2.1 Monomeric and Polymeric Precursors, Crosslinkers
Several monovinyl–divinyl comonomer pairs have been used for the preparation of
cryogels by free-radical crosslinking copolymerization. Mainly, water-soluble
monomers have been used in the synthesis of cryogels, such as acrylamide
(AAm) [16, 24–26], N,N-diethylacrylamide [27], N,N-dimethylacrylamide
(DMA) [28–30], acrylic acid (AAc) [31], N-isopropylacrylamide (NIPA) [32–34],
2-hydroxyethyl methacrylate (HEMA) [35], and 2-acrylamido-2-methylpropane
sulfonic acid sodium salt (AMPS) [36], in combination with N,N-methylene(bis)
acrylamide (BAAm), poly(ethylene glycol diacrylate), or biodegradable
crosslinkers [33, 35]. Nanosized clay particles (Laponite) can also be used as a
multifunctional crosslinker in the preparation of cryogels exhibiting very high
extensibility [34]. An ammonium persulfate (APS) and N,N,N
0 ,N
0 -
tetramethylethylenediamine (TEMED) redox initiator system is generally used to
initiate the polymerization reactions. Since the decomposition of the radical initiators is temperature dependent, the reaction solutions should be cooled before
addition of the initiator. Otherwise, gelation will start before freezing of the
reaction system, resulting in the formation of conventional gels. Alternatively,
polymerization inhibitors such as hydroquinone can be included in the reaction
system to shift the onset of the reactions beyond freezing of the solution
[23]. Cryogelation reactions can also be initiated by ultraviolet (UV) or electronbeam radiations so that the freezing time before the initiation step can be controlled
[37–39]. Controlled radical polymerization techniques such as reversible additionfragmentation chain transfer (RAFT) reactions have also been utilized for the
preparation of cryogels both in aqueous and organic media [30, 40]. Inspired by
the double-network (DN) technology developed by Gong and coworkers [6], DN
cryogels with dual sensitivity have also been prepared by conducting the
cryogelation reactions within the macropores of the single-network cryogels [41].
Cryogels can also be prepared starting from linear polymers in the presence of a
chemical crosslinker in aqueous or organic solutions. Several natural and synthetic
polymers have been used for the preparation of cryogels. The most popular
crosslinker for proteins is glutaraldehyde, which is highly active towards the
amine groups of a peptide chain in aqueous solutions. Proteins (e.g., gelatin,
fibrinogen, collagen, and bovine serum albumin), polysaccharides (e.g., chitosan,
hyaluronic acid), and synthetic polymers such as polyacrylamide (PAAm) and poly
(vinyl alcohol) (PVA) can be crosslinked using glutaraldehyde in their frozen
solutions [17, 42–44]. Cryogels were also prepared via crosslinking of amino
end-functionalized star-shaped poly(ethylene glycol) with heparin in aqueous solutions [45]. However, it is not always necessary to use a crosslinker in the preparation of cryogels from polymeric precursors. For example, the hydrogen bonds
formed between PVA chains in the unfrozen reaction phase lead to microcrystalline
domains that act as crosslinkers in PVA cryogels [44, 46].
Di-epoxides such as ethylene glycol diglycidyl ether (EGDE) and 1,4-butanediol
diglycidyl ether (BDDE) in the presence of TEMED catalyst have been used as
Synthesis and Structure–Property Relationships of Cryogels
109
Several monovinyl–divinyl comonomer pairs have been used for the preparation of
cryogels by free-radical crosslinking copolymerization. Mainly, water-soluble
monomers have been used in the synthesis of cryogels, such as acrylamide
(AAm) [16, 24–26], N,N-diethylacrylamide [27], N,N-dimethylacrylamide
(DMA) [28–30], acrylic acid (AAc) [31], N-isopropylacrylamide (NIPA) [32–34],
2-hydroxyethyl methacrylate (HEMA) [35], and 2-acrylamido-2-methylpropane
sulfonic acid sodium salt (AMPS) [36], in combination with N,N-methylene(bis)
acrylamide (BAAm), poly(ethylene glycol diacrylate), or biodegradable
crosslinkers [33, 35]. Nanosized clay particles (Laponite) can also be used as a
multifunctional crosslinker in the preparation of cryogels exhibiting very high
extensibility [34]. An ammonium persulfate (APS) and N,N,N
0 ,N
0 -
tetramethylethylenediamine (TEMED) redox initiator system is generally used to
initiate the polymerization reactions. Since the decomposition of the radical initiators is temperature dependent, the reaction solutions should be cooled before
addition of the initiator. Otherwise, gelation will start before freezing of the
reaction system, resulting in the formation of conventional gels. Alternatively,
polymerization inhibitors such as hydroquinone can be included in the reaction
system to shift the onset of the reactions beyond freezing of the solution
[23]. Cryogelation reactions can also be initiated by ultraviolet (UV) or electronbeam radiations so that the freezing time before the initiation step can be controlled
[37–39]. Controlled radical polymerization techniques such as reversible additionfragmentation chain transfer (RAFT) reactions have also been utilized for the
preparation of cryogels both in aqueous and organic media [30, 40]. Inspired by
the double-network (DN) technology developed by Gong and coworkers [6], DN
cryogels with dual sensitivity have also been prepared by conducting the
cryogelation reactions within the macropores of the single-network cryogels [41].
Cryogels can also be prepared starting from linear polymers in the presence of a
chemical crosslinker in aqueous or organic solutions. Several natural and synthetic
polymers have been used for the preparation of cryogels. The most popular
crosslinker for proteins is glutaraldehyde, which is highly active towards the
amine groups of a peptide chain in aqueous solutions. Proteins (e.g., gelatin,
fibrinogen, collagen, and bovine serum albumin), polysaccharides (e.g., chitosan,
hyaluronic acid), and synthetic polymers such as polyacrylamide (PAAm) and poly
(vinyl alcohol) (PVA) can be crosslinked using glutaraldehyde in their frozen
solutions [17, 42–44]. Cryogels were also prepared via crosslinking of amino
end-functionalized star-shaped poly(ethylene glycol) with heparin in aqueous solutions [45]. However, it is not always necessary to use a crosslinker in the preparation of cryogels from polymeric precursors. For example, the hydrogen bonds
formed between PVA chains in the unfrozen reaction phase lead to microcrystalline
domains that act as crosslinkers in PVA cryogels [44, 46].
Di-epoxides such as ethylene glycol diglycidyl ether (EGDE) and 1,4-butanediol
diglycidyl ether (BDDE) in the presence of TEMED catalyst have been used as
Synthesis and Structure–Property Relationships of Cryogels
109