Biomedical Engineering Reference
In-Depth Information
on.the.mammalian.cells.covered.with.an.aqueous.PEG.phase.to.deliver.genetic.materials.
selectively.
12.3 DynamicSubstratesforControllingCell
AdhesionandGeneratingCocultures
Recent.advances.in.the.ability.to.engineer.surface.properties. of.substrates.have.allowed.
researchers.to.dynamically.modulate.the.interactions.between.cells.and.the.substrate.sur-
face.in.real.time.using.an.external.trigger.such.as.voltage,.heat,.or.light..These.techniques.
can.be.used.for.controlling.the.adhesion.and.motility.of.cells.and.for.the.sequential.pat-
terning.of.multiple.cell.types.
12.3.1 Voltage-Responsive Substrates
Electrochemical. transformations. available. on. SAMs. can. alter. the. physicochemical. prop-
erties. of. the. surface. in. situ,. thereby. being. utilized. to. dynamically. control. cell. adhesion.
and.migration..For.example,.Yousaf.et.al..developed.SAMs.of.which.the.terminal.groups.
can. be. electrically. switched. to. allow. the. immobilization. of. cell-adhesive. molecules. 36 . In.
this. approach,. an. inert. and. nonadhesive. monolayer. of. a. hydroquinone. group. against. a.
background. of. tri(ethylene. glycol). groups. on. a. gold. substrate. was. used.. Electrochemical.
oxidation.of.a.hydroquinone.group.to.the.corresponding.benzoquinone,.which.is.reactive.
to.cyclopentadiene.by.the.Diels-Alder.reaction,.was.used.to.selectively.immobilize.a.cell-
adhesive. peptide. ligand. conjugated. with. the. diene.. This. dynamic. substrate. was. used. to.
prepare.cocultures.of.two.different.cell.types.by.allowing.a.irst.population.of.cells.to.attach.
to.a.patterned.monolayer,.and.then.activating.a.second.pattern.for.attachment.of.a.second.
population,. as. well. as. to. create. a. cell. migration-based. assay.. Another. example,. based. on.
electrochemical.transformation.of.SAMs,.has.been.carried.out.by.Jiang.etĀ al. 37 .They.adopted.
the.electrochemical.desorption.of.an.ethylene.glycol-terminated.SAM.on.a.gold.substrate.to.
induce.cell.migration.onto.the.SAM-desorbed.area..Recently,.they.extended.this.approach.
to.pattern.multiple.types.of.cells.within.microluidic.channels. 38
Kaji.et.al..developed.a.surface.patterning.technique.based.on.an.electrochemical.method.
that.enables.the.localized.immobilization.of.cells.under.physiological.conditions. 39-41 .This.
technique.used.a.microelectrode.to.electrochemically.generate.an.oxidizing.agent.HBrO,.
which. acts. on. a. heparin-. or. albumin-coated. substrate,. initially. antibiofouling,. to. render.
these.regions.cell.adhesive..Since.this.technique.can.be.conducted.under.cell.cultivation.
conditions,. it. facilitated. the. stepwise. immobilization. of. multiphenotype. cell. arrays. and.
the.in.situ directional.navigation.of.cell.migration.(FigureĀ 12.4)..Also,.since.the.patterning.
procedure.requires.only.small.numbers.of.electrodes.and.a.small.dry.battery,.it.was.read-
ily. applicable. to. miniaturized. and. semiclosed. systems. such. as. microluidic. devices. and.
tubing.scaffolds. 42-45
12.3.2 Light-Responsive Substrates
Photochemistry.is.also.useful.for.dynamically.modulating.interactions.between.cells.and.
the.substrate.surface..For.example,.Nakanishi.et.al..used.a.SAM.of.silanes.having.a.pho-
tocleavable.2-nitro-benzyl.group. 46,47 .In.this.approach,.the.entire.surface.of.the.SAM.was.
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