Biomedical Engineering Reference
In-Depth Information
Cell sheet technology has been developed by Okano's group tar-
geting for the regeneration of cell-dense tissues.
65
Culture surfaces
are grafted with poly(
N
-isopropylacrylamide) and serve as tempo-
ral supports for a monolayer culture. The thermo-sensitive nature
of culture surfaces allows for harvest of intact cell sheets with
maintaineddifferentiatedfunctions,attributabletothepreservation
of cell surface proteins, cell-cell interactions, and deposited ECM.
Three-dimensionaltissuescouldbeconstructedbystackingindivid-
ual cell sheets together, free of scaffold support.
65
,
66
24.3.1.2 3D polymeric scaffolds
Three-dimensional gels of ECM proteins remain one popular cul-
ture system for epithelial cells, especially for glandular epithelial
cells.
67
,
68
For example, breast epithelial cells cultured in Matrigel
form cystlike spheroids with a central lumen and distinct apical
and basolateral polarity, recapitulating certain structural features
of glandular epithelium
in vivo,
whereas malignant breast epithe-
lialcells only formrandom aggregates in 3D culture. These 3D mod-
els can be used in the mechanistic studies of tumor initiation and
progression.
69
A broad range of 3D polymeric scaffolds have been devel-
oped for hepatocyte culture, as exemplified in Table 24.1. Among
them, microcapcules and hydrogels are of particular interest,
where hepatocytes grow as aggregates or spheroids with inti-
mate cell-cell contacts. Chia
et al.
reported a microencapsulation
procedure for hepatocytes using complex coacervation in a physio-
logical environment.
70
The microcapsules of functional hepatocytes
are
∼
150
μ
m, with a 2
∼
3
μ
m outer layer of polyanions, and an
inner layer of modified positively charged collagen to provide suit-
able cell-matrix support. The microcapsules are permeable to small
molecules up to albumin, allowing e
cient exchange of nutrient,
oxygen, growth factors, and metabolites, while preventing attack
by immunoglobulins of the immune systems. Their applications in
hepatocyte transplantation and BLAD warrant future study.
Hydrogelsareattractivematricesforcellculture,duetotheirtis-
suelike properties such as hydrophilicity and mechanical integrity
tosofttissues.Polyethyleneglycol(PEG)-basedhydrogelshavebeen
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