Computational Mechanobiology in Cartilage and Bone Tissue Engineering: From Cell Phenotype to Tissue Structure - Computational Modeling in Tissue Engineering - page 343

Instead of focussing on variability, other studies take a subject specific
approach. A bone remodelling algorithm based on open system thermodynamics
was applied to simulate the pattern of bone mineral density in the proximal tibia in
response to gait loading [ 87 ]. A subject specific geometry and load, derived from
gait analysis, were used. The predicted bone density distribution showed excellent
qualitative and quantitative agreement with the subject specific pattern measured
by X-ray absorptiometry. In another study, Wolff's law was ''inverted'' to estimate
the loading history of a murine vertebral body via an optimisation approach based
on a set of unit loads applied to a subject specific model of a murine vertebral
body, the internal structure of which was modelled based on lCT scans [ 21 ].
Based on the assumption that bone tissue remodels such that the strain energy
density approaches a target value and that the tissue is loaded uniformly, the
dominant load case could be extracted both in direction and magnitude. The strain
energy density in the trabecular architecture remained highly non-uniform nev-
ertheless. The review article by Geris et al. [ 38 ] includes a discussion of patient
specificity and variability in in silico approaches.
4 Scaffolds in Bone and Cartilage Repair
4.1 Computer Aided Design of Scaffolds and Bioreactors
Scaffold design is constrained by a large number of design criteria that often
compete. This competition implies that there is some optimum design that rep-
resents the best compromise between the various requirements. Relevant aspects to
be considered in scaffold design include:
• The material has to be non-toxic, biocompatible, sterilisable, manufacturable
into arbitrary shapes accommodating patient specific defect geometries, and
possess biologically favourable surface properties.
• Considerations regarding the intrinsic mechanical properties of the material
include compliance-matching with the host tissue, sufficient strength during
implantation, cellular response to substrate stiffness (see Sect. 2 ), and expected
deformations that potentially act as external stimuli.
• The scaffold architecture can serve as a template to guide tissue architecture,
including anisotropy [ 30 ]. The porosity is linked to the apparent properties of
the scaffold and is therefore mechanically constrained such that the scaffold
maintains its structural integrity. However, higher porosities are favourable
for cell seeding and proliferation, tissue ingrowth and mass transport.
Porosity also affects the permeability and hence fluid velocities during
seeding as well as mechanical loading. Depending on the target tissue, the
pore architecture and its interconnectivity has to be suitable for vasculari-
sation of scaffold and tissue.