Biomedical Engineering Reference
In-Depth Information
investigation of contact guidence effects an extensive modelling framework has
been introduced by Barocas and Tranquillo [ 3 ]. It relies on mixture theory to
capture the biphasic nature of the soft tissue equivalents under consideration and
accounts for collagen alignment in response to anisotropic deformation, sub-
sequent cell alignment, i.e. contact guidance, and the resulting anisotropic traction
exerted by the cells onto the ECM as well as their anisotropic migration.
The described models are taking a major step towards the coupling of a cell's
response to its external as well as internal mechanical environment. They have the
potential of facilitating a better understanding of the cell's interaction with its
environment, including intrusive measurement tools. This is crucial for the ade-
quate interpretation of experimental results and for examining cell rheology.
Several aspects might be put onto the research agenda: The incorporation of actual
signalling pathways into the models will not only increase their predictive capa-
bility, but also allow the investigation of pathological or experimental (e.g. drug
related) inhibition of those very pathways. Further, while the models described in
this section link mechanics to cellular remodelling and are capable of rationalising
a number of experimental observations, the link between biology and mechanics
needs to be extended.
3 Stem Cell Differentiation During In Vivo Regeneration
3.1 Testing Mechanoregulation Hypotheses In Silico
The idea that mechanics affects tissue differentiation has been discussed in the
scientific community for a long time [ 89 , 95 ]. By incorporating hypotheses
regarding mechanoregulated tissue differentiation into computer simulations of
regenerative events (such as fracture healing) that exhibit well defined and
repeatable temporal and spatial patterns of tissue differentiation with alternative
healing paths depending on mechanical stimulation, these hypotheses can be
corroborated or rejected by comparing the in silico predictions to the experimental
observations. These approaches therefore constitute a valuable tool in the
assessment of potential biophysical regulators of tissue differentiation and may
have specific relevance for the incorporation of biophysical stimulation into bio-
reactor designs for tissue engineering applications. Similarly, such corroborated
hypotheses might serve to form the basis for the evaluation of the mechanical
environment in scaffolds for tissue engineering (see Sect. 4 ) The ultimate goal of
tissue engineering is to replace or repair damaged tissues in vivo. Quantitatively
evaluating the in vivo environment and its effects on the tissues during regener-
ation therefore has direct relevance to tissue engineering itself.
In accordance with the scope of this chapter we restrict this overview on
relatively recent work where theories regarding mechanoregulated tissue differ-
entiation have been tested using modern simulation techniques. Specifically we
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