Biomimetic Nanofi brous Scaffolds for Bone Tissue Engineering Applications - Biomimetics: Advancing Nanobiomaterials and Tissue Engineering - page 71

While natural materials offer excellent bioactivity, techniques for fab-
ricating them into a suitable scaffold structure have often proven elusive.
An alternate way is the biomimetic approach, i.e., utilizing a non-natural
material that exhibits similar cellular interactions as biological materials,
which may also overcome potential immune rejection and pathogen trans-
mission concerns associated with naturally-derived biomaterials from
cadaver or animal sources. Initial developments in this area focused on
attaching small peptide sequences to synthetic materials in an attempt to
provide more natural cell attachment sites [25, 26]. As an example, one
can attach integrin-binding peptide sequences such as the RGD bind-
ing motif to artifi cial polymers and metals, which result in increased cell
adhesion and osteogenic activity [27]. This approach separates the scaf-
fold morphology and chemical activity-allowing for each to be optimized
independently. For more detailed information on peptide functionaliza-
tion of surfaces, see a review of the subject by Hersel et al. [27]. By similar
reasoning, incorporating hydroxyapatite mineral coatings or particles on
non-natural materials appears to enhance osteoconduction in metals and
polymers that would not normally interact with bone tissue [28, 29]. These
methods are not without drawbacks—surface modifi cation with ligand
binding sites on complex surfaces could be impractical for large-scale fab-
rication and coatings will eventually degrade in vivo , leaving bare syn-
thetic surfaces.
More recent developments have tried to replicate not just the chemical
features of a biological surface, but the morphology as well. Many ECM
proteins self assemble into ropelike fi bers a few nanometers in diameter
and several microns in length. It was hypothesized that by mimicking this
structure, more natural cellular behavior could be achieved [30]. In general
terms, micron scale features control cellular shape and spreading direction,
and nanoscale roughness controls cellular adhesion and chemical interac-
tion with the surface [31-34]. These behaviors are intertwined—cell shape
affects differentiation, and surface adhesion affects cell migration speed,
among others, and untangling each cause and effect relationship has
proven diffi cult. Note that it is not just the scale of the features, but their
organization. An experiment using fi brinogen binding islands at various
spacings and alignments demonstrated that stem cell differentiation into
osteogenic or adipogenic phenotypes was controlled not just by the den-
sity or size of adhesion points, but also by their arrangement [35]. Much
work remains to be done in this area as each study utilizes differing mate-
rial surfaces, means of texturing, and cell types, making general guidelines
diffi cult to formulate. While studies of 2D patterned surfaces are useful for
determining basic relationships between surface topography and cellular
behavior, it is not practical to use them to pattern the surface of a 3D scaf-
fold, and until recently there were no suitable techniques for producing a
three-dimensional scaffold with micro- or nanoscale topography.