br Cartilage Cartilage is a flexible avascular aneural and a
Cartilage Cartilage is a flexible, avascular, aneural and alymphatic connective tissue. Its constituent cells, called chondrocytes, receive nutrients through diffusion from the synovial fluid, which is rich in proteins derived from the blood plasma, and from the joint tissues (hyaluronic acid, PRG4) . Articular cartilage (AC) is a specialized form of hyaline cartilage with a thickness of 2–4 mm. The ECM of AC has the capacity to retain high quantities of water due to its abundance of sulfated glycosaminoglycans, that possess strong hydrophilicity and negative charges . This property is intrinsically connected with the main function that AC has, namely allowing movement without friction and counteracting the impact of Omadacycline forces applied onto the joint . Given that AC is a viscoelastic “composite” dominated by two phases (gel and solid), it can respond to mechanical stimuli in two different ways: i) by deforming the porous matrix, which implies an increase in the number of contact points and a decrease of contact stresses; ii) by releasing interstitial fluid through the porous matrix consequently raising the lubrication of AC . Concerning biomechanics, a deep comprehension of the ECM components of AC is required beforehand. Type II collagen in the form of cross-linked microfibrils has been shown to form over the ECM. These fibrils make connections with other tissue-specific collagens of the cartilage, such as types IX and XI collagen among others (type VI, X, XII and XIV). Although the latter collagen types are almost insignificant components of the ECM in proportion, it seems they have a crucial role in the biomechanical behavior of the whole structure . Other important molecules involved in the composition of the ECM are the proteoglycans, mainly aggrecan and, in lesser amounts, biglycan, decorin and others (e.g. fibromodulin, lumican) . These uncommon proteoglycans are involved in the arrangement of the AC natural structure thanks to several interactions with collagen II alongside with Transforming Growth Factor (TGFβ) and keeping the fixed charge density constant which regulates water concentration . Aggrecan is involved in the two principal functions of the cartilage from a biomechanical point of view: i) Together with other molecules (i.e. chondroitin sulfate), it modulates the fluid pressurization of the tissue thus the structure can be maintained and the articular surface resists deformations allowing a major lubrication; ii) the concentration of aggrecan increases through the superficial zone and this gradient is correlated with the amount of extracellular water retention that inhibits external compressions .
Osteoarthritis: a biomechanical disease OA (Fig. 1A) is by far, the most representative degenerative disease related with the joints. It has been estimated that 250 million people worldwide suffer from of knee OA (2012), being a major cause of pain and disability in adults . The Global Burden of Disease (GBD) estimated that OA approximates 0.6% of all disability-adjusted life-years (DALYs) and 10% in musculoskeletal conditions . The pathological pathway leading to OA consists on a chronic low-grade degradation of AC (Fig. 2), which is the major driver of ongoing joint degeneration . In such a way, OA should not be considered as a disease but as a common end of multiple secondary pathways related with aging, possible traumas, obesity and their correspondence altered biomechanics of the joint . More and more researchers have supported this idea, which in principle could seem ambitious, during the last years. Ganz et al. in 2008 first introduced the suggestion that the early steps of OA process are related to biomechanical aspects of the cartilage tissue (Fig. 1B) , and recently, other authors have experimentally confirmed this statement . Inside the biomedical research community, it is globally accepted that biomechanical properties of the tissue behave as function of the ultrastructural organization which depends on the biochemistry and cell-cell and ECM-cell interactions  to such an extent that any small alteration in these properties will drastically alter tissue biomechanics . The main axis of the development of OA is a precedent of mechanical derangement that produces a low-grade damage in the AC . Thus, from the biomechanical point of view, three different stages can be established in OA development: i) the proteolytic breakdown of the ECM, ii) the fibrillation and erosion of the cartilage surface and, iii) the beginning of synovial inflammation (Fig. 2) .