Biomedical Engineering Reference
In-Depth Information
Recent. studies. have. conirmed. the. existence. of. cells. residing. in. niches,. unique. to. the.
tissues.and.organs.in.which.they.reside,.that.contain.highly.ordered.microarchitechtures,.
cellular. compartmentalization,. and. arrangement. 4 . Cells. sense. each. other. by. direct. con-
tact. in. a. process. in. which. cell. surface. receptors. (e.g.,. cadherins). detect. the. cell. surface.
receptors. of. neighboring. cells.. Cell. to. cell. contact. can. be. used. to. regulate. a. variety. of.
biological.processes,.such.as.cell.proliferation,.differentiation,.and.migration..Also,.cells.
signal.each.other.through.small.molecules.such.as.hormones.as.well.as.larger.molecules,.
which. are. mostly. made. of. proteins. such. as. chemokines,. cytokines,. and. growth. factors..
Such.molecules.typically.interact.with.cells.through.surface.receptors,.and.different.cells.
exhibit.unique.types.of.surface.receptors,.thereby.interacting.with.speciic.signaling.mol-
ecules..The.ECM.that.provides.three-dimensional.(3D).scaffold.or.2D.surface.with.which.
cells.interact.is.also.important.in.signaling.cells..The.ECM.is.often.comprised.of.proteins.
such.as.ibronectin.and.collagen,.as.well.as.polysaccharides.such.as.hyaluronic.acid.(HA)..
Through.interacting.with.the.ECM,.cells.are.provided.with.an.environment.to.which.they.
can.anchor.and.generate.tissues.
Recently,. emerging. technologies. at. the. interface. of. engineering. and. materials. science.
have.resulted.in.a.number.of.new.approaches.to.control.the.various.aspects.of.the.cellular.
microenvironment. 3,5-7 .The.merger.of.microfabrication.and.advanced.biomaterials.may.be.
useful.to.recreate.many.of.the.complex.features.to.create.in.vitro.microenvironments.with.
the.ability.to.effectively.direct.cell.behavior..For.example,.surface.patterning.can.be.used.to.
control.cell-substrate.and.cell-cell.interactions..To.control.the.interaction.with.substrates,.
techniques.such.as.lithography.and.surface.modiication.have.been.integrated..Through.
these.modiications,.properties.such.as.cell.adhesion.can.be.controlled.by.depositing.cells.
on. adhesive. regions. or. controlling. the. topography. of. surfaces.. Furthermore,. to. control.
the. interactions. of. cells. with. surrounding. cells,. various. patterned. coculture. techniques.
have.been.utilized..These.techniques.have.been.successful.with.controlling.the.homotypic.
and.heterotypic.cell-cell.interactions.in.vitro..Also,.microluidic.devices.have.been.used.to.
control.the.presentation.of.soluble.molecules.to.cells..Such.devices.provide.a.number.of.
advantages,.including.reduced.sample.volumes.and.costs.compared.to.conventional.mac-
roscale.systems..Moreover,.microluidic.channels.can.be.used.to.perform.high-throughput.
experimentation.and.to.control.cell-soluble.factor.interactions,.enabling.the.presentation.
of.soluble.factors.in.a.highly.controllable.manner.
This.chapter.highlights.the.recent.advances.of.microfabrication.technologies.that.can.be.
used.to.control.the.cellular.microenvironment.in.vitro..These.applications.of.microscale.
engineering.may.be.of.great.beneit.to.the.future.of.regenerative.medicine,.and.success.will.
be.highly.dependent.on.successes.in.both.tissue.engineering.and.stem.cell.differentiation..
These.suggest.that.the.development.of.technologies.to.achieve.the.desired.outcome.will.
hopefully.shorten.the.time.required.for.the.translation.of.these.techniques.to.the.clinic.
12.2 SurfacePatterningforControllingCellAdhesion
Most.of.the.techniques.used.in.the.generation.of.cellular.microenvironments.have.evolved.
from. semiconductor. fabrication. processes.. Thus,. planar. patterning. of. cellular. microen-
vironments.has.been.studied.more.in.comparison.with.3D.systems..Much.of.in.vitro.cell.
biology.studies.have.been.performed.on.planar.surfaces.by.using.microwell.plates,.culture.
lasks,. or. Petri. dishes,. since. they. are. convenient. for. investigating. cellular. responses. to.
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