Biomedical Engineering Reference
In-Depth Information
20.4 Nanotopography and Focal Adhesion Formation
That. material. topography. and,. in. particular,. nanoscale. features. can. affect. integrin-
mediated. cell. adhesion. is. evident. from. studies. with. fabricated. topographical. features..
Nanotechnology.aims.to.create.and.use.structures.and.systems.in.the.size.range.of.about.
1-500.nm.covering.the.atomic,.molecular,.and.macromolecular.length.scales..A.range.of.
methods.exists.for.the.generation.of.topographical.nanoscale.features,.including.chemi-
cal.vapor.deposition,.polymer.phase.separation,.colloidal.lithography,.photolithography,.
and.electron.beam.lithography.(EBL),.to.name.but.a.few..For.a.full.review.of.the.method-
ology. for. nanoscale. fabrication. technology. in. 2006. see. Betancourt. and. Brannon-Peppas.
(Betancourt.and.Brannon-Peppas.2006)..Of.these.techniques,.however,.EBL.methodologies.
have.increasingly.been.employed.to.fabricate.complex,.regular,.and.high-resolution.nano-
structures.for.biological.assays.(see.Figure.20.3).
EBL.relies.on.the.emission.of.a.beam.of.electrons.that.is.raster.scanned.across.a.surface.
covered. with.a.sensitive.ilm. termed.a.resist,.selectively. removing.either. exposed.(posi-
tive.resist).or.nonexposed.(negative.resist).regions.of.the.resist.to.form.a.desired.pattern..
Currently,. the. lowest. x-y. resolution. obtainable. with. this. technology. lies. in. the. 5-10.nm.
range..Here.a.positive.resist.has.been.exposed.to.form.a.hexagonal.coniguration.of.pits.
The.general.protocols.for.nanomanufacturing.require.high.resolution.and.throughput.
coupled.with.low.cost..With.respect.to.biological.investigations,.nanotopographies.should.
occur.across.a.large.surface.area.(ensuring.repeatability.of.experiments.and.complete.pat-
terning. of. implant. surfaces),. be. reproducible. (allowing. for. consistency. in. experiments),.
and.preferably,.be.accessible.(limiting.the.requirement.for.specialized.equipment).(Wood.
2007).. The. extent. to. which. nanotopography. inluences. cell. behavior. within. an. in. vitro.
environment.remains.unclear,.and.investigation.into.this.phenomenon.is.still.ongoing..A.
question.being.asked.in.the.ield.of.medical.device.manufacture.is.whether.nanofeatures.
offer.any.relevant.stimuli.to.cell.populations.in.vivo.and,.if.so,.whether.implants.could.be.
fabricated.to.include.these.topographical.structures..It.follows.then.that.fabricated.model.
surfaces. with. deined. topographies. are. of. great. experimental. importance. in. engaging.
with.such.issues.in.vitro.and,.further,.may.facilitate.early.studies.examining.the.cellular.
reaction.to.nanostructures.in.vivo.
The.processes.that.mediate.the.cellular.reaction.to.nanoscale.surface.structures,.however,.
are.not.well.understood.and.may.be.direct.(Dalby.et.al..2007;.a.direct.result.of.the.inlu-
ence.of.the.surface.topography).or.indirect.(where.the.surface.structure.has.affected.the.
Electron gun
Electron beam
Resist
S4700 10.0 kV 5.1 mm × 30.0k SE(U)
1.00 µm
Substrate
Figure 20.3
(See companion CD for color igure.)
.Schematic.of.electron.beam.lithographic.nanofabrication.
