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Additive manufacturing of bone scaffolds
           minimal surfaces were more easily wetted with higher   lower than 74%. Beyond this critical  point,  the  solid
           permeability, leading to deeper cells into growth as well   phase turned disconnected.
           as more uniform cell distribution, as compared with a   Another  typical  mathematical  modeling  is  Voronoi-
           salt-leached scaffold with a random-pore architecture .   Tessellation  method, which constructs porous models
                                                        [69]
           Kapfer et al.  investigated two kinds of TPMS-based   using a  Voronoi diagram.  A typical scaffold design
                      [68]
           structure, including network solids and sheet solids. In the   principle  based on  Voronoi-Tessellation  method is
           network solids, the minimal surface constructs the solid/  depicted in Figure 5. In particular, a set of points (or seeds)
           void interface, whereas in sheet solids, porous solids are   are positioned randomly inside the design volume to fulfill
           constructed by inflating the minimal surfaces to sheets   a partition of the space in regions. Then, a thickness is
           with  a  predefined  thickness.  Finite  element  analysis   assigned to the edges of the partitioned regions to obtain a
           confirmed that the sheet solids possessed considerably   porous scaffold [79,80] . The design of porous structure based
           higher mechanical stiffness than that of network solids   on  Voronoi diagram could be traced back to Kou  and
           for identical volume fractions (Figure 4B and C) and   Tan [81,82] , where they first proposed to use Voronoi vertices
           Poisson’s ratio (Figure 4D). Moreover, the sheet solids   as the control points of a closed B-spline curve to create
           also exhibited higher material utilization and provided   a  convex-shaped cell.  Besides,  a  porous structure  was
           relatively more surface  area and pore  space for  cell   obtained by merging the adjacent  cells. However, they
           migration and activity.                             only studied the 2D pore structure. While Chow et al.
                                                                                                            [83]
           TPMS has been explored for its possibility to construct   organized Voronoi seeds in concentric circles and formed
           gradient,  heterogeneous,  hybrid, and irregular  porous   a 2D shape region. Subsequently, a 3D porous structure
                                  [38]
           structures.  Melchels  et al.  reported  that  the  design   was constructed by expanding the time dimension of the
           of a gradient porous structure can be constructed based   dynamic pattern in the third dimension of the 2D shape
           on  TPMS by adding  a linear function.  Feng  et al.    region.
                                                         [31]
           designed heterogeneous  porous scaffolds with non-  In recent years, researchers have conducted a more in-
           uniform threshold, period, and unit by combining TPMS   depth study on  Voronoi-Tessellation-based  scaffold
           and solid T-splines. In addition, Yang et al.  proposed   design and have achieved great progress. For example,
                                                [70]
           two CAD methods to prepare hybrid porous structures for   Fantini et al.  combined CAD 3D software Rhinoceros
                                                                         [84]
           biomimetic design purposes that combine different TPMS-  with its Plug-in Grasshopper  to design bone scaffolds
           based structures with given transition boundaries. Using   based  on  Voronoi-Tessellation  method.  This  work
           his approach, it is able to place TPMS-based substructures   successfully correlated to the input parameters, including
           on given 3D subspaces with perfect transitions to their   the  number of seeds, porosity, and  the  pore size  of
           adjacent substructures within a scaffold domain. A series   the structure . Gómez  et al.  proposed a bone-like
                                                                          [85]
                                                                                         [86]
           of multiscale  and multimorphology  porous scaffolds   trabecular structure design based on Voronoi-Tessellation
           were presented in their further studies [71-74] . For similar   principle. The seeds of Voronoi diagram were extracted
           goals, Yoo et al. [75-77]  combined a kind of distance field   from the micro-CT images of the trabecular bone. The
           with  TPMS-based functions to effectively  construct   obtained isotropic porous scaffolds were then perfectly
           pseudorandom porous scaffolds.  Yang  et al.  utilized   matched  the main histomorphometric  indices of nature
                                                 [78]
           coordinate transformation based on TPMS to construct   bone.  More  importantly,  the  final  properties  could
           an gradient and full irregular porous structure, extending   be  tailored  during  the  design  stage  by changing  the
           TPMS to irregular design areas. However, the stochastic   trabecular  separation  and thickness.  Wang  et al.  put
                                                                                                         [87]
           porous structure constructed by this method had porosities   forward a probability sphere method to generate random
                                                               seeds based on the  Voronoi-Tessellation.  In this study,
                                                               a scale coefficient K was introduced to control the pore
                                                               size and strut thickness, which successfully achieved the
                                                               balance between “irregularity” and “controllability.” As
                                                               a result, highly mimic scaffolds with porosities ranging
                                                               from 60% to 95% and pore size ranging from 200 to
                                                               1200 μm were designed precisely. In addition, a porosity
                                                               gradient ranging from 0.03 to 0.54 was also obtained. In
                                                               this regard, it is clear that Voronoi-Tessellation method
                                                               combines the advantages  of reverse modeling  method
                                                               and topology optimization method. It cannot only realize
          Figure 5.  A schematic  diagram showing the  scaffold  design   the bionic structure design of bone scaffold but also
          principle  based on  Voronoi-Tessellation  method  and as-built   optimize  the structure to achieve desirable properties,
          scaffolds .                                          such as porosity, permeability, and mechanical strength.
                 [87]
           6                           International Journal of Bioprinting (2019)–Volume 5, Issue 1
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