Optimization Approaches for the Design of Additively Manufactured Scaffolds - Tissue Engineering: Computer Modeling, Biofabrication and Cell Behavior - page 112

architectures. Most of these studies rely on the use of unit cells with well-known
geometric, mechanical, and fluid-flow properties, which can be assembled together
according to the application needs. Boolean operations between the 3D reconstruc-
tion of the defect site and the arranged stack of cellular units are required for the
construction of the final design. Hence, different libraries of unit cells have been
created, and algorithms have been developed to allow their automatic design and as-
sembly [ 10 ]. CAD-based libraries have been developed starting from regular poly-
hedral shapes [ 11 , 12 ] or using Boolean intersections between a solid domain and
geometric primitives, such as spheres and cylinders, to create the void spaces of
the porous element [ 12 ]. More recently, the use of unit cells based on CAD rep-
resentation of triply periodic minimal surfaces (e.g. gyroid and diamond) has been
proposed [ 13 , 14 ]. When replicated and assembled at the macro scale, these mor-
phologies showed a positive influence on cell migration and tissue in-growth while
representing an optimal biomorphic tissue architecture [ 15 ]. Furthermore, an image-
based approach has been introduced by Hollister et al. to design scaffold unit cells
simply setting voxels within a representative design element to 0 or 1, depending
on the presence or the absence of the material in the corresponding region. Several
strategies have been adopted for the creation of a variety of topologies with both reg-
ular and randomly distributed pores within the unit cell [ 16 ]. Image-based designs,
fitting diagnostic imaging data, have been generated and successively coupled with
optimization algorithms to match existing host tissue mechanical properties [ 17 ].
Another particular cellular solid has been obtained by stacking alternate layers of
filaments, such as those fabricated via extrusion-based AM techniques, according to
selected patterns. The use of these processing techniques required the introduction
of specific computer-aided tools in order to obtain the desired material distribu-
tion profile in a continuous and interconnected way throughout the entire geometry.
Varying architectural parameters such as fiber diameter, spacing between consecu-
tive fibers, layer thickness and deposition angle between layers, 3D scaffolds with
controlled porosity, pore shape and tailored mechanical properties have been ob-
tained [ 18 - 20 ]. In a recent study, Sobral et al. demonstrated how additive manu-
facturing techniques are suitable at modifying architectural features of the scaffold
with the aim of increasing mechanical stability and cell seeding efficacy [ 21 ]. Space-
filling fractal curves, such as Hilbert curves, have been also used in combination
with extrusion-based methods for the generation of internal architectures mimick-
ing bone gradient porosity [ 22 ].
Even if the use of regular lattice structures has lead to several advantages in terms
of modeling, fabrication, properties evaluation and prediction, they are not suited to
fully represent the complexity of heterogeneous natural tissues. To this aim, efforts
have been made in order to create more intricate internal architectures and/or to
find irregular ways to assemble the elemental cells. Thus, libraries of more complex
units have been fabricated while new packing approaches have been developed in
order to generate stochastically the anchors points of each unit element [ 23 , 24 ].
A totally different approach to obtain more realistic 3D models is based on the
reconstruction of the tissue (e.g. bone) morphology, starting from computer tomog-
raphy (CT) or other digital imaging data [ 25 - 27 ]. However, designing a faithful