HYALURONAN-BASED HYDROGEL SCAFFOLDS - Intelligent Scaffolds for Tissue Engineering and Regenerative Medicine - page 166

have increased tremendously, and nowadays they are favored in
a wide range of implants, tissue engineering, pharmaceutical and
celltherapeutics,andotherbiomedicalapplications. 3 − 5 Bothnatural
and synthetic polymers have been employed for the fabrication of
hydrogels, such as HA, chondroitin sulfate, chitosan, fibrin, heparan
sulfate, alginate, dextran, poly(vinyl alcohol) (PVA), poly(ethylene
oxide) (PEO), Pluronic gel, and polyvinylidone, depending on their
purposes. These medical-grade polymers have been converted
to hydrogels via cross-linking methods. Numerous methods of
cross-linking of polymer chains for hydrogel formation have been
developed by various methods of either chemical or physical cross-
linkingsdepending on their target diseases and applications. 6 , 7
Amongtheabovemedicalgradepolymersforhydrogelnetworks,
HAhasbeenchosenasahighlyattractivenaturalpolymerforhydro-
gel fabrication, and numerous research groups have worked on the
development of synthesis methods of novel HA-based hydrogels so
as to take advantages of its excellent biological and chemical prop-
erties. Different synthesis methods, such as self-cross-linkings, pho-
topolymerization, and physical gelation, were developed according
to the needs of hydrogels specific for application purposes and tar-
get sitessuch as skins, bloodvessels, boneand cartilages.
Recently injectable, that is, in situ , HA hydrogels that turn into a
macroscopic gel at the local site of injection, 8 − 10 depending on sur-
rounding circumstances such as time, pH, enzymes, energy sources,
temperatures, and others, have drawn interest. Their advantages
in biomedical and pharmaceutical engineering applications include
convenient and safe delivery of bioactive molecules including stem
cells, patient comfort, minimal side effects, easy handling and cost
reduction. In situ HA hydrogelation has been achieved by vari-
ous methods, such as photopolymerization, normally irreversible
covalentbondseitherwithorwithoutcrosslinkermolecules,orself-
assembly by mechanisms of either reversible or irreversible chem-
ical reactions. Self-cross-linking hydrogels in response to a certain
external stimuli (e.g., temperature, pH, time lapse) and hydrogels
that release their contents in response to biological stimulus or its
degradation 11 , 12 havebeenrecognizedtobeofmostinterestamong
these gelling systems. In the following sections, various strategies
to create gelling methods are outlined, including introduction of