Computational Mechanobiology in Cartilage and Bone Tissue Engineering: From Cell Phenotype to Tissue Structure - Computational Modeling in Tissue Engineering - page 350

and Kelly [ 78 ]. While in uncharged tissues, fibres perpendicular to the loading
direction cause the highest stiffness in unconfined compression, fibres aligned with
the loading direction produce the highest initial stiffness values in charged tissues.
This is routed in the pre-stress of the collagen network due to the swelling pres-
sures induced by the fixed negative charges of the GAG molecules. None of these
studies, however, investigated potential collagen remodelling mechanisms during
bioreactor culture and their effect on the mechanical properties of the engineered
cartilage.
In a recent study from our lab we applied a newly developed collagen
remodelling algorithm [ 80 ] to test the hypothesis that structural changes to the
collagen network in response to loading could contribute to enhanced biome-
chanical properties of dynamically compressed cartilaginous constructs even in the
absence of biochemical differences between the free-swelling (FS) and dynami-
cally loaded (DL) groups [ 79 ]. Fifty-six days of bioreactor culture were simulated
during which proteoglycans and collagen were synthesised leading to a steady
increase in material parameters that was equal in both the FS and DL groups. The
collagen remodelling algorithm used [ 79 , 80 ] allowed for changes in the local
collagen orientation and its stress-free configuration (i.e. the transition from a
buckled fibre with insignificant stress contribution to a tensed cable like config-
uration with a high stress contribution where the transition point is called
recruitment stretch, Fig. 4 a) via a multiplicative decomposition of the deformation
gradient (Fig. 4 b). Collagen reorientation alone was predicted to lead to decreased
construct stiffnesses. Remodelling the stress-free configuration of the collagen
network increased swelling pressures and altered its state of pre-stress leading to
increased mechanical properties. Only when combining both mechanisms could
the increased Young's moduli, decreased Poisson's ratios and altered construct
geometries be predicted in accordance with experimental observations (Fig. 5 ).
These results provide support for the hypothesis that in addition to various
mechanisms such as cross-linking, a structural reorganisation of the collagen
network potentially contributes to enhanced mechanical properties, and provides
mechanistic insight into the effects of different structural phenomena [ 79 ].
The study further demonstrates how constitutive models can add insight to
experimental results via a theoretical decoupling of physical mechanisms.
5 Bridging the Gap: Multiscale Models
5.1 The Multiscale Approach
Extensive knowledge on biological processes and their dependence on mechanics
is being acquired at all relevant length scales from the biomolecular level up to the
tissue and organ level. One challenge is to data mine, integrate, present and distil
this huge amount of information and computational information technology is an