Future - Chitosan Based Hydrogels: Functions and Applications - page 465

and tissue is regarded as a composite material that is composed of cells and their extracel-
lular matrices (ECMs).
10.1.2 Cells and Their eCMs
The ECM is the extracellular part of animal tissue that usually provides structural support
to the animal cells in addition to performing various other important functions. The ECM,
cells, and capillaries are physically integrated in functional tissues. ECM is not only a
physical support for cells, but also provides a natural environment for cell proliferation
and differentiation or morphogenesis, which contributes to cell-based tissue regeneration
and organogenesis.
Components of the ECM are produced intracellularly by resident cells, and secreted into
the ECM via exocytosis. Once secreted, they then aggregate with the existing matrix. ECM
is composed of (1) fibers (collagen and elastin) and (2) a largely amorphous interfibrillary
matrix (mainly proteoglycans, noncollagenous cell-binding adhesive glycoproteins,
solutes, and water).
Collagen comprises a family of closely related but genetically, biochemically, and func-
tionally distinct molecules, which are responsible for tissue tensile strength. The most
common protein in the animal world, collagen provides the extracellular framework for all
multicellular organisms. The collagens are composed of a triple helix of three polypeptide
α-chains; about 30 different α-chains form at nearly 20 distinct collagen types. Types I, II,
and III are the interstitial or fibrillar collagens and are the most abundant. Types IV, V, and
VI are nonfibrillar (or amorphous) and are present in interstitial tissue and basement
membranes.
Glycosaminoglycans (GAGs) are highly charged (usually sulfated) polysaccharide chains
up to 200 sugars long, composed of repeating unbranched disaccharide units. GAGs are
divided into four major groups on the basis of their sugar residues: (1) hyaluronic acid: a
component of loose connective tissue and of joint fluid, where it acts as a lubricant; (2)
chondroitin sulfate and dermatan sulfate; (3) heparan sulfate and heparin; and (4) keratin
sulfate.
Elastins, in contrast to collagens, give elasticity to tissues, allowing them to stretch when
needed and then return to their original state. This is useful in blood vessels, lungs, skin,
and ligamentum nuchae, and these tissues contain high amounts of elastins. Elastins are
synthesized by fibroblasts and smooth muscle cells. Elastins are highly insoluble, and
tropoelastins are secreted inside a chaperone molecule, which releases the precursor mol-
ecule upon contact with a fiber of mature elastin. Tropoelastins are then deaminated to
become incorporated into the elastin strand. Diseases such as cutis laxa and Williams syn-
drome are associated with deficient or absent elastin fibers in the ECM.
Fibronectins are proteins that connect cells with collagen fibers in the ECM, allowing
cells to move through the ECM. Fibronectins bind collagen and cell surface integrins, caus-
ing a reorganization of the cell's cytoskeleton and facilitating cell movement. Fibronectins
are secreted by cells in an unfolded, inactive form. Binding to integrins unfolds fibronec-
tin molecules, allowing them to form dimers so that they can function properly. Fibronectins
also help at the site of tissue injury by binding to platelets during blood clotting and facili-
tating cell movement to the affected area during wound healing.
Laminins are proteins found in the basal laminae of virtually all animals. Rather than
forming collagen-like fibers, laminins form networks of web-like structures that resist ten-
sile forces in the basal lamina. They also assist in cell adhesion. Laminins bind other ECM
components such as collagens, nidogens, and entactins.