Scaffold Design for Bone Tissue Engineering: From Micrometric to Nanometric Level - Biologically Responsive Biomaterials for Tissue Engineering - page 8

polymeric pore surface by Simulated Body Fluid (SBF) treatment [ 58 ] with an ions
concentration, at least, equal to that of the human blood plasma [ 1 ] . However, some
authors have proposed to accelerate the conventional biomimetic process from 7 to
28 days down to few days by using supersaturated SBF, thus confirming the inter-
dependence between ionic strength and pH, as well as the influence of the substrate
chemistry on the formation of the resultant apatite [ 4 ] .
Alternatively, some authors proposed to combine bulk sol-gel transition and
surface biomimetic techniques. The sol-gel reaction allows to finely disperse cal-
cium phosphate nanoparticles into a polycaprolactone (PCL) matrix with an
expected improving of the functional features (i.e., mechanical response) as reported
in previous works [ 35 ]. Meanwhile, the controlled deposition of HA crystals by
accelerating simulated body fluid (5× SBF) allows forming a biologically active
surface which can drastically improve the bonding to living bone [ 23 ] . Proposed
integrated approach enables to efficiently exploit the peculiar features of composite
material bulk and surfaces by modulating the spatial distribution of bioactive sig-
nals, moving towards a more efficient replacement of bone tissue.
Since the apatite particles are generated from aqueous solution, this technique
may be used for biomimetically coating porous scaffolds with highly complex
surfaces, unlike many other surface modification methods which are restricted to
flat surfaces or very thin porous layers. This technique involves the use of bio-
compatible solution at mild conditions (body temperature reaction), extending the
variety of polymers or composite materials to be potentially used. Moreover, apa-
tite crystals are more similar to natural bone mineral in terms of low crystallinity
and nanometric size of crystals, beneficially affecting degradation and remodeling
properties. In vitro experiments showed that mineral crystals grow on composite
materials just after 7 days in supersaturated biological solution (5× SBF) [ 47 ] .
It was not surprising that higher concentration facilitated apatite formation, since
it was reported [ 58 ] that increasing the ionic concentrations of an SBF above the
saturation limit is a practical way to facilitate apatite nucleation and growth.
Other recent studies have reported that the formation of apatite on artificial mate-
rials is induced by functional groups which could reveal negative charge and further
induce apatite via the formation of amorphous calcium phosphate (Fig. 1.3 ). After
7 days of soaking in 5× SBF, the composite material was uniformly covered with a
calcium phosphate crystals layer with a thickness of few microns. In particular, rose
petal-like apatite crystallites composed mainly of hydroxyapatite are detected with
a Ca/P molar ratio of 1.67, typical of natural hydroxyapatite. Moreover, in this case,
a large presence of HA crystals has been recognized along the inner pore walls of
the porous scaffolds, confirming that the high concentration of SBF solution is
capable to induce a faster and uniformly distributed deposition. In particular, the
copious formation of apatite-like globular crystals on the exposed surfaces of the
composite scaffolds will be directly correlated to the improvement offered by nano-
scaled HA particles on the mechanisms of osteointegration [ 47 ] .
However, long treatment times (7-14 days) often are not completely compat-
ible for tissue engineering scaffolds which are composed of highly degradable