Biomedical Engineering Reference
In-Depth Information
In.light.of.recent.studies.of.surface.properties.of.scaffolds,.the.signiicance.of.surface.pat-
terning.has.become.more.evident,.and.has.brought.increased.emphasis.on.its.use.as.a.tool..
Recently,. the. inluence. of. microscale. and. nanoscale. topographic. features. on. hepatocyte.
function. in. engineered. scaffolds. (Bettinger. et. al.. 2009a). has. been. investigated.. Together.
with.substrate.stiffness,.the.two.features.are.known.to.govern.cell.behavior.(Discher.et.al..
2005)..The.need.for.new.therapies.based.on.engineered.tissues.and.in.vitro.systems.(Bhatia.
and.Chen.1999,.Desai.2000,.Khademhosseini.et.al..2006).has.spurred.dramatic.advances.in.
microluidics.and.fabrication.technologies.over.the.past.decade.(Jo.and.Beebe.1999,.Quake.
and.Scherer.2000,.Whitesides.and.Strook.2001)..Numerous.methods.have.been.developed.
and.adapted.into.the.fabrication.process.of.micro-.and.nanopatterned.scaffolds.and.have.
created.patterned.scaffolds.that.have.demonstrated.great.potential.in.tissue.engineering.
Microscale.and.nanoscale.technologies.present.a.powerful.array.of.tools.for.addressing.
many.of.the.challenges.in.tissue.engineering.(Andersson.and.van.den.Berg.2004)..A.core.
element.of.these.advances.is.based.upon.microelectromechanical.systems.(MEMS),.which.
are.extensions.of.techniques.used.in.the.semiconductor.industry,.controlling.features.at.
length. scales. <1.μm. to. >1.cm. (Whitesides. et. al.. 2001).. In. addition,. micro-. and. nanoscale.
technologies. enable. an. unprecedented. ability. to. control. the. cellular. microenvironment.
in. culture. and. to. miniaturize. assays. for. high-throughput. applications.. The. emergence.
of.techniques.such.as.soft.lithography.to.fabricate.microscale.devices.without.expensive.
“clean.rooms”.(Whitesides.et.al..2001).has.enabled.the.application.in.biomedical.systems..
Soft.lithography.is.capable.of.controlling.the.topographic.and.spatial.distribution.of.mole-
cules.and.thereby.controls.placement.of.cells.on.a.patterned.surface.(Khademhosseini.et.al..
2003,.Suh.et.al..2004)..Soft.lithographic.and.conventional.photolithographic.methods.can.be.
used.to.fabricate.microluidic.channels.and.scaffolds.for.tissue.engineering.conveniently,.
rapidly,. and. inexpensively. (Whitesides. et. al.. 2001,. Walker. et. al.. 2004).. Microfabrication.
technology.has.been.used.for.tissue.engineering.in.part.because.of.the.superior.spatial.res-
olution.for.forming.critical.structures.such.as.capillaries,.in.comparison.with.traditional.
scaffold.fabrication.techniques.such.as.casting/porogen.leaching.(Murphy.et.al..2002),.gas.
foaming.(Harris.et.al..1998),.and.3D.printing.(Giordano.et.al..1996).
Pioneering. work. by. the. Grifith,. Bhatia,. Toner. laboratories. irst. explored. microscale.
technologies. as. a. platform. for. tissue. engineering.. More. recently,. microluidic. bioreac-
tors.were.seeded.with.endothelial.cells.(Kaihara.et.al..2000,.Borenstein.et.al..2002,.Leclerc.
et.al..2003,.King.et.al..2004).and.hepatocytes.(Powers.et.al..2002,.Leclerc.et.al..2003,.2004),.
and.microcontact.printing.was.utilized.to.enable.precise.control.over.heterotypic.cell-cell.
interactions.governing.hepatocyte.function.in.the.liver.(Bhatia.et.al..1999).
Others. have. also. employed. lasing. techniques. for. microfabrication. to. help. modify. cell.
behavior,. such. as. the. work. by. Tiaw. et. al.. on. changing. the. water. contact. angle. by. vary-
ing. the. micropattern. created. using. a. different. laser. (Tiaw. et. al.. 2005),. and. the. work. by.
Engelmayr. et. al.. recapitulating. the. in. vivo. environment. for. heart. tissue. regenerating.
through. laser. micromachined. biodegradable. scaffolds. that. have. mechanical. properties.
comparable.to.physiological.tissues.(Engelmayr.et.al..2008;.see.Figure.22.2).
22.2.3 electrospun Nanofiber Scaffolds
Electrospinning. is. a. technique. that. enables. the. production. of. nanometer-scale. ibers. to.
form. continuous,. nonwoven,. interconnected. nanoiber. scaffolds. that. closely. mimic. the.
native.extracellular.matrix.(ECM).composed.of.type.I,.II,.and.III.collagen.ranging.from.50.
to.500.nm.in.diameter.(Barnes.et.al..2007)..A.wide.variety.of.polymer.blends.ranging.from.
completely.natural.to.completely.synthetic.polymers.may.be.electrospun.to.create.scaffolds.
