Biomedical Engineering Reference
In-Depth Information
While. changes. in. cytoskeletal. organization. have. been. recognized. as. a. consequence.
of. altered. substrate. nanotopography,. the. mechanism. responsible. for. this. has. yet. to.
be. elucidated.. Curtis. et. al.. assessed. whether. surface. cues. left. any. temporary. marks. on.
ibroblast. cells. cultured. on. CL-fabricated. 160.nm. nanocolumns.. TEM. images. depicted.
nanocolumns.forming.indentations.on.the.cells'.surface,.and.the.authors.noted.that.this.
imprinting. extended. internally. into. the. cell,. as. well.. An. anti-integrin. alpha. 1. antibody.
was. used. to. reduce. cell. attachment. to. the. substrates.. A. nanopatterned. surface. further.
hampered.cell.adhesion.compared.to.that.of.a.planar.polycarbonate.control..This.seemingly.
indicates.the.presence.of.a.separate,.non-integrin-related.cellular.mechanism.that.guides.
cell.attachment.(Figure.8.3c;.Curtis.et.al..2006).
8.2.2.4 Nanoimprint Lithography
In. nanoimprint. lithography. (NIL),. a. resist. layered. on. the. surface. to. be. modiied. is.
stamped. with. a. nanopatterned. master. mold.. This. initial. step. takes. advantage. of. the.
glass. transition. temperature,. whereby. surpassing. this. critical. point. results. in. the. con-
version.of.the.thermoplastic.resist.to.a.viscous.luid.(Chou.et.al..1996)..Consequently,.the.
resist. now. contains. an. imprint—more. speciically,. a. thickness. contrast. to. the. original.
relief..Residue.removal.to.extract.the.desired.topography.can.be.performed.via.etching.
away.the.stamped.areas.on.the.resist..The.conventional.two-step.approach.can.be.con-
solidated.into.a.single.step.with.the.use.of.a.hybrid.mask-mold..After.applying.the.stamp.
to. a. resist,. the. entire. complex. undergoes. UV. light. exposure,. and. then. is. subsequently.
dipped.into.a.solution.to.remove.parts.in.the.resist.where.an.imprint.was.made.(Cheng.
and.Guo.2004;.Figure.8.3d).
As.observed.by.Yim.et.al.,.bovine.pulmonary.artery.smooth.muscle.cells.(SMCs).seeded.
onto. PMMA. and. poly(dimethylsiloxan). surfaces. of. nanogratings. (350.nm. line. width,.
350.nm. depth,. 700.nm. spacing). displayed. an. elongated. morphology. and. alignment. in.
a. parallel. fashion. not. observed. on. a. lat. substrate.. This. outcome. notably. correlated.
with.cell.behavior.in.vivo..However,.lower.BrdU.expression.in.SMCs.was.noted.in.the.
presence.of.nanopatterns,.attributing.decreased.proliferative.capacity.to.nanogratings..
Finally,. a. wound. healing. assay. demonstrated. the. strong. inluence. of. nanopatterns.
on. cell. migration,. with. SMCs. realigning. themselves. with. the. grating. axis. a. mere. 2.h.
postwounding.(Yim.et.al..2005)..In.another.study,.Johansson.et.al..cultured.adult.mouse.
sympathetic. and. sensory. ganglia. on. Matrigel
®
-coated. silicon. wafers. with. grooves.
and.ridges.(300.nm.depth,.100-400.nm.widths,.100-1600.nm.spacing)..Axons.preferred.
elongating.on.the.latter—notably.at.the.edges.of.these.elevations..Contact.guidance.was.
shown.to.depend.on.a.combination.of.axonal.and.nanofeature.dimensions;.for.example,.
grooves.and.ridges.of.100.nm.solely.guided.the.thinnest.axons.(Johansson.et.al..2006).
Nanopillars. (40-80.nm. diameter,. 150.nm-1.μm. height,. 100.nm. pitch). imprinted. onto.
tissue. culture. polystyrene. (TCPS). plates. (and. further. elongated. in. situ. via. adjustments.
to. demolding. temperature). were. seeded. with. human. foreskin. ibroblasts.. These. cells.
exhibited.inhibited.spreading,.greater.localization,.and.a.rounded.morphology,.unlike.on.
conventional.lat.TCPS,.where.they.had.wider.surface.distribution.and.possessed.ilopodia..
The. authors. thereby. attributed. the. hindrance. of. cell. spreading. to. the. high. aspect. ratio.
of. the. fabricated. nanopillars.. No. signiicant. improvement. in. cell. adhesion. following. O
2
.
plasma.treatment.to.minimize.surface.energy.(increase.hydrophilic.nature.of.the.substrate).
implied. that. physical. topography. seemed. to. impact. cell. adhesion. more. so. than. that. of.
chemical.factors.at.the.nanoscale.level.(Hu.et.al..2010).
