Biomedical Engineering Reference
In-Depth Information
Jeong.et.al..2005)..However,.to.create.truly.ine.structure.in.capillary.beds,.it.is.likely.that.the.
initial.seeding.of.cells.and.signaling.molecules.will.require.exact.placement..Additionally,.
3D. scaffolds. are. critical,. as. virtually. all. functional. tissues. and. organs. are. complex. 3D.
structures..The.scaffold.itself.must.be.of.appropriate.materials.and.the.cell.types.must.also.
be.appropriate.and.localized.to.the.proper.locations,.not.homogeneously.seeded..Integrated.
scaffolds.with.heterogeneous.structure.can.be.created.with.the.resolution.of.laser.direct-
write.techniques..For.this.application,.their.versatility.with.a.range.of.materials,.and.the.
ability.to.conduct.ablative.material.removal.work.without.drastic.alteration.of.the.setup.is.
a.major.advantage.
Mechanical. considerations. are. simply. the. irst. hurdle. for. vascularization. in. tissue.
engineering..Angiogenic.signaling.molecules.are.also.vital.(Kulkarni.et.al..2004)..Vascular.
endothelial. growth. factor. (VGEF). has. been. the. best. studied. of. these,. but. it. alone. is. not.
suficient.to.create.complete.vascular.networks..A.complex.combination.of.molecules.are.
necessary,. in. an. ordered. sense,. both. spatially. and. temporally.. Placental. growth. factor,.
platelet-derived. growth. factor-BB,. Angiotensin. 1,. and. transforming. growth. factor. beta.
have. all. been. used. (Teebken. and. Haverich. 2002;. Stegemann. and. Nerem. 2003;. Martin.
et.al..2004;.Freed.et.al..2006;.Gong.and.Niklason.2008)..Studying.the.interaction.of.these.
signaling. factors. and. their. optimal. levels. and. timing. proves. to. be. dificult.. As. the. list.
of. chemical. interactions. continues. to. grow. for. just. this. one. facet. of. tissue. creation,. new.
methods. of. studying. cell-cell. interactions. en. masse. become. critical.. Laser. direct-write.
allows.for.precise.placement.and.coculture.of.any.cell.type,.and.allows.for.simplistic.and.
idealized. spatial. organization. of. the. cells.. Thus,. spatial. cell-cell. interactions. between.
neighboring.cell.groups.and.involved.signaling.can.be.studied.in.a.way.that.eliminates.
many. complications. found. in. holistic. living. systems.. Investigation. in. isolation. of. each.
molecular. signaling. mechanism. will. yield. precise. information. on. its. function. and.
characteristics..Indeed,.single.cell.transfers.may.give.unprecedented.levels.of.detail.on.the.
phenotypic.effects.on.speciic.cells.for.any.number.of.situations.and.applied.stimuli,.let.
alone.just.signaling.molecules.(Blau.et.al..2001;.Chen.et.al..2001;.Jain.2003;.Levenberg.et.al..
2005;.Pérez-Pomares.and.Foty.2006;.Kolakowski.et.al..n.d.).
Microbeads.have.been.transferred.intact.by.the.LIFT.process.(Palla-Papavlu.et.al..2010)..
Microbeads. can. provide. a. unique. environment. for. a. contained. cell. population,. allow-
ing. control. of. local. chemical. and. mechanical. effects.. Similar. to. seeding. cells. hetero-
geneously,. separate. microbeads. can. be. printed. in. close. proximity,. allowing. paracrine.
communication. between. cell. cultures,. but. preventing. any. wide-scale. redistribution. of.
said.separate.cultures..Tissue.spheroids.without.microbead.containment.can.easily.fuse.
together. (Mironov. et. al.. 2009).. Both. avoiding. and. encouraging. fusion. will. have. their.
applications.(Even-Ram.et.al..2006;.Guilak.et.al..2009;.Winer.et.al..2009;.Pek.et.al..2010)..
The.ability.to.isolate.separate.cultures.while.allowing.for.biomolecule.diffusion.will.be.
important. for. maintaining. printed. shapes. as. well. as. furthering. the. study. of. paracrine.
communication..Laser.direct-write.will.allow.for.the.accurate.and.repeatable.transfer.of.
both.microbeads.and.tissue.spheroids.for.the.assembly.of.tissues.and.for.investigating.
core. biological. questions.. It. has. been. shown. that. the. differentiation. of. MSCs. depends.
on.the.mechanical.properties.of.their.environment..MSCs.tended.to.express.osteogenic.
transcription.factors.when.in.environments.of.relative.stiffness.and.myogenic.and.neu-
ral. transcription. factors. in. environments. of. moderate. and. lower. stiffness,. respectively.
(Dawson.et.al..2008;.Guilak.et.al..2009;.Winer.et.al..2009)..Additionally,.MSCs.have.been.
shown.to.halt.differentiation.when.cultured.on.a.medium.that.replicates.the.elasticity.of.
bone.marrow..When.presented.with.a.stiff.substrate.they.again.reentered.the.cell.cycle..
Mechanical.properties.and.loading.experienced.by.a.cell.are.then.critical.to.control.over.
