Biomedical Engineering Reference
In-Depth Information
would lead to a relatively large unfavorable entropic change, making the process of protein
adsorption very unfavorable for thermodynamic reasons. Additionally, the high mobility of
PEG chains allows little time for proteins to form durable attachments.
Many techniques have been developed to create PEG or PEO-bearing surfaces, e.g. exploiting
physical adsorption, chemical coupling, and graft polymerization (Harris, 1992; Harris &
Zalipsky, 1997; Prime & Whitesides, 1993; Fujimoto et al., 1993; Prime & Whitesides, 1991).
Whitesides and co-workers have studied covalent coatings of oligo(ethylene glycol)s, so-called
self-assembled monolayers (SAMs) and found that the resistance to protein adsorption
increased with the chain length of the oligomers (Prime & Whitesides, 1991 and 1993).
Furthermore, it has been demonstrated that the adhesion resistance of PEG increases with
chain packing density (Sofia et al., 1998; Malmsten et al., 1998).
In recent years the versatility of star-shaped PEG molecules has been recognized, as they
present a high number of end-groups per molecule allowing interconnectivity and
functionalization (Groll et al., 2005a & 2005b; Lutolf et al., 2003). Some star polymers have
been shown to achieve a high surface coverage and localization of the end-groups near the
top of the star polymer (Irvine et al., 1996). Therefore, star-shaped PEG molecules are an
interesting and promising alternative to linear PEG.
1.3 PEG-based hydrogels formed by UV-curing: patternable biomaterials
We have been using PEG hydrogels that are prepared by UV-based radical crosslinking of
six-armed star-shaped macromonomers via acrylate (Acr) end-groups. The polymer
backbone consists of a statistical copolymer of 85 % ethylene oxide and 15 % propylene
oxide (P(EO-stat-PO)) and each star molecule bears 6 reactive Acr end-groups. The formal
notation of the precursor polymer would thus be Acr sP(EO stat PO). Nevertheless, in the
following the resulting, crosslinked network will be denoted PEG-based (hydro)gel, even
though the arms of the precursors do not consist of pure PEG, but contain a fraction (15%) of
propylene glycol units in the copolymer. These PO-units give the prepolymer its unique and
very useful property of being a liquid at room temperature, before crosslinking. The
crosslinking reaction was initiated by a UV-based radical reaction with benzoin methyl ether
as photoinitiator (PI) and an additional crosslinker (CL) (pentaerythritol triacrylate). Further
experimental details concerning the synthesis and the curing conditions can be found in our
recent publications (Lensen et al., 2007; Diez et al., 2009).
The hydrogel substrates were applied as free-standing bulk gels for 2D cell culture studies.
Due to the fact that the prepolymer Acr-sP(EO-stat-PO) is liquid before crosslinking, the
precursor mixture can be molded in any shape, which has enabled us to imprint desired
micro- and nanometer topographic patterns into the hydrogel surface (Lensen et al., 2007;
Diez et al., 2009). In the following, the properties of this hydrogel system in view of its use in
biomedical applications will be evaluated, e.g. the cytotoxicity and cytocompatibility will be
assessed, and the cell behavior on the surface of the hydrogels will be demonstrated. Finally,
the remarkable effect of surface topography and substrate elasticity on protein adsorption,
cell adhesion and cell spreading will be discussed.
2. Fabrication and properties of PEG-based substrates
2.1 Synthesis of PEG-based hydrogels from Acr-sP(EO-stat-PO) macromonomers
Hydrogels fabricated for the application in cell culture studies were crosslinked from Acr-
sP(EO-stat-PO) prepolymers. UV-irradiation was used to initiate radical polymerization of the
macromonomer mixture with added photoinitiator (PI) and crosslinking agent (CL) (
Figure 2
).
