Harnessing Cell–Biomaterial Interactions for Osteochondral Tissue Regeneration - Tissue Engineering: Cell-Surface Interactions for Tissue Culture - page 71

primarily involved in maintaining the cartilage tissue by providing a balance
between degradation and synthesis of ECM molecules.
3.2 Extracellular Matrix
The ECM makes up approximately 95% of the total cartilage volume and thus has a
significant influence on the physical properties of cartilage [ 11 ]. The ECM comprises
collagen, proteoglycans, and glycoproteins, with the dry weight of cartilage containing
60%, 25-35%, and 15-20% of these molecules, respectively [ 9 ]. There are multiple
types of collagen such as types II, VI, and IX-XI [ 12 , 13 ]. Type II collagen is the
predominant collagen in cartilage (90-95% of collagen dry weight) [ 14 ]. The other
collagens are fibrillar and tend to interweave throughout the ECM to create a
framework that imparts tensile strength to the cartilage tissue [ 9 ]. Proteoglycans
contain a protein core, which accounts for 5% of the molecule, with the rest being
composed of branched glycosaminoglycans (GAGs) stemming from the protein
core. [ 3 ]. GAGs are composed of long, nonrepeating disaccharides with negatively
charged carboxylate/sulfate groups, such as hyaluronic acid (HA), decorin,
biglycan, keratin sulfate, chondroitin sulfate (CS), dermatan sulfate, and heparin
sulfate [ 9 , 10 ]. Proteoglycans are found within the pericellular matrix and are
known to aid in chondrocyte attachment to other matrix components [ 15 ]. Large
proteoglycan monomers tend to aggregate, which results in the formation of
aggrecan containing keratan sulfate and CS. Aggrecans can interact noncovalently
with hyaluronan, which is stabilized by link proteins [ 16 , 17 ]. The negative charge
of GAGs and proteoglycans imparts the tissue with a high degree of hydrophilicity,
and repulsion of these molecules has been linked to the compressive properties of
cartilage [ 18 ]. Additionally, these aggregated molecules can prevent a large dis-
placement of the cartilage matrix when undergoing compression, which confers
cartilage with its resiliency and durability. Glycoproteins are simply polypeptides
that are covalently attached to a carbohydrate group, such as link protein, fibro-
nectin, laminin, vitronectin, thrombospondin, and tenascin-C, and are distributed
throughout the ECM [ 12 , 15 ]. Fibronectin contains specific amino acid sequences
that are responsible for cell binding such as Arg-Gly-Asp (RGD), Arg-Gly-Asp-
Ser, Leu-Asp-Val, and Arg-Glu-Asp-Val [ 19 ]. Glycoproteins also contain adhe-
sion sites for chondrocytes and multiple binding sites that are able to stabilize
collagens and proteoglycans in the tissue [ 15 ]. Superficial chondrocytes produce
lubricin, also known as proteoglycan 4 or superficial zone protein, which is another
glycoprotein that has been found within the synovial fluid to facilitate joint
lubrication [ 20 ].