Biomedical Engineering Reference
In-Depth Information
have also been the subject of several studies. However, it is difficult to find a general rule
concerning cell behavior for such films, as this depends both on the properties of the film
(thickness, hydration, mechanical properties) and cell type. For instance, PEM made from
highly hydrated polysaccharides from a combination of polysaccharides and polyamino-
acids often yield gel-like films. Some cells are known to adhere poorly to hydrated surfaces
and materials that are too soft (Discher et al. 2005). This was indeed observed for chondro-
sarcoma cells, chondrocytes, and osteoblast adhesion onto films such as PLL/HA (Richert
et al. 2004a; Richert et al. 2004b), CHI/HA (Croll et al. 2006; Schneider et al. 2007b), PLL/
ALG (Elbert et al. 1999), or PLL/PGA (Picart et al. 2005a). However, for certain cell types,
softness is preferred. For instance, neuronal cells were found to adhere to COL/HA films
(Wu et al. 2007). The outer layer chemistry has been found to be important in some cases
as COL ending films showed improved adhesion, but COL was not necessary for adhesion.
Cortical neurons and hippocampal neurons were sensitive to a different surface chemis-
try. Similarly, Tezcaner et al. (2006) showed that photoreceptor cells exhibit good viability
on PLL/HA and PLL/CSA films. Gong et al. (2007) also reported that cartilage-mimetic
PEM films made of COL and CSA have a beneficial effect on cell attachment, proliferation
and also on glycosaminoglycan secretion. (CHI/PGA) films promoted the attachment and
growth of C2C12 myoblast cells (Song et al. 2009).
So far, it appears that there is limited understanding of the detailed molecular mecha-
nisms of cell adhesion onto these biomimetic films. In particular, there is only a study
that aimed to characterize the types of integrins involved in cell adhesion, PSS/PAH films
being taken as substrate (Boura et al. 2005).
ECM Protein and Peptide Coatings on PEM Films
Several studies have tried to increase cell adhesion on PEM films by coating the final layer
with adhesion-promoting molecules such as fibronectin (FN), vitronectin (VN), or COL
that are known to engage specific cell receptors (Alberts et al. 1994). In this paragraph, we
discuss studies that deal with cell interactions onto the ECM protein modified films. The
first step of these studies is to characterize and quantify protein adsorption on the films.
The underlying idea is to give an additional functionality to the films by enhancing cell
interactions while preserving the “bulk” properties (biodegradability, mechanical proper-
ties, etc.). Wittmer et al. (2007) added a final fibronectin layer to PLL/DEXS films and found
that higher amounts of fibronectin were adsorbed on positively charged PLL ending films.
Human umbilical vein endothelial cells spread to a greater extent and more symmetrically
on FN-coated films. They also concluded that the presence of FN is a more important fac-
tor than film charge or layer number in controlling the interactions between multilayer
films and living cells. Kreke et al. (2005) quantified FN adsorption onto PAH/HEP films at
various pH solutions and found the highest FN adsorption at pH 8.4, which they attributed
to a charge effect. However, adsorbed amount of FN was not the sole factor explaining the
differences observed in cell adhesion strength. Semenov et al. (2009) showed recently that
FN adsorbed onto cross-linked PLL/HA films promoted focal adhesion formation and
was critical for maintaining densely grown mesenchymal stromal cell cultures over weeks
for their differentiation.
A similar study was conducted on PAH/PSS films by Li et al. (2005). After coating the
films with FN or GEL, they observed a general increase in the adhesion and proliferation
of SMCs. However, they also noted that these properties depend on the number of layers
in the PEM, meaning that not only outer layer chemistry but also film bulk nanostructure
control cellular adhesion.
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