Biomedical Engineering Reference
In-Depth Information
work has been carried out. Others deal with chemically cross-linked materials, for example
glutaraldehyde as a biocompatible cross-linker. Again, space does not allow us to include
these. Instead we will concentrate on a limited range of work using physical gels as
'
materials which allow, indeed encourage, in vitro cell growth to proceed
unhindered, and generally in three dimensions. The material itself has to allow initial cell
attachment and then transport appropriate biochemical factors and nutrients, eliminate any
waste products and ideally encourage successful development, most often in a speci
scaffolds
'-
c
geometric fashion
-
for example to encourage growth of body part substitutes such as
arti
cial bladders.
A typical study is that by Stevens and co-workers (Stevens et al.,
2004
), in which the
Ca
2+
plus Na
+
alginate system is employed as a scaffold for articular cartilage tissue. As
already mentioned, this forms a very rapid and essentially irreversible gel. In this study a
range of alginate types and concentrations was employed, and both pre-gel viscosity and
post-gel Young
s modulus were measured. Subsequent in vitro cell culture of chondrocytes
in the gel and on the gel surface yielded so-called
'
'
alginate/cell constructs
'
.Thesewere
composed of cartilage that contained appropriate cartilage-speci
c proteoglycans and
collagen. The authors suggested that such
could be either transplanted or
regenerated within the alginate matrix. In this way, partial or full-thickness defects in
articular cartilage could be treated. They also commented that, because of the speed of
gelation (in this case, <1 min), injectable delivery of the gel, a fairly minor medical
procedure, could be used to
'
explants
'
fill defects in the articular surface of a patient.
Another paper, with several authors in common (Stevens et al.,
2005
), used agarose,
but fabricated into a
. First, a silicone mould was made of a biochemical
well plate. This was peeled away and a silicone replica of this produced by moulding,
but this time of the original silicone construct. Finally, hot agarose solution was poured
onto the second replica
'
stamp
'
-
now a direct silicone copy of the well plate
-
and allowed to
cool, and the gel was then peeled away. This consisted of a series of
'
posts
'-
an inversion
of the original wells
which could be used as surfaces for subsequent cell growth. This
procedure seems indirect, but presumably it was too dif
-
cult to produce direct agarose
moulds of the cell plate without employing cytotoxic release agents.
The posts were then
with a suspension of human osteoblasts in a bone mineral
(hydroxyapatite) scaffold, and their growth studied as a function of treatment and time.
The authors argued that the technique has the advantage that it produces patterns of
osteoblasts with control over the geometry, size and spacing between patterns of cells.
They asserted that the procedure of stamping cells directly on tissue engineering scaf-
folds may have many future uses in controlling the spatial incursion on scaffolds,
promoting cell hierarchical organization and controlling cell
'
inked
'
cell interactions.
Finally, in the context of scaffold materials, Hyland et al.(
2011
) examined changes in
the bulk material properties of various concentrations of chitosan
-
alginate mixtures on
addition of the mucopolysaccharide chondroitin, and how this was altered by the order of
addition. They found that chondroitin increased the mechanical strength of chitosan
-
-
alginate networks, and the highest modulus was obtained from samples made with
chitosan and alginate modi
first by chondroitin and then later by Ca
2+
. Average
pore size was slightly larger in samples modi
ed
ed by Ca
2+
first and then chondroitin. In
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