Scaffold Design for Bone Tissue Engineering: From Micrometric to Nanometric Level - Biologically Responsive Biomaterials for Tissue Engineering - page 10

also form a bone-like apatite layer on their surface in the presence of highly
supersaturated solutions with ion concentration from one- to fivefold SBF salt
concentration [ 4 ]. Furthermore, several studies have demonstrated that an effec-
tive apatite growth can occur in the presence of specific environmental condi-
tions which influence the chemical solubility as well as the material surface
activation [ 40 ] .
In this case, a novel treatment combining the preliminary use of bioglasses
with supersaturated SBF solutions at different salt concentrations has been opti-
mized to overcome the applicability limitations of traditional treatments on highly
degradable polymers like HYAFF11 ® . The analysis performed on this biomimetic
HA-based scaffold evidenced that the proposed treatment supports the mineral-
ization occurring already at day 21 and significantly increased at day 35 [ 39 ] .
Apatite crystals on HYAFF11 ® scaffold seem to act as nucleation sites for the
deposition of inorganic bone components as we proved by light and electron
microscopy. In fact, on non-biomimetic HYAFF11 ® scaffold an immature miner-
alization started to occur only at day 35, where we have also found a lower
Collagen type I expression and increased cell proliferation, indicating that the
biomimetic treatment reduced the time taken to induce the process. Contrariwise,
biomimetic HYAFF11 ® scaffold promotes the precipitation of apatite crystals,
inducing the formation of new bone with a copious mineralization already at day
21 increasing up to day 35. These data suggest possible in vitro trophic effects of
h-MSCs [ 7, 10 ] in inducing mineralization processes that can be also influenced
by the composition [ 22 ] or elasticity [ 48 ] of the scaffold. In fact, HA not only
enhances hydroxyapatite crystal proliferation and growth, but it can also promote
mineralization [ 5 ] since it is a prominent extracellular matrix component during
the early stage of osteogenesis [ 53 ] .

1.5 Designing Nanostructures

In biological and medical applications, the capability of controlling physical and
chemical interactions at the level of natural building blocks, from proteins to cells,
may favor a more efficient exploration, manipulation, and application of living
systems and biological phenomena. In this context, nano-structured biomaterials in
the form of nanoparticles, nanofibers, nanosurfaces, and nanocomposites have
gained increasing interest in regenerative medicine because they often mimic the
physical features of natural ECM at the nanoscale level.
Besides, nanotechnology is emerging as an important tool in scaffold design to
reproduce the features of microenvironment-mediated signaling which determine
tissue specificity and architecture of native tissues. Currently, an important class
of nano-structured biomaterials on which intensive research has been carried out
is composed of nanofibrous materials, especially biodegradable polymer
nanofibers, able to morphologically mimic the fibrillar structure of ECM. In this
regard, the electrospinning represents a powerful strategy to develop biomimetic