Scaffold Design for Bone Tissue Engineering: From Micrometric to Nanometric Level - Biologically Responsive Biomaterials for Tissue Engineering - page 4

1.3 Designing Microstructure

To mimic the topological and microstructural characteristics of the ECM, a scaffold
has to present high degree of porosity, high surface-to-volume ratio, fully pore inter-
connection, appropriate pore size, and geometry control [ 14 ] . Although several
aspects still require further investigations, a large number of studies have just
explored the role of the scaffold topographical features in cellular response. These
studies demonstrated that the micro-architecture of the porous scaffold may guide
cell functions by regulating the interaction between cells, and the diffusion of nutri-
ents and metabolic wastes throughout the three-dimensional (3-D) construct, pro-
viding sufficient space for development and later remodeling of the organized tissue
[ 27, 43 ]. Moreover, morphological features (i.e., pore size) may support, in turn,
cell adhesion, molecular transport, vascularization, and osteogenesis. For instance,
small pores (with diameters of few microns) favor hypoxic conditions and induce
osteochondral formation before osteogenesis occurs [ 12, 29 ] . In contrast, scaffold
architectures with larger pores (several hundred microns in size) rapidly induce a
well-vascularized network and lead to direct osteogenesis [ 58 ] .
In this context, several technologies are progressively emerging to imprint a con-
trolled pattern of pores within polymeric matrices for triggering the bone formation.

1.3.1 Hierarchically Organized Architecture

Scaffolds for bone regeneration have to provide a highly interconnected porous
structure to guide cell ingrowth for tissue formation, while maintaining a sufficient
mechanical strength to supply the structural requirement of the substituted tissue.
However, the complex composition and structural organization of hard mineralized
tissues, such as bone, cannot be replicated using only a single material component
which often shows properties spanning in a limited range. In this context, the devel-
opment of composite scaffolds by combining two or more types of materials with
selected properties may represent an appropriate and advantageous solution, satis-
fying all the mechanical and physiological demands of the host tissue. To date,
polymer matrices reinforced by ceramic fillers such as hydroxyapatite and trical-
cium phosphates represent a promising material, able to mimic the collagen/
hydroxyapatite micro/macro-morphology of “native bone material” [ 16, 19 ] .
However, the varying success of these approaches may be attributed to a nonho-
mogeneous spatial distribution of the ceramic particles into the polymer matrix with
poor mechanical response and bioactivity. An alternative biomimetic approach is
founded on the use of polymer-based composite scaffold with controlled pore spa-
tial distribution and programmed degradation kinetics obtained by integrating
polymer continuous fibers. Indeed, continuous fibers integrated within the poly-
meric matrix are able to mimic the collagen fibers' spatial disposition of the ECM,
to guide the preferential cell growth, and to support the stress transfer from the
polymer matrix improving the mechanical properties of the scaffold.