Biomedical Engineering Reference
In-Depth Information
hepatocyte. functions. and. behaviors.. It. is. made. up. of. mostly. collagen. I,. IV. (Kent. et. al..
1976),.laminin.(Friedman.et.al..1985),.ibronectin.(Ramadori.et.al..1987),.and.heparan.sul-
fate.proteoglycans.(Bissell.et.al..1987,.Grant.et.al..1989)..Collagen.and.other.ECM.glyco-
proteins. promote. cell. attachment. of. primary. hepatocytes. forming. monolayers.. For. the.
regeneration.of.this.specialized.tissue,.an.aligned.mesh.of.ECM.is.required..Three.types.
of.surfaces.are.in.contact.with.these.specialized.and.highly.polarized.epithelial.tissues.
commonly.found.in.organs.such.as.liver,.pancreas,.and.kidney:.a.basal.surface.contacting.
the. ECM,. a. lateral. surface. for. cell-cell. interactions,. and. an. apical. surface. that. faces. the.
lumen..It.is.found.that.designing.the.precise.structure.of.the.ECM.and.apical.surfaces.into.
the.scaffolds.is.of.critical.importance.to.successful.regeneration,.in.order.to.avoid.having.
the. cells. undergo. apoptosis. or. generate. a. lumen. at. a. region. of. contact. with. other. cells.
(Bryant.and.Mostov.2008).
To.induce.the.interaction.between.the.basal.surface.of.the.liver.and.ECM.ibers,.Bettinger.
et. al.. (2009a). used. native. collagen. ilms. as. model. for. creating. nanotopography. on. APS..
Replica-molding.of.nanotopographic.features.was.shown.to.have.improved.initial.attach-
ment,.spreading,.and.adhesion.of.primary.rat.hepatocytes.(see.Figure.22.4)..Some.result.
also. indicated. that. the. nanotopographic. features. helped. reduce. albumin. secretion. and.
urea.synthesis,.indicating.strongly.adherent.hepatocytes..These.results.suggest.that.these.
engineered.substrates.can.function.as.synthetic.collagen.analogues.for.in.vitro.cell.culture.
Flat
Nano
PDMS
Collagen
Figure 22.4
Cell-substrate.interactions.shown.with.hepatocytes.cultured.on.APS.substrates.exhibited.a.rounded.morphol-
ogy,. compared. to. those. cultured. on. PDMS. and. collagen. substrates. exhibiting. a. more. lattened. morphology..
Hepatocytes.appear.to.have.extended.ilopodia.on.nanotopographic.2DAHP-1G,.lat.2DAHP-1T,.and.collagen.
substrates.(see.white.arrows)..Hepatocytes.induced.wrinkling.of.PDMS.substrates.(see.white.arrows.and.inset)..
(From.Bettinger,.C.J..et.al.,.
Tissue Eng. Part A
,.15,.1321,.2009a.)
