Biomedical Engineering Reference
In-Depth Information
transmembrane.proteins,.and.ilopodia—tend.toward.the.nanoscale..Furthermore,.extra-
cellular. supporting. tissues. also. typically. present. an. intricate. network. of. cues. at. the.
nanoscale,.composed.of.a.complex.mixture.of.nanometer-size.(5-200.nm).pits,.pores,.pro-
trusions,.and.ibers.(Karuri.et.al..2004;.Brody.et.al..2006),.suggesting.a.regulatory.role.for.
these.structures.in.vivo.
The.use.of.lithographic.and.etching.techniques.derived.from.the.silicon.microelectronic.
industry. has. facilitated. investigation. into. the. intricate. role. of. nanoscale. topography. on.
all. aspects. of. cellular. (including. bacterial). behavior—importantly,. adhesion,. activation,.
and.differential.function..The.focus.of.this.chapter.is.on.recent.in.vitro.studies.consider-
ing.cellular.interactions.with.fabricated.nanoscale.topographies,.with.an.emphasis.on.the.
modulation.of.integrin-mediated.cellular.adhesion.and.how.nanotopographical.modiica-
tion.may.inluence.cellular.function.
20.2 Cell Material Interactions
During. the. processes. of. tissue. development. and. maintenance,. cells. encounter. a. varied.
spectrum. of. topographies,. ranging. from. macro-. (bone,. ligament,. or. vessel. morphology),.
micro-. (cellular. morphology,. protein. aggregates). to. nanoscale. features. (collagen. band-
ing,.molecular.conformation,.and.ligand.presentation).(Curtis.and.Riehle.2001;.Curtis.and.
Wilkinson.2001),.each.of.which.has.the.potential.to.inluence.cell.behavior.and.functional-
ity.. An. early. study. by. Carrel. and. Burrows. in. 1911. showed. that. cells. were. responsive. to.
shape.cues.(Carrel.and.Burrows.1911),.and.over.the.past.decade,.the.effects.of.microtopog-
raphy. have. been. well. documented. (McNamara. et. al.. 2011).. Nanobioscience. as. a. ield. has.
emerged.from.the.observation.that.cells.interact.with.nanoscale.features.in.vivo..For.exam-
ple,.the.basement.membrane.possesses.a.complex.mixture.of.nanoscale.pores,.protrusions,.
and.ibers,.features.that.may.have.a.regulatory.role.in.tissue.development..In.the.corneal.
epithelium.of.the.Macaque.monkey.(Abrams.et.al..2000),.the.basement.membrane.nanoto-
pography.consists.of.a.porous.membrane.with.a.network.of.cross-linked.ibers,.with.the.
pores.averaging.72.nm.and.the.ibers.77.nm.in.diameter..A.complex.nanoscale.trabecular.
meshwork.is.also.observed.in.the.human.cornea.(Gong.et.al..2002).consisting.of.a.network.
of.ibrous.beams.covered.by.trabecular.endothelial.cells.
Critically,.evidence.is.gathering.on.the.potential.advantages.of.nanotopographical.modi-
ication.in.the.function.of.next-generation.biomimetic.materials,.with.an.aim.to.modulate.
the.cellular.response..Interaction.with.nanotopographies.has.been.shown.to.alter.cell.mor-
phology.(Dalby.et.al..2003a),.adhesion.(Biggs.et.al..2009a,b),.motility.(Berry.et.al..2004),.pro-
liferation.(Dalby.et.al..2002b,c),.endocytotic.activity.(Dalby.et.al..2004a),.protein.abundance.
(Kantawong.et.al..2009a,b),.and.gene.regulation.(Dalby.et.al..2002d),.and.responsiveness.
has.been.observed.in.a.diverse.range.of.adherent.cell.types.including.ibroblasts.(Dalby.
et. al.. 2002b,c,d),. osteoblasts. (Price. et. al.. 2003),. osteoclasts. (Webster. et. al.. 2001;. Geblinger.
et.al..2010),.endothelial.cells.(Dalby.et.al..2002b,c),.smooth.muscle.cells.(Thapa.et.al..2003),.
epithelial.cells.(Andersson.et.al..2003a,b),.and.epitenon.cells.(Gallagher.et.al..2002)..This.
is. intriguing. from. a. biomaterials. perspective. as. it. demonstrates. that. surface. features.
approaching.the.dimensions.of.a.single.molecule.can.inluence.how.cells.respond.to,.and.
form.tissue.on,.biomaterials..To.date,.the.smallest.feature.size.shown.to.affect.cell.behavior.
is. 10.nm. (Dalby. et. al.. 2004b),. which. illustrates. the. importance. of. considering. the. topo-
graphical.cues.deliberately.or.inadvertently.presented.to.cells.during.in.vitro.culture.and.
