Biomedical Engineering Reference
In-Depth Information
[4-6]. Similar to classic vulcanization used to crosslink natural rubber, the
crosslinks may occur at any site along the backbone of the original polymer
chains. Although ionizing radiation is not ideal for the production of
protein/peptide hydrogels, radiation crosslinked PEG hydrogels have been
post-functionalized with monosaccharides to promote cell adhesion [6].
2.1.
Physical crosslinking
Physical crosslinking may be via multiple non-covalent interactions, for example
between heparin and a heparin-binding peptide end-attached to multiarm-PEG
[7, 8]. Crosslinks may also be formed between coiled coil-forming proteins
and PHMPA copolymers via histidine tags [9]. Further examples of hydrogels
formed by interactions of peptides have been recently reviewed [10]. Other
biological molecules may be used to physically crosslink PEG. Hybridization
between complementary DNA strands may also be used to form hydrogels [11].
The threading interaction between the PEG backbone and the cyclic
oligosaccharide cyclodextrin produces hydrogels simply by mixing unmodified
star PEG with cyclodextrins [12]. In cases where stoichiometric physical
interactions occur, multi-arm PEG may be needed for gel formation, while less
specific interactions may allow aggregation between multiple chains such that
linear PEG is sufficient for gel formation. Most hybrid self-assembled hydrogels
will be of the former type. While physical gelation has many attractive properties
such as rapid yet readily reversible
in situ
gelation, stable chemical crosslinks are
much more commonly utilized to produce hybrid materials.
2.2.
Chemical crosslinking of PEG — commonly used reactions
Chemical crosslinking by free-radical polymerization of PEG modified with
unsaturated groups may be initiated by thermal or photolytic degradation of an
initiator [13]. Chemical groups subject to free-radical polymerization are
typically reacted with the hydroxyl groups present at both termini of the linear
PEG chain. Each group that is subject to free-radical polymerization has a
functionality of two, meaning that each unsaturated group may propagate
polymerization of a linear polymer. Linear PEG chains have two hydroxyl
termini such that each modified PEG has a total functionality of four. Any
molecule with a functionality greater than two may serve as a crosslink site.
Thus, PEG molecules with more than one unsaturated group may be used to
form crosslinked materials. The most commonly utilized unsaturated groups
are acrylates, methacrylates and fumarates [3]. Hydrogels formed with
macromonomers such as PEG-diacrylate (PEG-DA) are structurally similar to
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