) and water (68% to 85%). Proteoglycans are macromolecules composed of a protein core and polysaccharide chains called glycosaminoglycans . Aggrecan is the primary proteoglycan in articular cartilage that contributes to its net negative charge and maintains the high osmotic pressure, which is responsible for its mechanical function via fluid pressurisation. The matrix is primarily composed of collagen types II (90%), VI (1% to 2%), IX (1% to 2%) and XI (2% to 3%), which contribute to the matrix tensile strength and stiffness. The unique matrix architecture and composition vary with depth of the articular cartilage, with the respective chondrocyte density and morphology predicating its function and mechanical properties. ^,

The zonal cartilage organisation can also be defined by regions based on their distance from the chondrocytes – the pericellular, territorial and interterritorial regions. ^{, ,} The region most closely surrounding the chondrocytes is the pericellular matrix, which is composed of noncollagenous proteins and characterised by its high proteoglycan content. The territorial region consists of thin collagen fibrils that surround the individual regions of pericellular matrix and chondrocytes or clusters of multiple chondrocytes and their pericellular matrix. ^, The third, interterritorial region is the primary region of the articular cartilage and contains larger collagen fibrils whose alignment varies with depth and zone of the cartilage. ^,

Zone Organisation

The zone variations ( Fig. 21.1B ) are defined by differences in composition, collagen alignment and cross-linking and chondrocyte size, shape, function and metabolic activity. ^, The superficial zone is defined as the outermost layer of the articular cartilage contacting the synovial cavity and fluid, composed of the outer 10% to 20% of the articular cartilage total thickness. ^, This layer consists of densely packed flattened chondrocytes and collagen fibres oriented parallel to the articular surface, which contributes to the tensile strength of the articular cartilage. ^{, , ,} The superficial cells are responsible for secreting proteoglycan 4 (PRG4), a glycoprotein that supports lubrication. ^, This zone is further characterised by high fibronectin, water and elastin content. ^, The middle transitional zone (approximately 40% to 60% of total articular cartilage thickness) contains thicker collagen fibres and chondrocytes with a spherical morphology randomly distributed throughout the matrix. ^{, , , ,} The middle zone is characterised by high aggrecan and collagen type II content, which contributes to its increased compressive modulus. ^, The collagen fibre orientation in the middle transitional zone presents an obliquely arranged alignment known as part of the arcades of Benninghoff. ^{, ,} The deep zone, approximately 30% to 40% of the total articular cartilage thickness above the tidemark of the calcified cartilage region, contains fibres arranged perpendicular towards the articular surface with rounded chondrocytes arranged in clusters or columns. ^{, , ,} This zone contains the lowest cell density and high proteoglycan content contributing to the high compressive modulus of this region. ^, The calcified cartilage zone is a thin layer with thickness of approximately 50 m to 250 μm, varying by individual, location and mechanical loading. This biocomposite dense mineralized tissue and extracellular matrix (collagen type II, glycosaminoglycan, collagen type X) is separated from the articular cartilage by a histologically defined tidemark and functions to attach the noncalcified articular cartilage to the subchondral bone. ^{, ,} This region contains a gradient of mineral content with an exponential increase of this mineral content from the adjacent articular cartilage to the subchondral bone, conveying the mechanical properties of this region. ^{, ,}

In addition to variations in collagen alignment, the fluid and solid components of articular cartilage vary between zones, imparting their particular mechanical properties ( Fig. 21.1C ). Water content is most at the surface at approximately 80% wet weight (ww) and decreases linearly towards the subchondral bone to approximately 40% to 60% ww. The collagen content is highest in the superficial layer 86% dry weight (dw) and decreases with depth to approximately 67% dw in deep zone. Proteoglycans, the main noncollagen protein, are also depth dependent, with the lowest content at the superficial zone approximately 15% dw and increased content in the middle approximately 25% dw and deep zones 20% dw. ^{, , ,} In contrast, the porosity of the cartilage, or interstitial fluid content, is highest in the superficial zone and lowest in the middle and deep zones. Compared with the superficial zone with its high collagen content and increased tensile strength, the middle and deep zone contain increased proteoglycan and water content, with greater compressive strength. ^,