Development and Application of Naturally Renewable Scaffold Materials for Bone Tissue Engineering - The Nanoscience and Technology of Renewable Biomaterials - page 295

11.2 Natural Renewable Materials for Bone Tissue Engineering (BTE)

The primary role of the extracellular matrix (ECM) is to endow tissues with their spe-
cific mechanical and physicochemical properties while providing a platform for cell
attachment and migration. The ECM exerts a regulatory role in promoting or maintain-
ing cellular differentiation and phenotype expressions through its composition, structure,
and morphology. For bone tissue engineering, three groups of naturally renewable mate-
rials are commonly used: polysaccharides, fibrous proteins, inorganic materials, and any
combination thereof. Polysaccharides are composed of repeating sugar rings linked by
oxygen bonds, and in their natural state they function as membranes, participate in
cellular communication, and can act as sequestering agents. On the molecular level,
the tailoring of polysaccharides and their function can be controlled by their molecular
weight, stereochemistry, primary sequence, and chemical reactivity. Polysaccharides can
be derived from a number of resources with the most common forms including cellulose,
hyaluronan, chitosan, dextran, alginates, and starches, to name a few. The main differ-
ence between these materials is the location of the linking glucosidic bonds between
rings, the relative position of this linkage either being equatorial ( β )oraxial( α ), and
the presence of different pendant groups on each ring. Polysaccharides can be classified
into four broad categories and include the ribbon, hollow helix, crumpled, and loosely
jointed families (21).
Fibrous proteins are materials that are formed by repeating amino acid sequences and
possess four levels of organization. These materials are the major structural compo-
nents of tissues by providing high mechanical strength and resiliency. The mechanical
integrity of proteins is preserved by the various levels of organization of its molecular
and macroscopic arrangement which include its: (1) primary structure or the sequence
of amino acids, (2) secondary structure or conformation of the chain, (3) tertiary struc-
ture or polypeptide chain arrangement, and (4) quaternary structure or configuration
of multiple polypeptide chains. Fibrous proteins display one of the following confor-
mations or secondary structures: α -helix, β -sheet, triple helix, and random coil. The
most popular fibrous proteins used as scaffolding materials include collagen, silk, ker-
atin, and fibrin. Collagen is usually derived from mammalian sources, primarily from
bovine and human origin, and its functional unit is arranged in a triple helix where
three collagen molecules are intertwined. These molecules are known as tropocolla-
gen and are approximately 300 nm in length and 1.5 nm in diameter (19, 22). Type
I collagen is largely used in bone tissue engineering due to its natural occurrence and
large quantity in bone; thus numerous collagen based systems have been developed as
a starting point for bone tissue scaffolds. Silk is another fibrous protein that is pro-
duced by spiders and silkworms. This protein is composed of β -sheet structures that
allow the tight packing of stacked sheets of hydrogen bonded anti-parallel chains and
account for its high tensile modulus and elasticity (23, 24). Keratin is another protein
that displays either an α -helix or β -sheet structure (depending on source) along with
cysteine residues to create disulfide bridges for enhanced stability and strength (25).
Fibrin is the polymerized form of fibrinogen after it has been crosslinked with thrombin,
and is known for both its coagulation effects in blood and as an extracellular matrix
substitute (26).