Computational Mechanobiology in Cartilage and Bone Tissue Engineering: From Cell Phenotype to Tissue Structure - Computational Modeling in Tissue Engineering - page 345

4.2 Tissue Differentiation in Scaffolds
4.2.1 Optimisation of Scaffold Properties
Significant efforts have been directed at engineering bone and cartilage or
enhancing the natural reparative processes by a variety of interventional methods.
Scaffolds implanted into osteochondral defects have been used to enhance repair
tissue quality but a major unknown are the ideal scaffold properties. The earliest
attempt to determine optimal mechanical properties of a scaffold using a com-
putational mechanobiological model was for the repair of an osteochondral defect
[ 56 ]. The main assumptions of the model were that MSC differentiation as well as
cell proliferation and apoptosis were determined by a combination of fluid flow
and shear strain [ 91 ] and that cell migration could be modelled as a diffusive
process. By systematically varying the Young's modulus and the permeability of
homogeneous scaffolds it could be shown that optimal values for these parameters
exist, with both higher and lower values leading to decreased amounts of cartilage
tissue. This result was due to the differential influence of fluid flow and shear strain
on cell differentiation. To further enhance repair, i.e. reduce the amount of fibrous
tissue and stop the subchondral bone from progressing into the cartilage zone, a
bilayered scaffold with inhomogeneous properties was then optimised. The osse-
ous part of the scaffold was modelled as homogeneous while the properties of the
chondral part were depth dependent. The study found that the optimal scaffold
should have a stiffness that decreases with depth from the superficial to the deep
zone and a permeability that increases with depth, i.e. has its minimum at the
articular surface. Given the inhomogeneous properties of articular cartilage this
scaffold has to a certain extend biomimetic qualities. The study closes with the
remark that scaffolds optimised for the in vitro setting may not be well suited for
the in vivo environment and vice versa.
A similar approach has been followed to investigate design parameters in bone
scaffolds by Byrne et al. [ 14 ]. Tissue differentiation was again regulated by fluid
flow and shear strain [ 91 ], while cellular activities were modelled using the lattice
approach [ 90 ]. Tissue differentiation inside a bioresorbable scaffold with regular
geometry typical for 3D printing techniques was simulated under low and high
loading conditions varying three key design variables: Young's modulus, porosity
and dissolution rate. The authors were able to determine unique combinations of
these parameters that maximised bone formation depending on the loading
condition. Especially under high loading conditions the initial porosity and dis-
solution rate had to be chosen conservatively as to not compromise the structural
integrity of the scaffold. High porosities, a medium dissolution rate and a high
stiffness gave the optimal results under low loading conditions. This suggests that
scaffold manufacturing should be tailored towards the loading conditions at the
implantation site.
Scaffold based tissue repair of critical sized defects is often hindered by
inadequate vascular supply resulting in a degraded scaffold core and peripheral