Coating of Material Surfaces with Layer-by- Layer Assembled Polyelectrolyte Films - Biological and Biomedical Coatings: Processing and Characterization - page 344

ProteinAdsorptionandCellAdhesionontoPEMFilms
Nonfouling Films
Non- or low-fouling surfaces are interesting in biomedical applications for two reasons.
They can be an effective way of controlling cellular and bacterial adhesion by enhanced
resistance to serum proteins. Rendering a surface nonfouling can also serve as immuno-
“camouflage” to prevent immune rejection of implanted biomaterials or to enhance the
efficiency of injected drug delivery vehicles. The proteins adsorbed on a material's surface
may in fact be denatured, or the material's surface itself may present epitopes that could be
recognized as foreign by the immune system and will thus induce immune reactions (Chen
and Scott 2001). Derivatives of polyethylene glycol (PEG), a highly hydrated polymer, are
very effective in rendering surfaces nonadsorbent to proteins and have been widely used
since the 1990s to modify various substrates (Wagner et al. 2004). Compared to the stan-
dard chemical grafting techniques used for PEG surface functionalization, multilayer film
depositing has the advantage of being rather independent of the nature or topology of the
material. Thus, PEM films have been constructed using PEG-grafted polymers (Boulmedais
et al. 2004) or by depositing a PEG layer on top of the films (Kidambi et al. 2008), yielding
a nonfouling multilayer film. In a more biomimetic approach, phosphorylcholine (PC) and
ethylene oxide (EO) 3 groups, which are naturally nonfouling components of erythrocyte
membranes, have been grafted onto a (PSS/PAH) film, thereby lowering protein adsoption
(Reisch et al. 2009). The nonfouling properties were attributed to the zwiterionic proper-
ties of the molecules. Films containing natural polysaccharides are often nonfouling and
nonadhesive for cells because of their high water content and softness.
One of the advantages of nonfouling PEM is their ability to create a so-called “blank
slate” (Croll et al. 2006) (e.g., a nonadhesive surface that can be subsequently modified
by covalently grafting adhesion peptides). Croll et al. (2006) presented cytophobic PEM
made from high-molecular-weight hyaluronanic acid and chitosan that was resistant to
serum protein adsorption. Upon covalent grafting of collagen IV on top of the films, the
films switched to cytophilic. A similar strategy based on “click” chemistry was recently
proposed by Kinnane et al. (2009). Alkyne or azide groups incorporated into the polymer
are used to create covalent linkages between polymer layers or between polymers and
other molecules under mild conditions (Kinnane et al. 2009). In this study, they designed
low fouling PEG acrylate multilayers onto which they “clicked” an RGD peptide. Monkey
kidney epithelial cells adhered and grew only on the RGD-functionalized PEG films.
Films Made of Synthetic Polyelectrolytes as Cell Adhesive Substrates
Synthetic polyelectrolytes such as PSS (a strong polyelectrolyte), PAA, or PAH have been
widely used in cell/film studies. In this case, initial cell adhesion is mostly mediated
through electrostatic interaction and, more indirectly, via serum proteins adsorbed onto
the films. The main advantages of using synthetic polymers are: (1) the possibility of spe-
cifically adjusting certain parameters and (2) the possibility to easily chemically modify
them.
The most frequently studied synthetic PEM is, by far, linearly growing and dense PSS/
PAH films. Cell types such as endothelial cells (Boura et al. 2003), fibroblasts (Brunot et
al. 2008; Mhamdi et al. 2006), osteoblastic cells (Tryoen-Toth et al. 2002), and hepatocytes
(Wittmer et al. 2008) have been cultured on these films. As a general rule, adhesion and