Biomedical Engineering Reference
In-Depth Information
visible light is less-thermogenic yet causes less cell damage. In addition, visible
light penetrating through human skin provided greater depth of cure than UV [ 19 ].
Riboflavin (vitamin B2) [ 20 ], eosin-Y [ 21 , 22 ], or ruthenium (Ru (II))/sodium per-
sulphate (SPS) [ 23 ] have been used as a visible light initiator.
Crosslinking via reactions between functional groups present in the water-
soluble monomers or macromers produce hydrogels. Classical organic reactions
between functional groups such as the Michael addition, click reaction, Schiff
base formation, epoxide coupling, genipin coupling, and disulfide exchange
reaction have been used to prepare hydrogels. The Michael addition of nucleo-
philes (amine or thiol group) to ʱ , ʲ -unsaturated carbonyl compounds or ʱ , ʲ -
unsaturated sulfones in water forms hydrogels. Various functionalized polymers,
such as poly(ethylene glycol) (PEG) [ 24 - 26 ], poly(vinyl alcohol) (PVA) [ 27 ],
N-isopropylacrylamide (NIPAAm) [ 28 ], and natural polymers [ 14 , 29 ] have been
crosslinked via Michael addition and formed hydrogels. The copper [Cu(I)] cata-
lyzed azide-alkyne cycloaddition is one of the most popular click chemistry reac-
tions. Macromolecular derivatives of PVA [ 30 ], PEG [ 31 - 33 ], NIPAAm [ 34 ], and
polysaccharides [ 35 ] with Cu(I) as a catalyst have been used to prepare in situ
forming hydrogels. However, cytotoxic problem of Cu(I) should be solved to use
these click chemistry induced hydrogels for biomedical applications. Thus, Cu(I)-
free click reactions have been developed to be used as a tissue engineering scaf-
folds [ 36 , 37 ]. The Diels-Alder reaction, highly selective [4 + 2] cycloaddition
between a diene and a dienophile without a catalyst, is also known as a click type
reaction. Diels-Alder click crosslinked PEG [ 38 ], NIPAAm [ 39 ], or hyaluronic
acid (HA) [ 40 , 41 ] based hydrogels have been investigated for tissue engineering
applications.1
There has been an increased interest in the enzymatically crosslinked hydro-
gels that shows few side reactions since their high specificity for substrates.
Horseradish peroxidase (HRP)/hydrogen peroxide (H 2 O 2 ), transglutaminase (TG),
phosphatase (PP), tyrosinase, or thermolysin catalyzed crosslinking provides in
situ hydrogel formation of hydroxyphenyl propionic acid (HPA) functionalized
8-arm PEG [ 42 ], thiol functionalized poly(glycidol) [ 43 ], Tetronic-tyramine (Tet-
TA)/gelatin-HPA (GFPA) [ 44 ], dextran-tyramine (Dex-TA) [ 45 ], alginate-g-pyr-
role [ 46 ], or protein polymers containing either lysine or glutamine [ 47 ]. These
enzymatic crosslinks provide fast gelation.
3 Physical Hydrogels
Heat, ions, inclusion complex, stereocomplex, and/or complimentary binding can
induce a hydrogel formation by forming physical junctions via molecular entan-
glement, crystalline order, or intermolecular interactions. Hydrogels formed by
physical association are called physical, reversible, and stimuli responsive hydro-
gels. These hydrogel systems should be biocompatible with a host as well as the
incorporated bioactive agents.
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