Biomedical Engineering Reference
In-Depth Information
circulating blood, begins with the unspecific adsorption of plasma proteins (Andrade &
Hlady, 1986; Harris, 1992; Horbett, 1993).
Not only with regards to tissue engineering and implant design unspecific protein
adsorption is a highly critical process, also different devices in diagnostics (e.g. protein
arrays) and biosensors are based on specific receptor-ligand binding, demanding a non-
interacting background. Therefore, much effort has been focused on the development of
inert, protein resistant materials and coatings (Chapman et al., 2000; Elbert & Hubbell, 1996).
Many synthetic hydrophilic polymers, including PAA, PHEMA, PVA, PEG and
poly(ethylene oxide) (PEO) have been applied for this purpose (see Figure 1) (Castillo et al.,
1985).
1.2 Biomedical applications of PEG- or PEO-based hydrogels
Some of the earliest work on the use of PEG and PEO as hydrophilic biomaterials showed
that PEO adsorption onto glass surfaces prevented protein adsorption (Merrill et al., 1982).
Several subsequent studies confirmed that PEO, or its low molecular weight (Mw<10 kDa)
equivalent, PEG, were showing the most effective protein-repellent properties (Harris,
1992). PEG-modified surfaces are non-permissive to protein adsorption, bacterial adhesion
and eukaryotic cell adhesion (Zhang et al., 1998; Desai et al., 1992; Drumheller et al., 1995;
Krsko et al., 2009.
Based on these properties, PEG hydrogels are one of the most widely studied and used
materials for a variety of biomedical applications such as tissue engineering, coating of
implants, biosensors, and drug delivery systems (Langer & Peppas, 2003; Langer & Tirell,
2004; Krsko & Libera, 2005; Tessmar & Gopferich, 2007; Veronese & Mero, 2008; Harris &
Zalipsky, 1997). PEG substrates have also been used to generate patterns of proteins or cells
using for example the technique of microcontact printing (Whitesides et al., 2001; Mrksich &
Whitesides, 1996; Mrksich et al., 1997). PEG hydrogels are approved by the US Food and
Drug Administration (FDA) for oral and topical application; they are little immunogenic
and non-toxic at molecular weights above 400 Da. Since PEG itself is not degradable by
simple hydrolysis and undergoes only limited metabolism in the body, the whole polymer
chains are eliminated through the kidneys or eventually through the liver (Mw < 30 kDa)
(Harris, 1992; Knauf et al., 1988).
Many groups have investigated surface coverings of PEG or PEO in order to try to elucidate
why PEG has such remarkably effective properties and different theories have been
proposed (Jeon et al., 1991; Prime & Whitesides, 1993). First, there are generally only weak
attractive interactions between the PEG-coatings and a wide range of proteins, as protein
adsorption is generally known to be more pronounced on hydrophobic surfaces in
comparison to hydrophilic ones (Morra, 2000). Furthermore, as the interaction between
water and PEG via hydrogen bonds is more favorable and surpasses possible attractive
interactions of proteins with the surfaces, a repulsion force is created. Therefore the
hydration of the layer, i.e. the binding of interfacial water is of high relevance for the
exclusion of other molecules coming near the polymer surface (Harris, 1992; Harder et al.,
1998). Additionally, molecules approaching the rather flexible, loosely crosslinked PEG
hydrogel from the surrounding medium initiate the compression of the extended PEG
molecules inducing a steric repulsion effect (Jeon et al., 1991; Morra, 2000). More specifically,
a loosely crosslinked gel has relatively long segments between the crosslinks, which can take
a relatively large number of conformations. The number of segment conformations would
be substantially restricted by the binding of a protein molecule to the gel surface. This
