Integrated Biomaterials Science

Tissue Engineering 889
unknown until recently, when a sufficient amount of data on ECM composition,
cell-binding molecules, transmembrane receptors, signal transduction
mechanisms, growth factors, hormones, and ion channel structures were
available. If the goal of tissue engineering is, in an ultimate analysis, the
imitation of natural tissues, all this mass of information will help researchers
in developing materials, templates, and scaffolds for in vitro reconstruction
of tissues.
31.2.1. ECM Composition
The extracellular matrix is composed of a great variety of molecules
and includes collagen family, elastic fibers, glycosaminoglycans and proteoglycans,
and adhesive glycoproteins. The different combination, immobilization,
and spatial organization of these secreted substances give rise to
different types of scaffolds that characterize the different body tissues and
organs.
Collagens. Collagen is the most abundant protein in the vertebrate
body which constitutes a heterogeneous class of proteins that shares some
similarities, such as triple helical domains and some characteristic amino
acid repeat units along the molecular backbone in which glycine is present
at every third amino acid (Gly-Xaa-Yaa). Up to now about 20 different
collagens have been characterized which exhibit different mechanical and
functional properties. Some collagens are specific for a given tissue, such as
type II collagen, which is found only in cartilage. Types I, II, and III are the
most abundant collagens of the human body that form fibrils responsible for
the tensile strength of the tissue. Other collagens, such as types IV, VII, IX,
X, and XII are found associated with collagen fibrils or organized in
networks as in basal laminae. In addition to mechanical and structural
functions, collagens play an important role in determining cell attachment
and spreading. In consequence of these properties, collagens influence cell
differentiation and movement. With regard to the role collagen can play in
tissue engineering techniques, it must be said that in various cell culture
systems the coating of the plastic surface of culture plates with collagen or
collagen-derived products (gelatin) is essential to promote cell adhesion and
proliferation, such as in the case of endothelial cell and hepatocyte cultures.
Cell adhesion is specifically mediated by the presence of cell surface
receptors that bind either directly to collagen or via interactive glycoproteins
(fibronectin, laminin, etc). Moreover, cross-linking of collagens with
chemical agents such as formaldehyde or glutaraldehyde allows the formation
of thermoset materials that can be molded in various shapes to obtain
seminatural scaffolds useful for tissue engineering and cell culture.
Glycosaminoglycans and Proteoglycans. Glycosaminoglycans (GAG)
are linear polysaccharides formed by repeating disaccharide units that may