Designing Hydrogels by ATRP - In-Situ Gelling Polymers: For Biomedical Applications - page 83

to concerns on potential cytotoxicity of poly(N-substituted acrylamide)s, poly-
methacrylates with pendant oligo(ethylene oxide) units, i.e. POEOMA, present
a promising alternative for the preparation of thermoresponive materials [ 162 ].
POEOMA-based polymers exhibit tunable LCST between 20 and 90 °C simply
by varying the composition of the POEOMA with different numbers of EO units
in the side chains [ 163 ]. One desirable characteristic for the development of ther-
moresponsive hydrogels is the ability to rapidly respond to changes in temperature
thereby providing fast deswelling or volume change.
One limiting factor for generation of rapid thermoresponsiveness is the forma-
tion of an impenetrable hydrophobic “skin layer” on the surface of the material;
this skin layer delays the release of water from the core of the hydrogel, which
contributes to a slow LCST transition from hydrophilicity to hydrophobicity of
thermoresponsive polymers [ 164 - 168 ]. Rapid response is achieved by allowing
fast water release from the gel matrix, and preventing formation of skin layers on
the surface of hydrogels caused by LCST transition of the thermoresponsive poly-
mers. The use of ATRP techniques for the preparation of hydrogels has resulted
in the preparation of materials that demonstrated rapid deswelling kinetics with
higher swelling ratio at a temperature above LCST of the hydrogels, compared to
counterparts prepared by conventional RP [ 169 ]. The rapid thermoresponsiveness
of ATRP gels is attributed to the formation of homogenous and uniform networks.
In contrast, FRP leads to non-uniform crosslinking [ 170 ]. Taking advantage of
this, several approaches utilizing ATRP have been explored to enhance the release
rate of water from thermoresponsive hydrogels (Fig. 5 ). A grafting strategy, uti-
lizing incorporation of dangling polymeric chains from the thermoresponsive
network of crosslinked hydrogels, was reported. The resulting hydrogels exhibit
thermoresponsive properties which can be customized by changing grafting den-
sity, grafting chain length, and chain composition [ 171 ].
Strategies utilizing disulfide-thiol degradation chemistry have also been explored.
Star-shaped macromolecular pore precursors, with degradable disulfide crosslinked
cores and hydrophilic poly(ethylene oxide) (PEO) arms, were incorporated into the
gel network. The cleavage of disulfide linkages generated thermoresponsive porous
hydrogels with efficient water-release channels, suppressing skin layer formation,
thus facilitating the release of water molecules [ 171 ]. Evaluation of these hydrogels
from a biomedical perspective takes advantage of the fact that the porous thermore-
sponsive hydrogels are non-cytotoxic and exhibit enhanced release of encapsulated
model drugs, suggesting potential application as effective tissue scaffolds.
Two approaches utilizing polymerizable POEOMA-based nanogels as multi-
functional crosslinkers have been reported for the development of nanostructured
hybrid hydrogels. The polymerizable crosslinked nanogels were prepared by post-
polymerization modification of carboxylic acid (COOH)-functionalized nanogels
with methacrylate groups. The methacrylate-functionalized nanogels were used as
multi-functional crosslinkers for a photo-induced FRP of dimethacrylates [ 172 ] or
thiol-ene polyaddition with hyaluronic acids having pendant thiols [ 173 ] yielding
hydrogels covalently embedded with nanogels domains.