Biomedical Engineering Reference
In-Depth Information
3.1.3 Example: Cell Differentiation
An important measure of the cell-material interaction is the maintenance of cell
phenotype or the capability of progenitor cells to differentiate into the tissue-
respective phenotype, e.g. for an applications in bone, that mesenchymal pro-
genitor cells differentiate into osteoblasts. Therefore, phenotype-specific gene
markers or proteins must be assessed. These assessments have to be performed at
different time-points to allow a statement regarding the expression kinetics. The
time-point of measurement is critical here, since the up-regulation of mRNA
markers and protein concentrations have their own optima [ 73 , 164 ]. The
expression kinetics are influence by the material. The time-points of maximal and
also of overall expression can be shifted. Thus by investigating one time-point
only, it is not possible to make any useful statement. This may be another reason
for the contradictionary in vitro and in vivo results [ 62 ].
So far, unfortunately, a systematic evaluation comparing in vitro and clinical
data is still missing. The types of influences that a material evoke are broad and
limitations of in vitro tests may vary largely between the type of influence
(for instance surface topography or drug) and parameter that is measured in vitro.
However, it must be noted that, especially for such complex processes like dif-
ferentiation, the current in vitro systems might be far too simple to expect a good
correlationship between in vitro performance and clinical success.
4 Future Perspectives: Advanced In Vitro Systems
Mimicking the In Vivo Niche
In vitro and in vivo systems are hard to compare due to the differences in their
complexity. In vitro systems are designed to be as simple as possible, i.e. there is
only one cell type which is cultivated under two-dimensional conditions, on tissue
culture treated polystryrene (TCPS) and with an optimized culture medium con-
taining partly overdosed but mostly very underdosed factors. In contrast, in vivo
there is always more than one cell type involved and cells act in a three-dimen-
sional environment in a dynamic fashion surrounded by interstitial fluids and
extracellular matrix (ECM). It is this artificial, for the cells, pathological envi-
ronment to which cells adapt and respond. For cell lines this pathological adaption
may even be more striking. It is in this context that the biocompatibility of
materials is currently evaluated in vitro. The fact that cells are in a pathological
situation which is related in hardly any aspect to the in vivo counterpart probably
represents the predominant reasons for the limitations in translating in vitro
findings into preclinical applications. So far, no final solutions have been presented
and the bridging of the gap between in vitro and in vivo is still a matter of
further research. However, various efforts have been undertaken which are very
promising.
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