Biomedical Engineering Reference
In-Depth Information
were.prepared.by.electrospinning,.and.the.release.characteristics.were.investigated..They.
found.that.shikonin-loaded.as-spun.iber.mats.showed.an.initial.burst.release.followed.
by. a. gradual. release.. In. addition,. the. amount. of. shikonin. released. from. the. iber. mats.
increased.with.increasing.the.amount.of.PTMC.in.the.blends..This.could.be.due.to.the.
lower. diameter. of. PCL/PTMC. blend. ibers. at. a. ratio. of. 5:5,. giving. them. a. higher. sur-
face. area. to. release. a. larger. amount. of. drug.. Moreover,. PTMC. being. more. hydrophilic.
than.the.semicrystallized.PCL.resulted.in.an.increase.of.water.absorption,.and.thus.the.
ibers.easily.dissolved.in.the.medium..The.antioxidant.and.antibacterial.activities.of.these.
iber. mats. were. also. studied. for. use. in. biomedical. applications.. It. was. found. that. after.
being. subjected. to. a. high. electrical. potential,. the. biological. activity. of. these. iber. mats.
was.retained.
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23.3.3 Genes
The.major.goal.of.gene.therapy.is.to.reconstitute.a.missing.or.defective.gene.with.a.cor-
rect. copy. in. the. host. genome.
95
. This. can. be. achieved. by. introducing. the. missing. genes,.
promoting.expression.of.the.existing.genes,.or.stopping.diseased.gene.expression..Since.
naked. DNA. has. shown. low. transfection. toward. target. cells,. effective. delivery. of. the.
desired.genes.into.target.cells.is.possible.when.biocompatible.gene.carriers.are.utilized.
96,97
.
Electrospinning.techniques.have.been.used.to.fabricate.ibrous.scaffolds.for.genetic.mate-
rials.delivery..In.2003,.Luu.et.al..developed.electrospun.scaffolds.of.PLGA/PLA-PEG.block.
copolymers.loaded.with.pCMVβ.plasmid.encoding.β-galactosidase.DNA.
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.The.amount.of.
the.plasmid.released.was.as.high.as.80%.of.the.initial.load.of.DNA..The.PLGA/PLA-PEG.
ratio.affected.the.amount,.rate,.and.eficiency.of.DNA.release..Their.results.also.showed.
that.the.released.DNA.remained.intact,.even.when.passing.through.high.voltage.during.
electrospinning..Moreover,.the.released.DNA.could.transfect.the.preosteoblastic.cell.line,.
MC3T3-E1,.and.successfully.encoded.β-galactosidase.protein.in.vitro..However,.the.trans-
fection.eficiency.was.still.low..Since.the.gene.carriers.must.deliver.the.genetic.materials.
through. several. extra-. and. intracellular. barriers. to. reach. the. nucleus. of. the. target. cells,.
including.crossing.the.plasma.membrane,.surviving.the.acidic.and.degradative.endosom-
al-lysosomal. system,. traveling. to. the. nucleus,. and. releasing. the. genes. into. the. nucleus,.
the. direct. incorporation. of. the. plasmid. into. the. electrospun. iber. might. not. be. enough.
to. achieve. high. eficiency.. Apart. from. electrospun. ibers,. the. gene. carriers. commonly.
used. to. date. can. be. divided. into. two. categories:. viral. and. nonviral.
99
. Viral. vectors. have.
been.used.in.current.clinical.trials.mostly.because.of.their.innate.ability.to.overcome.the.
mentioned.obstacles,.thus.resulting.in.high.eficiency.of.gene.delivery..Retroviruses.and.
adeno/adeno-associated.viruses.are.regarded.as.the.most.effective.carriers.of.therapeutic.
genes.for.a.prolonged.gene.expression.period.
100
.Long-term.gene.expression.involves.inte-
gration.of.viral.genes.into.the.host.genome..Gene.delivery.using.the.viral.vectors.associ-
ated. with. electrospinning. was. recently. studied.. Coaxial. electrospinning,. a. setup. where.
an.aqueous.solution.containing.drugs,.proteins,.or.genetic.materials,.forming.the.inner.jet,.
is.coelectrospun.with.a.polymer.solution.forming.the.outer.jet,
101
.was.used.to.fabricate.a.
sustained.viral.gene.delivery.scaffold..Liao.et.al.
102
.were.among.the.irst.group.to.produce.
core-shell. ibrous. scaffolds. via. coaxial. electrospinning. to. eficiently. and. locally. deliver.
viral.vectors.into.mammalian.cells..They.found.that.close.to.90%.of.HEK.293.cells.were.
transfected.in.the.irst.2.weeks,.and.then.dropped.to.0%.in.the.following.weeks,.when.the.
cells.were.exposed.to.the.scaffold.supernatant..On.the.other.hand,.the.cells.seeded.directly.
onto.the.virus-encapsulated.scaffolds.expressed.a.high.level.of.transgene.expression.for.
over.1.month..This.indicated.the.prolonging.and.localizing.cell.transfection.ability.of.the.
