Computational Mechanobiology in Cartilage and Bone Tissue Engineering: From Cell Phenotype to Tissue Structure - Computational Modeling in Tissue Engineering - page 344

• The dissolution rate of biodegradable scaffolds should be optimised to match the
speed of differentiation and matrix synthesis by cells within the scaffold. The
dissolution rate can be modulated via the relative amounts of the components
that make up the biomaterial, which will in turn affect intrinsic properties such
as stiffness.
Alterations to the properties above likely affect the mechanical environment in
the scaffold and hence the mechanoregulation of biological processes. Due to the
multitude of design criteria and their strong coupling, mechanobiological model-
ling can contribute significantly to finding optimal scaffold properties or limiting
the number of physical prototypes to be tested. Provided the knowledge, efficiency
and resources in the future, this computational optimisation of scaffolds could be
envisaged routinely on a patient-specific basis to maximise clinical success and
stream-line the automated production process [ 56 , 72 ].
Bioreactors are a fundamental part of tissue engineering for two main reasons
[ 72 ]. First, one approach to tissue engineering involves cell biopsies, ex vivo
expansion and culture in a bioreactor to achieve desired tissue properties and
subsequent reimplantation. More indirectly, bioreactors bear significant relevance
for mechanobiological research. They present model systems in which environ-
mental aspects such as cytokine concentrations, medium composition, pH, oxygen
environment and mechanical loading can be much more tightly controlled than in
vivo.
Computational models can not only help in the design of scaffolds, but also
in the design of bioreactors and the choice of their operating parameters.
Several bioreactor designs exist that induce fluid flow in or around the scaf-
folds, such as direct perfusion, spinner flask or rotating wall bioreactors. Their
prime purpose is to enhance culture medium transport to provide the optimal
biochemical environment for the cells. However, fluid flow induced shear is a
potent mechanical stimulus that can influence the metabolic activity of the cells
or even their phenotype. Hence it has been suggested [ 72 ] that computational
fluid dynamics methods rather than trial and error should be used to establish
the flow conditions for the various bioreactor systems, scaffold architectures and
cell types. The same concept can of course be applied to related aspects of
bioreactor performance such as direct mechanical stimulation by deformation.
Other applications include the derivation of culture and rehabilitation protocols
derived from the analysis of in vivo conditions [ 13 ], the derivation of the
cellular environment from the macroscopic bioreactor input profiles [ 72 ], the
online integration of computational models into tightly monitored commercial
tissue culture systems to improve automated control and surgical planning [ 72 ]
and hence enable a more cost-effective and scalable approach to tissue
engineering. In the context of cartilage tissue engineering and bioreactor design
we wish to draw attention to the contributions by Raimondi et al. [ 93 ] and
Bjork et al. [ 7 ] in this topic for further information.