Biomimetic Nanofi brous Scaffolds for Bone Tissue Engineering Applications - Biomimetics: Advancing Nanobiomaterials and Tissue Engineering - page 72

Recently techniques for producing nanofi brous surface features on the
order of 1-1000 nm in 3D constructs have been shown to induce simi-
lar cellular behavior to that seen on natural surfaces, without any special
material treatment or coating, such as RGD ligand attachment. Three pri-
mary methods of fabricating 3D scaffolds with a nanofi brous structure
exist: self-assembly, electrospinning, and thermally induced phase sepa-
ration (TIPS). The advantages and biological properties of each will be
addressed in turn.

4.2 Self-Assembled Nanofi ber Scaffolds

4.2.1 Fabrication and Physical Properties

Self-assembly is the process by which simple components spontaneously
form complex structures as a consequence of their intrinsic properties [36].
The concept originated from observation of biological molecules such as
phospholipids, which spontaneously form lipid membranes and spheres
[37], and of structural proteins such as collagen, which assemble into rope-
like fi brils [38]. Initial attempts at synthesizing self-assembling molecules
attempted to emulate the behavior of collagen proteins which self-assemble
into fi brils, or of phospholipids which create micelles or membranes [39,
40]. These molecules formed spheres or membranes in aqueous solutions
similar to biologically derived phospholipids whose structure they closely
emulate. More complex molecules incorporating a hydrophobic fatty
acid region, cysteine residues to induce disulfi de crosslinking between
monomers, and attachment of functional groups such as growth factor
fragments or calcium chelators to induce mineralization were soon devel-
oped [41]. These molecules are typically called peptide amphiphiles (PA),
to indicate they include both hydrophilic peptide and hydrophobic lipid
domains. PAs can be assembled into a variety of forms including micelles
and sheets, but their most common use in tissue engineering is to produce
a nanofi brous gel, with fi bers on the order of 1 m m in length and ~10 nm in
diameter [41, 42] (Figure 4.1). A unique advantage of PA gels is the ability
to self-assemble in physiological conditions, allowing for the encapsula-
tion of live cells into a gel, or for an injectable liquid to be inserted into the
wound site, which then gels in vivo . While other types of self-assembling
molecules exist [42], the vast majority of interest for TE applications has
been with peptide amphiphile scaffolds due to their demonstrated capabil-
ity to form a nanofi brous gel and their excellent biocompatibility.
The primary drawback of self-assembling systems is the inability to
control scaffold microstructure as well as poor mechanical properties. PAs
form gels with nanometer-sized pore spaces between individual nanofi -
bers, and no techniques for creating PA scaffolds with macropores more