Biomedical Engineering Reference
In-Depth Information
2.5.5.1 Morphology and Response of Endothelial Cells
Previous studies have reported that endothelial cells (ECs) can respond viably to
surface topographical features in the micrometer, submicrometer and nano-
meter ranges. For example, Palmaz et al. 56 found that on NiTi surfaces discon-
tinuities at the microscopic scale influenced the conformation and motional
dynamics of migrating ECs. Migration speeds increased (up to 64%) on surfaces
with gratings ranging from 3 to 22 mm compared with flat control surfaces.
Patterning of Ti surfaces involving periodic arrays of gratings, with widths and
spacings ranging from 750 nm to 100 mm using a plasma-based dry etch
technique, have been used to study EC adhesion, proliferation and morphology. 57
In this work, it was observed that ECs on nanoscale patterned Ti surfaces were
oriented and displayed enhanced cell function compared with smooth Ti surfaces
and random nanostructured Ti surfaces. A number of articles discussing a variety
of substrates have reported that the line grating geometry results in enhanced
adhesion and orientation of ECs. 58-60 A frequent comment emanating for this
sort of study suggests that the line grating is analogous to native endothelium.
However, there have also been a number of reports which indicate that such
patterns result in reduced cellular proliferation. The reason for this observation is
unclear at the present time and clearly requires further investigation.
The effect of nano-island geometry, especially for experiments involving
polymer surfaces, on EC behavior has also been extensively investigated.
Interestingly, both increased and reduced spreading of ECs on such patterns
have been reported. 61,62 In overall terms these studies highlight the fact that
quite slight changes in feature height produce large changes in EC behavior. In
addition, surface chemistry clearly has an effect on EC response because there is
significant variation in cellular response associated with the various polymer
mixes employed in the research.
A limited number of studies on the response of ECs to nano-posts have been
reported. For example, Kim et al. 63 demonstrated that nano-post PEG surfaces
fabricated using capillary lithography enhanced the focal adhesion of ECs. This
result was attributed simply to an increase in material surface area and
adhesion sites for cells. Recently, Zawislak et al. 64 showed the development of
ECs on 3D nano-post silicon surfaces with a depth of 10 mm, a periodicity of
6 mm and a diameter of 0.15 mm. In a sub-confluent layer, the cells impaled
themselves on the pillar to the extent that even some of the cell nuclei were
penetrated by the pillar tips.
Given the great importance of new biomaterials in the world of stent tech-
nology it is not surprising that there has been a concentrated effort to study the
behavior of ECs on substrates that display random nanostructured features.
For example, increased EC function (including collagen and elastin synthesis)
has been reported on nanostructured Ti compared with nano-smooth Ti. 65
Similarly, Peng et al. 66 showed significantly enhanced EC proliferation and
secretion of (prostaglandins) PGI 2 on nano-tubular TiO 2 surfaces formed via
anodic oxidation Generally speaking most studies strongly indicate enhanced
EC function on such surfaces.
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