Computational Modeling of Mass Transport and Its Relation to Cell Behavior in Tissue Engineering Constructs - Computational Modeling in Tissue Engineering - page 94

design was proposed to deliver VEGF in a spatial concentration gradient where it
is able to both initiate and spatially control angiogenesis. Regulating spatial VEGF
presentation increased hindlimb blood flow which was reflected in a reduced
incidence of limb necrosis.
Other more detailed numerical models of in vivo regeneration processes could
equally well be applied for the rational design of controlled delivery systems [ 40 ].
Such models have the added advantage of testing the efficacy of a certain treatment
strategy (such as controlled-delivery systems) in silico, hence helping researchers
to identify the most promising strategies and having the potential to significantly
reduce experimental costs [ 41 ].
6 Discussion and Conclusions
Proper functionalizaton of carriers used for TE applications, requires a profound
understanding of the mechanisms that drive solute transport to and from the active
cell units. These solutes can be as small as oxygen, essential for cellular nutrition,
or as large as protein complexes, which allow cells to communicate with each
other or probe their environment [ 122 ]. The cellular actions they can elicit range
from basic cell survival and division to the organized patterning of cells into
tissues (i.e., morphogenesis).
Mimicking the normal in vivo solute transport environment of a cell and
optimization of culture conditions is complicated by the various mechanisms
which underlie these transport processes. We have shown that this variability can
be induced by differences in molecular size between solutes, differences in syn-
thesis and uptake of solutes by the cell, interactions at a cell level between various
nutrients and metabolites (but also signaling molecules [ 4 , 106 ]), solute interac-
tions with the surrounding matrix and many others. Systems that involve such high
degrees of complexity can however greatly benefit from mathematical modeling,
as we have shown in this chapter.
Choosing an optimal model and setting an appropriate level of detail is strongly
determined by the extent of construct remodeling that is taking place, the avail-
ability and type of experimental data, and spatial resolution [ 107 ]. Focus in this
chapter has been mainly set on single scale (continuum) models which is ascribed
to their abundant availability and their low computational costs. If we however
want to recreate interactions at multiple levels of organization with respect to
space and time, more attention should be attributed to the integrative properties of
the model [ 114 ], a strategy that has been defined in literature as multiscale
modeling. Crucial to the success of a multiscale modeling framework, is to provide
a consistent cross-scale linkage interface between the models at each biological
level [ 23 ]. We have shown the importance of such an interface in the context of
diffusive transport within TE carriers, by providing a means to correlate micro-
structural matrix properties to solute diffusion rates using for example a volume
averaging technique [ 129 ].