Kenneth E. Gonsalves, Craig R. Halberstadt, Cato T. Laurencin, Lakshmi S. Nair. Biomedical Nanostructures
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Osteoprogenitor, human bone marrow cells seeded on nanotopographies
less than 10 nm showed similar features of extending filopodia toward
nanostructures like fibroblasts [146]. Cells were seen to curl around
nanofeatures while maintaining their normal morphology and spreading on
flat control surfaces. Well-defined cytoskeleton with increased actin stress fibers
consisting of large networks of tubulin and vimentin were observed on
nanofeatures compared to the controls. Mesenchymal differentiation was
demonstrated by the increased amount of osteocalcin and osteopontin
expression by these cells on nanotopographies compared to the controls in a
21-day culture pe riod [146]. With the PLLA-PS blends nanotopographic
features were created using spin cast having the nanodimensions of 329 nm
height or depth [147]. Human fetal osteoblasts adhesion was higher on
nanostructures than the flat control surfaces, and nanoislands registered
highest adhesion in all the cases studied. Cell adhesion was also dependent on
many nonbiological cues including surface chemistry and wettability [147].
Human fetal osteoblasts on randomly distributed nanoisland topography with
varying heights of 11, 38, and 85 nm also exhibited similar cellular behavior
like fibroblasts previously discussed [148]. Osteoblasts showe d filopodia
projections and lamellipodia spreading in order to sense the nanotopography.
Osteoblasts seeded on 11-nm-high islands showed significantly enhanced
Nanotopography: nanoisland height
Cell behavior
13 nm
24 nm
35 nm
95 nm
Enhanced adhesion both initial and
long term
Well-developed cytoskeleton
Enhanced initial adhesion
Poorly developed cytoskeleton
No change in adhesion than flat control
Poorly developed cytoskeleton
Reduced adhesion
Poorly developed cytoskeleton
13 nm
24 nm
35 nm
95 nm
FIGURE 10.8 Human fibroblast behavior on nanotopographic features created by
polymer demixing of polystyrenepoly(4-bromostyrene) blends. Fibroblast exhibited
enhanced adhesion, proliferation, and well-developed cytoskeleton on 13-nm nanois-
lands, and with an increase in feature height, a decrease in all these above said
properties were observed.
286
BIOMEDICAL NANOSTRUCTURES
spreading, proliferation, signal trans mitting structures such as vinculin protein,
actin stress fibers, and typical bone marker alkaline phosphatase (ALP)
expression compared to the larger nanoislands or flat controls.
Dalby et al., studied human endothelial behavior on nanoislands of varying
heights 13, 35, and 95 nm and observed size-dependent cellular behavior [41].
Endothelial cells also showed the largest cellular response on 13 nm with well-
spread morphology and well-define d cytoskeleton than larger nanoislands and
flat controls. Human monon uclear bloo d cells, platelets, fibroblasts, and
endothelial cells were tested for their behavior on nanotopographies consisting
of nanoislands of 95 nm [149]. No significant difference was observed in blood
response to these nanoislands and flat control indicating minimum immuno-
logical difference. Fibrob lasts were characterized by rounded morphology,
reduced proliferation, and not well-developed cytoskeleton. Endothelial cells
attained the characteristic curved morphologies in response to nanoislands.
10.3 CONCLUSIONS
Different nanofabrication methods need to be explored to pattern large surface
areas with ease, precise control over geometries and shapes in a commercially
viable manner. Many of these nanotopographical features including surface
chemistry and properties should be further developed in order to control cell
function at cellbiomaterial interfaces. Such an understanding will help to elicit
desired cellular functions including preferential adhesion, migration, prolifera-
tion rate, and expression of specific cell phenotypes that can help in the design of
a new generation of tissue engineering scaffolds and biomedical implants.
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