Biomedical Engineering Reference
In-Depth Information
• From single to multiple cell types. Recently, there have been many attempts to
address this issue. On the one hand, different mature cells types are cultivated in
the same culture, either completely mixed or separated via membranes. On the
other hand, obtained knowledge from stem cell research leads to the awareness
that an in vitro mixture of progenitor cells in different states of differentiation
and sometimes dedicated to different phenotypes yields more significant results
than single cell types (e.g. [
132
]). If a material is placed in a multi-cell-type
environment, each cell interacts with another in a synergistic way which is
crucial for tissue formation in vivo and in particular for tissue repair and tissue
homeostasis. The various cell types mutually affect cell proliferation, state of
differentiation, and functionality of other cells, either directly via membrane-to-
membrane contact or indirectly via released factors [
41
,
109
,
116
,
147
]. If a
material is placed in such a multi-cell- type environment, different cell types
will adhere to the surface and will thereafter compete for the space. The selected
cell-type composition should depend on the target application of the implant
material. In the case of materials used in a bone environment, key cell types may
include mesenchymal progenitor cells, osteoblasts, osteoclasts, fibroblasts and
endothelial cells, whereas for a topical application of a material, fibroblasts,
keratinocytes and endothelial cells are probably the key players. The cell type
with the strongest competitive force will finally prevail at the material surface
and will probably determine which kind of tissue is formed at the surface. The
material surface characteristics strongly affect the competitive force based on
cell proliferation and cell migration, which may occur cell-type-dependently as
shown by Vrana and co-workers [
142
]. The competitive force can be determined
by seeding different cell types on the material of interest and subsequently
evaluating the change in cell number of each cell type as a function of the
presence of the other cell type(s). Furthermore, the effect on the state of dif-
ferentiation of each of the different cell types might also be measured by
assessing cell-type-specific marker proteins [
89
,
151
].
• From 2D to 3D. In current cell culture biomaterial evaluations, single cells are
seeded on top of the material to evaluate its bioactivity. Under in vivo condi-
tions, an implant is placed within a tissue and thus tissues and less single cells
will contact the implant. It is generally accepted that cells in a 3D environment
behave differently from those in a 2D environment [
12
,
56
,
66
,
102
]. Nearly 25
years ago Sutherland started to use multicellular spheroids as an experimental
model to elucidate processes taking place in a tumour [
133
]. Since the multi-
cellular spheroids made of tumour cell line cells closely resemble solid tumours,
it has recently been suggested to use this model as a high-throughput test system
for antitumour drug development [
77
]. Similarly we have proposed the use of
cell reaggregates of primary cells to evaluate biomaterials [
95
,
96
]. For this, cell
reaggregates are prepared of a defined cell number of one of the key cell types of
the tissue that after implantation will contact the implant. The latter reaggregate,
which can be seen as a kind of organoid, is placed on the test material and
outgrowth is assessed. Cells in this situation have the choice to grow out on the
material or to stay within their own context. One driving force to grow out of the
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