Biomedical Engineering Reference
In-Depth Information
947 lm. The difference in bone architecture indicates that the selection of the
biomaterial with a certain pore size depends on the location to where it is going to
be transplanted.
4.2 Biomaterial Stiffness
Even though most cells in vivo attach to and proliferate on rather soft matrices, in
vitro research today is mainly performed on stiff surfaces such as glass and plastic
[
14
]. However, the influence of matrix stiffness on many cellular processes, for
example, migration [
39
,
40
], adhesion [
41
,
42
], cell shape [
40
,
42
,
43
], and pro-
liferation [
44
], has already been verified. Furthermore, many recent publications
confirm that matrix stiffness determines the fate of MSC and consequently their
differentiation [
45
,
46
]. The results of these experiments provide the evidence
that MSC are able to sense the stiffness of their local microenvironment [
47
].
Discher et al. stated that cells respond to the stiffness of their surrounding envi-
ronment by adjusting their adhesion and their cytoskeleton [
138
]. Their feedback
to matrix stiffness is probably a change in the expression of integrins, cadherins,
and cytoskeletal proteins [
43
].
It has been found that hMSC respond in vitro differently to elasticities similar to
the in vivo tissue stiffness of brain (0.1-1 kPa), muscle (8-17 kPa), and nascent
bone (more than 34 kPa) [
45
]. In vitro hMSC expressed neurogenic, myogenic,
and osteogenic key markers when cultivated in the same medium, but on
biomaterials with the stated elasticities. Directed differentiation was demonstrated
without the addition of expensive growth factors [
46
]. Furthermore, Engler et al.
[
45
] stated that soluble growth factors tend to be less selective than matrix stiffness
regarding cell differentiation. MSC were cultured on a soft matrix (0.1-1 kPa) in
growth medium for either 1 or 3 weeks. Then either myogenic or osteogenic
differentiation medium was added. A decrease in gene expression of myogenic or
osteogenic markers was only observed during the initial week of cultivation. After
one week, MSC committed to the lineage specified by the substrate stiffness. These
results emphasize that the surface stiffness of biomaterials has a significant
influence on the determination of cell fate [
46
]. But by which mechanism do MSC
sense the biomaterial stiffness and how do they transmit the information into
differentiation signals? A short answer to this question will be given in
Sect. 5
.
4.3 Microscale and Nanoscale Topography
It is widely accepted that the topography of a biomaterials surface determines the
biologic reaction. The topography of matrices influences the cell adhesion [
48
],
orientation, and differentiation. However, these effects seem to be cell-dependent.
Different cell types have been observed to show a preference for either a smooth or
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