## 2 Anatomy of Articular Cartilage
### Collagens  
The most structural macromolecule in the ECM is collagen, accounting for 60-85% of cartilage's dry weight [2,4]. The orientation of collagen fibrils varies depending on the zone of the articular cartilage [91]. Collagen types I, II, IV, V, VI, IX and XI are found in the ECM, but type II accounts for 90-95% of the total collagen, with the remaining types constituting a minor part, participating in the formation of fibrils and fibres associated with proteoglycan aggregates [2,4,43,92]. Intramolecular and intermolecular connections between fibrils influence the elasticity of the collagen network. In addition, proteoglycans that are mechanically coupled and bound to water form cross-links, which results in resistance to compressive forces, thereby increasing the tension in the collagen network. Tensile strength is the most important property of collagen fibres. In turn, compressive strength, elasticity and durability are provided by water-proteoglycan compounds. Collagen II represents the majority of the collagen found in hyaline cartilage [93]. It is the main indicator of differentiation of hyaline cartilage, as the predominant collagen of heterofibrils. Collagen II accounts for approximately 75% of foetal collagen, while its value increases to 90% as the tissue matures [94]. Collagen IX binds to other collagen IX molecules via covalent bonds and also binds to collagen II molecules via cross-linking bonds [95]. This type of collagen is only found in AC and a few other tissues, so it can be used as a marker to differentiate cartilage. With maturation, the expression of collagen IX is increased, which may indicate that it plays an important role in development [96]. In vivo studies have confirmed that collagen IX has an impact on the development and integrity of AC, prevents dysplasia of the bone epiphysis, and influences the development of the cartilage growth plate [97,98]. Collagen XI is a fibrillar collagen that combines with collagen II. It accounts for about 10% of the total collagen in foetal cartilage, while in adult tissue it is only 3% [94]. Collagen XI molecules bind to other collagen XI molecules via cross-links within heterofibrils [95]. This type of collagen has also been shown to reduce fibrinogenesis by inhibiting the growth of collagen II fibrils [99]. Collagen VI is found in the pericellular matrix immediately surrounding the chondrocytes [100]. It contains an Arg-Gly-Asp sequence by which it binds to chondrocyte receptors [101]. The interaction between collagen IV and chondrocytes contributes to mechanotransduction, which implies that replication of this collagen structure is important in order to create a suitable microenvironment for chondrocytes [102]. The collagen VI content constitutes less than 1% of the total collagen in an adult human [94]. Collagen I is produced in various connective tissues, but it is not usually expressed in the articular cartilage of the hyaline joint. Nevertheless, it is found in tissues such as the tendon, ligament, meniscus and disc of the temporomandibular joint. Collagen I is also observed in fibrocattilage, which fills defects in damaged AC [101]. In tissue-engineered AC, the expression of collagen I is undesirable. In vitro culture of chondrocytes can affect dedifferentiation and collagen production [103]. This allows collagen I to act as a marker of the differentiation state of chondrocytes in tissue engineering procedures [101]. Collagen X is found exclusively near bone. Immunohistochemistryistological studies have shown the presence of collagen X in the hypertrophic and calcifying cartilage zone [104]. Also, this type of collagen is expressed on the articular surface of maturing cartilage through certain cells, as well as in AC with osteoarthritisritis [105, 106, 107]. However, the presence of collagen X in tissue-engineered structures may indicate chondrocyte hypertrophy. A summary of the types and molecular structure of collagen in articular cartilage is shown in Table 1, based on [108].