Biomedical Engineering Reference
In-Depth Information
Photogelation is also a viable technique for controlling the spatial organi-
zation of different cell types within a three-dimensional system [24, 272]. This
is accomplished by creating multilayer hydrogels where each layer is poly-
merized sequentially as shown in the schematic (Fig. 7). Integration between
the layers is maintained while keeping cells confined within their respective
layers. In our laboratory, such an approach has been used to encapsulate cells
from different layers of the native cartilage within different hydrogel strips to
create a stratified tissue engineered cartilage with zonal organization akin to
the native one [24]. Additionally, multilayer hydrogels also enable the creation
of other musculoskeletal tissues such as a whole knee joint with integrated
cartilage and bone tissue [272].
6.2
Smart Hydrogels
Smart hydrogels, also known as stimuli-responsive hydrogels, are polymer
networks that can undergo a discontinuous and macroscopic phase transi-
tionbetweenaliquidandasolidstatewhensubjectedtoasmallchangein
one or more environmental stimuli such as temperature [105, 273], pH [105],
light [274], radiation forces [275], and chemical triggers [115, 126-128, 276].
In the case of thermally reversible hydrogels, a subtle rise in the temperature
near the lower critical solution temperature (LCST) can be used to trigger the
sol-gel transition, where water-soluble coil structures transform into water-
insoluble globular structures in aqueous medium, and vice versa. The LCST
temperature is the manifestation of a critical balance of hydrophilic and hy-
drophobic groups, and significant research has been performed to tune the
LCST temperature [105, 121].
One of the most extensively investigated stimuli responsive polymers is
poly( N -isopropyl acrylamide), or in short, PNIPAm. PNIPAm exhibits a LCST
temperature around 32 C, which means PNIPAm hydrogels undergo a re-
versible swelling-collapse volume phase transition at 32 C [105]. During
this volume phase transition, the hydrogel expels the imbibed water. How-
ever, the phenomenon is reversible and the collapsed gel re-swells in water
as the temperature is decreased below its LCST (i.e. 32 C). The re-swelling
of the collapsed PNIPAm hydrogel as temperature decreases is accompa-
nied by hysteresis, i.e. the threshold temperature at which the swollen phase
transforms into a collapsed phase is different from the threshold tempera-
ture at which the reverse transition occurs. The transition temperature of
thermoreversible polymers can be manipulated by altering the hydrophilic-
hydrophobic balance [94]. For instance, copolymerizing PNIPAm with a hy-
drophobic monomer decreases its LCST temperature, whereas copolymeriz-
ing it with a hydrophilic monomer raises its LCST temperature [94].
In addition to PNIPAm, other synthetic thermoresponsive materials have
been developed by copolymerizing hydrophilic and hydrophobic monomers
 
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