BIOMIMETIC MATRICES FOR INTEGRIN-MEDIATED CELL ADHESION - Biologically-Responsive Hybrid Biomaterials - page 246

nanopatterns were introduced to polymeric, metallic, and bioceramic surfaces,
results tend to show the enhancement of cell adhesion.
It is relatively easy to endow nano-features on polymeric surfaces because of
inherent material flexibility, as reviewed by many papers [78-81]. In particular,
Biggs et al. [82] used electron beam lithography to create nanoscale pits and
grooves on PMMA. They observed that the nanopit arrays disrupted the focal
adhesion formation and cellular spreading of human osteoblasts (HOBs) and the
FAK mediated activation of the ERK/MAPK signaling pathway (osteospecific
differentiation) in mesenchymal populations. However, HOBs cultured on 100
mm wide groove arrays increased integrin mediated adhesion formation and
cellular spreading, likely through α 5 β 1 integrin binding. In another study
Heydarkhan-Hagvall et al. [83] investigated the effects of human fibroblast
adhesion behavior on silicon surfaces with nano-post and nano-grate structure
modifications. While the integrin subunits α 5 β 1 and β 3 were all detected, β 3
exhibited stronger signals on nano-grates. Furthermore, paxillin and
phosphorylated FAK (pFAK) were observed as elongated and aligned on nano-
grates, as opposed to the small dot-like patterns at the cell-periphery exhibited on
nano-posts. This indicates that nano-grates may be more effective in inducing
human fibroblast adhesion and downstream signaling. In addition to influencing
protein adsorption through nanotopology, proteins can also be arranged in
clusters to modulate cell adhesion. Nanopatterning of FN with controlled size
and pitch against nonadhesive polyethylene glycol (PEG) surfaces led to the
controlled number of FN proteins within each adhesion site and cell adherance to
these nanopatterns with even distributions as compared to that on a glass control
[84].
Researchers and clinicians have also investigated the effects of
nanoroughness on metallic substrates. There are several ways to introduce
surface nanoroughness, including but not limited to plasma-spraying, grit
blasting, acid-etching, anodization or calcium phosphate coatings. For instance,
researchers have shown how Fbg [85] and FN [86] adsorption increased with
increasing nanoroughness of tantalum films. The positive effect of
nanostructures on protein adsorption [87] and osteoblast adhesion [88] was also
confirmed on the most commonly used bone implant, Ti. In contrast, Cai et al.
[89] reported that there were no significant differences between Fbg adsorption
on smooth and nano-modified Ti substrates. Thus, further investigation into the
effects of nano-modifications on protein adsorption and integrin-mediated cell
adhesion is warranted.