Biomedical Engineering Reference
In-Depth Information
(Chew.et.al.,.2008)..In.addition,.aligned.electrospun.ibers.appeared.to.enhance.Schwann.
cell.maturation.more.than.the.randomly.oriented.ibers.did,.as.was.shown.by.the.upregu-
lation.of.the.myelin-speciic.gene..In.vitro.results.were.conirmed.by.the.in.vivo.studies.
in.which.anatomical.and.functional.measurements.showed.that.constructs.with.aligned.
polymer.ibers.signiicantly.enhanced.nerve.regeneration.in.17.mm.peripheral.nerve.gaps.
in.rats.over.those.of.randomly.oriented.ibers.(Kim.et.al.,.2008).
Micro-.and.nanoscale.topography.was.shown.to.play.an.important.role.in.neural.stem.
cell.differentiation..Yang.et.al..(2005).observed.that.the.mouse.neural.stem.cell.differentia-
tion.rate.might.depend.on.the.iber.dimension..The.differentiation.rate.on.nanoibers.300.
nm. in. diameter. was. twice. as. high. as. on. microibers. with. a. 1.5. µm. diameter.. However,.
these.results.on.the.effect.of.iber.diameter.on.neural.cell.differentiation.are.controversial..
Christopherson.and.his.colleagues.(2009).found.that.under.differentiation.conditions,.rat.
neural.stem.cells.stretched.multidirectionally.and.preferentially.differentiated.into.oligo-
dendrocytes.on.ibers.with.a.diameter.of.283.nm,.but.they.elongated.along.a.single.iber.
axis. and. preferentially. differentiated. into. neuronal. lineage. on. ibers. 749. nm. and. 1,452.
nm.thick..Despite.these.conlicting.results,.topographical.and.biological.cues.seem.to.be.
important.in.the.control.of.stem.cell.behavior.
Electrospinning. approaches. involving. blending,. coaxial. extrusion,. and. emulsion. spin-
ning. are. used. in. the. incorporation. of. bioactive. agents. like. proteins. and. growth. factors.
to. enhance. cell. attachment,. growth,. differentiation,. and. survival. of. cells. in. nerve. tissue.
engineering.applications..Incorporation.of.laminin,.a.neurite-promoting.basement.mem-
brane.protein,.to.a.synthetic.polymer.by.blending.was.reported.as.a.more.eficient.method.
to. produce. biomimetic. scaffolds. than. covalent. immobilization. and. physical. adsorption.
of. the. bioactive. agents. (Koh. et. al.,. 2008).. In. a. recent. study,. nerve. growth. factor. (NGF),. a.
common.neurotrophic.factor.involved.in.peripheral.nerve.regeneration,.was.incorporated.
in. poly(L-lactide-co-ε-caprolactone). ibers. by. emulsion. electrospinning. (Li. et. al.,. 2010)..
Pheochromocytoma.12.(PC12).cells,.which.differentiate.into.a.neuronal.phenotype.in.the.
presence.of.NGF,.were.used.in.a.study.where.NGF.was.released.from.ibrous.mats.for.a.
sustained.period,.revealing.its.bioactivity..A.glial.cell-derived.neurotrophic.factor.(GDNF),.
important.in.motor.neuron.survival,.was.entrapped.in.aligned.biodegradable.polymeric.
ibers.(a.copolymer.of.ε-caprolactone.and.ethyl.ethylene.phosphate.(PCLEEP)).(Chew.et.al.,.
2007)..An.in.vitro.release.proile.of.GDNF.showed.that.after.an.initial.burst.release.of.about.
30%,.the.remaining.GDNF.was.released.in.a.fairly.sustained.manner.for.almost.2.months.
Electrical. stimulation. is. another. tool. that. affects. neurite. extension.. Electrical. stimula-
tion.using.an.external.electrical.ield.and.an.electroconductive.polypyrrole.(PPy).ilm.was.
shown. to. enhance. neurite. extension. in. vitro. (Schmidt. et. al.,. 1997).. Xie. et. al.. (2009a). cul-
tured. DRG. explants. on. conductive. (PPy). core-sheath. nanoibers. electrospun. with. PCL,.
and. results. showed. that. upon. electrical. stimulation,. the. rate. of. neurite. extension. was.
enhanced.on.both.random.and.aligned.nanoibers.without.any.change.in.the.direction.of.
the.neurites'.extension..In.another.study,.PPy.was.deposited.on.electrospun.PLGA.ibers.
to.investigate.the.response.of.PC12.cells.(Lee.et.al.,.2009)..Upon.application.of.10.mV/cm.
on. PPy-PLGA. scaffolds,. PC12. cells. exhibited. 40-50%. longer. neurites. and. 40-90%. more.
neurite.formation.than.unstimulated.cells.on.the.same.scaffolds.
In.conclusion,.the.topography.of.nano/microibrous.scaffolds.closely.resembles.that.of.
the.natural.ECM,.and.this.is.an.important.factor.in.tissue.engineering..Considering. the.
architecture.of.longitudinally.oriented.nerve.tissue,.uniaxially.aligned.ibers.could.create.
an.appropriate.environment.for.guided.nerve.regeneration..The.use.of.the.aforementioned.
tools.with.aligned.ibrous.scaffolds.could.be.a.promising.approach.in.the.design.of.a.bio-
mimetic.substitute.for.nerve.regeneration.
