Biomedical Engineering Reference
In-Depth Information
synthetic matrix.
103
An enhanced co-culture effect on hepatocyte
function was observed, imposed by the 3D microcapsule environ-
ment.Furthermore, biochemicallassaysrevealed an importantrole
of TGF-
β
1 regulation on the functional improvement. This finding
motivated the development of a simplified co-culture mimic, 3D-
microfluidic cell culture configuration of only hepatocytes via
in
situ
controlled release of active TGF-
β
1 from gelatin microspheres.
5
Cell-cell interaction can also be regulated by the modulation of cell-
matrix interaction.
95
Controlledtemporal/spatialpresentationofsolublefactorsin3D
matricesisessentialtotheengineeringofmore
invivo
-likemicroen-
vironments for hepatocyte differentiation and functions. The recent
decade has seen tremendous progress in the development of con-
trolled release technology.
4
Integration of this technology with scaf-
fold material design and fabrication technology will certainly aid in
the development of tissue-engineered liver tissue constructs. A few
pioneer studies demonstrated an improved survival rate in hepa-
tocyte transplantation by incorporating microspheres into porous
scaffolds to deliver hepatotrophic factors
104
and vascular endothe-
lial growth factor.
105
24.3.3
Biomechanical Issues
Encouraging epithelial cells to achieve polarity depends a lot on
the physical environment in which the cells are cultured. Cultur-
ing hepatocytes on stiff plastic or glass encourages the cells to
assumeaspreadingmorphologyastheyareexertingforcestomatch
the stiffness of their substrate.
49
They also lose polarity. Polarity
can be regained by culturing hepatocytes on a softer substrate, for
example, Matrigel,
106
to promote a more rounded morphology and
encourage cell-cell contact formation. A sandwich configuration, as
previously presented, of a porous membrane placed on top of a
hepatocytemonolayeroncollagenI-coatedplastic,wherebiochemi-
calandbiomechanicalcuesaregiventoboththebasalandtheapical
layer, is also ableto promote polarity.
6
Scaffolddesignandscaffoldmaterials,bothnaturalandsynthetic
ECM, provide a range of controllable parameters for regulation of
the biomechanical microenvironment presented to cells. Natural
type I collagen can be gelled at various concentrations and pHs to
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