W. Richard Bowen and Nidal Hilal 4
W. Richard Bowen and Nidal Hilal 4
W. Richard Bowen and Nidal Hilal 4
- No tags were found...
Create successful ePaper yourself
Turn your PDF publications into a flip-book with our unique Google optimized e-Paper software.
7.2 ENgINEERINg THE ECM FOR PRObINg CELL SENSINg 207<br />
polymers cannot be completely ruled out. Consequently, an alternative way<br />
for fast <strong>and</strong> low cost of fabrication of nanoscale topographic features has<br />
been sought through the use of colloidal lithography. Monodispersed <strong>and</strong><br />
nanosized colloids made using wet chemistry techniques are commercially<br />
available. They can self-assemble into a monolayer on a substrate, with the<br />
spacing between each tailored by their surface charge or functional linker<br />
groups. The resulting colloid assembly is effectively a ‘photoresist’ pattern<br />
whose lateral dimensions are determined by the colloid size <strong>and</strong> spacing.<br />
Using this approach, nanocolumns of 160 nm height, 100 nm in diameter<br />
<strong>and</strong> 230 nm spacing have been produced in a bulk poly(methyl methacrylate)<br />
(PMMA) polymer [53, 54]. In comparison to the non-structured control,<br />
nanocolumns reduced focal adhesions of cells, but significantly increased<br />
density of filopodia formation. As discussed earlier, filopodia formation is<br />
associated with focal complexes, indicating the involvement of nanotopographic<br />
features on integrin cluster formation.<br />
The fact that many of the ECM proteins are present as nanofibres is<br />
driving intensive research on engineered nanofibres as replacements for<br />
ECM components. Carbon nanofibre compactions have been investigated<br />
for osteoblast culture with potential application as orthopedic/dental<br />
implants [55]. When compared with using conventional carbon fibres<br />
(diameter �100 nm), osteoblasts proliferate faster <strong>and</strong> deposit more extracellular<br />
calcium (indicating osteoblastic bone formation) on the carbon<br />
nanofibre compactions (diameter �100 nm). In other studies, synthetic<br />
<strong>and</strong> natural polymeric nanofibres have also long been regarded as promising<br />
analogues of the ECM. Here, a vast selection of well-established<br />
methods can be used to tailor their chemistries to match those found in<br />
the native ECM. To produce the polymeric nanofibres themselves, electrospining<br />
has become perhaps the simplest <strong>and</strong> most efficient technique for<br />
producing materials which can be assembled into 2D <strong>and</strong> 3D non-woven<br />
fibrous mesh (see review by Pham) [56]. Interestingly, cell culture on these<br />
nanofibre matrixes demonstrated better attachment <strong>and</strong> increased proliferation<br />
compared to that on substrates made from larger size fibres.<br />
Nanofibre meshes have also been found to stimulate cells to develop<br />
phenotypical behaviour [57, 58]. For example, NIH 3T3 fibroblasts <strong>and</strong><br />
normal rat kidney cells grown on a polyamide nanofibre matrix displayed<br />
in vivo-like morphology <strong>and</strong> breast epithelial cells on the same matrix<br />
underwent morphogenesis into multicellular spheroids [58].<br />
All the above-mentioned examples provide evidence which suggest that<br />
nanotopography has a significant influence on cell adhesion, cytoskeletal<br />
organisation <strong>and</strong> morphogenesis. However, the mechanisms involved are<br />
poorly understood: We do not know whether the less well-defined lateral<br />
dimensions of nanoisl<strong>and</strong>s made by either polymer mixing or colloidal<br />
lithography play any significant role in cellular behaviour; the nanofibre<br />
matrix may provide a large surface to volume ratio structure that could