Biomedical Engineering Reference
In-Depth Information
to adsorb VEGF and for its biocompatibility toward endothelial cells. The authors demon-
strated that the VEGF adsorbed on (PAH/PSS)
4
maintained its bioactivity in vitro and
stimulated endothelial cells proliferation. A specific activation of the intracellular pathway
(VEGF receptor and MAP ERK1/2 kinase) was also evidenced.
Cell and Stem Cell Differentiation
Cells with capacities to differentiate, and stem cells in particular, are currently the subject
of several studies thanks to their potential applications in tissue repair in situ and tissue
engineering. Stem cells in vitro or in vivo are in “niches,” a term that refers to the stem cell
microenvironment (Scadden 2006). These niches are found during embryonic development
(embryonic stem cells) but also in the human body (adult stem cells), where the stem cells
can be activated by several signals to either promote self-renewal or differentiation to form
new tissues. Important characteristics within the niche are cell-cell interactions between
stem cells, as well as interactions between stem cells and neighboring differentiated cells,
interactions between stem cells and adhesion molecules, extracellular matrix components,
growth factors, cytokines, and physiochemical nature of the environment.
Scientists are studying the various components of the niche and trying to replicate the in
vivo niche conditions in vitro. This is because for regenerative therapies, cell proliferation
and differentiation must be controlled in flasks, so that a sufficient quantity of the proper
cell type is produced before being introduced back into the patient for therapy. Other cells,
such as skeletal muscle cells are called pluripotent in that they can differentiate in to dif-
ferent cell types depending on the signals received (Darabi and Perlingeiro 2008).
Studies concerning stem cell adhesion, proliferation, and differentiation on PEM films
are just emerging. Given the possibilities for spatially controlling film topography, provid-
ing cell cocultures, loading films with chemical factors such as morphogens and modulat-
ing film mechanical properties, PEM films appear to have great potential for applications
in stem cell-based tissue engineering.
Dierich et al. (2007) were the first to show the use of PEM films for the differentiation of
embryonic bodies (EBs) into cartilage and bone. A poly(l-lysine succinylated)/PGA film,
into which BMP2 and TGF
β
1 had been embedded, was chosen for this purpose. They
found that both BMP2 and TGF
β
1 needed to be present simultaneously in the film to trig-
ger proteoglycan production and drive the EBs to cartilage and bone formation. This con-
stituted the first example of a multilayer whose biological activity was based on a synergy
effect between two active compounds.
The same authors subsequently investigated the effect of a growth factor, BMP4, and
its antagonist, Noggin, embedded in a PLL/PGA film on tooth development (Nadiri et al.
2007). They showed that these films can induce or inhibit cell death in tooth development
and that the biological effects of the active molecules are conserved. The functionalized
PEMs could thus act as efficient delivery tools for activating cells. This approach shows
promise because it can be used to finely reproduce architectures with cell inclusions as
well as to provide tissue organization.
A recent study by Crouzier et al. (2009) gave the proof that controlled amounts of a mor-
phogen such as BMP2 can be trapped in a thick film made of (PLL/HA) and retain their
activity. The amount of BMP2 trapped could be adjusted by varying both the number of
layers in the film and the initial BMP2 concentration in solution. Interestingly, myoblast
cells grown on unloaded films differentiated into myotubes in a manner that depended on
the stiffness of the PLL/HA film (Ren et al. 2008). The same cells grown on BMP2-loaded
films differentiated into osteoblasts, the expression of alkaline phosphatase (a marker for
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