Biomedical Engineering Reference
In-Depth Information
of hydrogels formed in situ triggered by a variety of enzymes are
introduced.
6.2 In situ -Formed Hydrogels as Injectable Scaffolds
Since a hydrogel was first applied to soft lenses in the 1960s, a
large number of hydrogels have been exploited and investigated for
pharmaceutical and biomedical applications. Among these, hydro-
gels formed in situ are advantageous in avoiding invasive surgical
implantation,becauseapolymersolutionisinjectedandthenforms
ahydrogelwiththedesiredshapeinthebody.Inotherwords,asolu-
tion of the gel precursor mixed with cells can potentially be injected
through aneedle to fill a defect many times larger than the injection
needle itself.
To accomplish such an injectable function, the hydrogel should
be obtained using a particular cross-linking method enabling rapid
and nontoxic gelation under mild aqueous conditions. In situ cross-
linking methods for injectable hydrogels have been developed by
the self-assembly of molecules by stimuli (temperature, pH, ionic
strength, etc.), mild reactions, such as Michael and Schiff-base reac-
tions, or photo-cross-linking or photo-polymerization. 9 - 11 These
methods have accompanied a lack of function in practical uses, such
as hydrogel strength, solubility, solution viscosity, and toxicity. In
recent years, an attractive approach using an enzyme-catalyzed
reaction was suggested for the in situ formation of hydrogels. This
approach enables hydrogels not only to be formed under mild con-
ditionsforshortperiodsbutalsotobestrengthenedduetochemical
cross-linking, which are major issues in the development of hydro-
gels in situ .
In addition to an injectable function, a hydrogel as a matrix for
regenerative medicine requires more complicated functions as well
as physical and biological properties. These functions and prop-
erties include controlled biodegradation, insoluble signaling mole-
cules, soluble growth factors, and tissue-specific matrix stiffness,
which we will not deal with in this chapter because they have been
reviewed in manybooks.
 
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