Biomedical Engineering Reference
In-Depth Information
or oligomers, such that the resulting copolymers show an LCST behavior at
a certain critical composition of these reactants [105, 107]. The above phase
separation behavior of polymers that especially have an LCST temperature
close to the body temperature can be exploited to create tissue engineering
scaffolds. Here, the in situ gelation of the starting polymer solution could
be achieved by a subtle change in temperature [107]. Stile et al. used such
PNIPAm-based hydrogels for cartilage tissue engineering as an injectable
scaffold, which when gelled exhibited good chondrocyte cell viability [277].
In another study, peptide modified-PNIPAm hydrogels have been used to
encapsulate rat calvarial osteoblasts with good cell viability [278]. Thermore-
versible polypropylene fumerate-co-ethylene glycol hydrogels have also been
utilized for bone tissue engineering as discussed earlier [107].
The temperature-triggered gelation of PNIPAm has also been explored for
other biomedical applications such as drug delivery, and surface modifica-
tion of cell culture dishes in order to create thermoresponsive culture surfaces
upon which monolayers and multilayers of cells can be cultured and subse-
quently harvested noninvasively [279]. This technique known as “cell-sheet”
engineering has been applied to a number of different cell types such as en-
dothelial cells, kidney cells, and lung cells [280-283]. The latter application
arises due to fact that at body temperature (37
◦
C), PNIPAm is hydrophobic
and promotes cell adhesion, however at temperatures below 32
◦
CPNIPAm
becomes hydrophilic, loses its cell adhesion properties and consequently re-
leases the adhered cells. Therefore, one can easily lift off the cell sheets from
the surface since this technique still retains cell-cell contacts. Such cell-sheets
could be used to produce layered tissues by organizing the cell layers one on
top of each other [282, 283]. However, a close look at the swelling-collapse
phenomenon of PNIPAm shows that its hydration and dehydration kinetics
are slow, and which can adversely affect the spontaneous cell-sheet detach-
ment. In order to circumvent this limitation, Kwon et al. incorporated highly
hydrophilic PEG oligomers at the interface between the PNIPAm chains and
the cell layer [281].
Another approach to create a reversible biomimetic system is the creation
of antigen responsive hydrogels [114, 115]. Miyata et al. developed a hydro-
gel, which can swell reversibly in response to a specific antigen (rabbit IgG)
and change its structure. The hydrogel was prepared by grafting the anti-
gen (rabbit IgG) and the corresponding antibody (GAR IgG) to the polymer
network such that the binding between the antibody and antigen resulted in
a crosslinked network. The hydrogel swells in the presence of free antigens
because the physical crosslinks created by the antigen-antibody binding dis-
sociateviatheexchangeofgraftedantigenswiththefreeantigens.Similar
approaches can be used to create polymeric systems that could undergo in
situ gelation for tissue engineering.
In addition to the above discussed synthetic polymers, some natural
polymers such as gelatin, agarose, chitosan, etc, also undergo temperature-
