Biomedical Engineering Reference
In-Depth Information
We analyzed the number of adherent cells and found an increased number of cells on the
VN-incubated hydrogels. This effect was also found for the unpatterned, smooth hydrogels;
after VN-incubation a very small but significant number of cells were able to adhere to the
PEG surface. In
Figure 10
these results are depicted; comparing smooth and patterned
hydrogels with and without VN-incubation.
It can be seen that compared to the effect of topography alone, the VN-incubation alone was
less effective in enabling cell adhesion. Remarkably, the effect of VN on cell adhesion was
only evident at early time points; after 24 hours the enabling effect was completely lost.
Finally, a striking synergistic effect was observed from the combination of VN-incubation
and topography; the number of adherent and spread cells was larger than the sum of the
individual contributions (Schulte et al., 2011). Taking into account the apparent difference in
the effect of topography and VN with time, we tentatively conclude that the cell adhesion
protein VN facilitates the initial cell adhesion, while the adhesion-enabling effect of surface
topography becomes dominant at longer times and is necessary for the development of
durable and stable adhesion complexes.
3. Conclusion
Hydrogels are of high relevance for several biomedical applications. We have described the
fabrication of a hydrogel system based on poly(ethylene glycol) and evaluated the potential
of this PEG-based gel as a patternable biomaterial. PEG-based polymers are of great
importance as biomaterials for applications in cell and tissue engineering, as coating of
implants or biosensors, and as drug delivery systems. In particular, PEG coatings have been
used to minimize surface biofouling by plasma proteins to create surfaces that are
“invisible” to cells. Cell biological studies with murine fibroblasts (NIH L929) confirmed the
expected non-adhesive nature of the smooth hydrogel surfaces and furthermore ruled out
any toxic effect of the material. Alterations of the mechanical properties could easily be
achieved by varying the crosslinking density.
The most striking result from our studies is that the very popular and versatile PEG
biomaterial is not cell-repellent per se. Only when the surface of the bulk PEG hydrogels is
smooth it is anti-adhesive to cells, and this applies to all hydrogels we have investigated
with a stiffness ranging from 0.1 to 1 MPa. However, we have discovered that on the same
PEG hydrogels when decorated with micropatterns of topography, cells are able to adhere
and spread. We have explored several underlying biochemical, biophysical and
biomechanical factors that could attribute to this phenomenon and found that these factors
do have an effect indeed, and notably the combination of these parameters, e.g. protein
adsorption, surface topography and substrate compliance, work together to enable cell
adhesion to the intrinsically anti-adhesive PEG biomaterial.
More specifically, three investigated PEG-based hydrogels with different stiffness were all
cell anti-adhesive when smooth. However, in combination with topography, the softer gels
were clearly more attractive for the cells; on softer gels with the same pattern geometry,
significantly more cells adhered and spread than on the intermediate or stiffer gels. It seems
that the compliance of the softer gels enables the cells to 'squeeze' into the grooves, although
the cells apparently deform their own cytoskeleton rather than the topographic features.
We also discovered that a slight but significant amount of the ECM-protein Vitronectin is
able to adsorb to the PEG surface and that this leads to an increase in initial cell adhesion
during the first 4 hours of cell culture. However, this effect rapidly falls off. The effect of
