(mentioned in Sect. 2.1) as well as those based on starch-polysaccharides [268, 269]
are also noncovalent cryogels that are stable at room temperature, but can be fused
upon heating to 70–90
C.
There is also a special case of the formation of physical cryogels where the selfgelation processes occur at a high rate even at positive temperatures. The aqueous
solutions of >1 wt% agarose or >5–10 wt% gelatine belong to this category of
gel-forming systems. When such solutions are being frozen at a moderate negative
temperature, the ice is formed inside the already formed polymeric gel rather than
in the liquid feed solution. As a consequence, the cryo-concentrating processes will
not be realized to a significant extent, and the growing solvent polycrystals can even
destroy the primary gel structure. The preparation of cryogels based on such
quickly self-gelling precursors requires that freezing of the initial polymer solution
should occur before the onset of the gelation. Principally, there are two possible
ways to achieve this goal (1) freezing the initial hot solution very rapidly, e.g., in a
liquid nitrogen bath, or (2) decreasing the self-gelation rate of the precursors by
using specific additives capable of partially inhibiting the sol-to-gel transition.
These two options were examined in detail in gelation systems containing agarose
as a polymeric precursor [270, 271]. It was shown that the first option results in
rather brittle gel materials with micrometer-sized pores. For the second approach,
that is, to reduce the self-gelation rate of the precursor system, some solutes capable
of partially interfering with H-bond formation between agarose chains were introduced into the initial feed solutions. This resulted in agarose cryogels with porosity
and operational properties suitable for various applications, e.g., as wide-pore
scaffolds for culturing of animal or human cells, including stem cells [271–277],
and as supermacroporous continuous chromatographic beds for manipulation of
particulate sorbates like viruses, cell organelles, and whole cells [272, 278]. It was
found that the most convenient method of decelerating self-gelation in agarose
solutions is to shift the pH so that some of the agarose hydroxyl groups are ionized,
thus creating charges of the same sign along the chains, which causes certain
repulsion between the chains [271].
Examples of various physical cryogels are summarized in Table 3, where the
data are categorized according to the nature of the polymeric precursors, namely,
polysaccharides, proteins, and synthetic polymers. The data for PVA cryogels are
given separately due to the large number of papers published on these cryogels.
The history of PVA cryogels is also interesting because such gel systems have
been discovered twice, as it were. First, there were mainly empiric recordings on the
formation of these cryogels [230, 231] and the first patents were issued on the
“virtual” applied possibilities of such materials [226–229]. Almost 10 years later,
two approaches for increasing the strength of PVA cryogels were reported, namely,
multiple freeze–thaw processing [299, 365–370] and the partial dehydration of
frozen specimens in vacuo [9, 300, 301, 371]. These findings initiated numerous
fundamental studies due to the amazing combination of cryogel properties and their
macroporous structure. The investigations of frozen PVA solutions by nuclear
magnetic resonance (NMR) and electron spin resonance (ESR) allowed better
understanding of the fine details of the gelation processes inside frost-bound
A Brief History of Polymeric Cryogels
23
are also noncovalent cryogels that are stable at room temperature, but can be fused
upon heating to 70–90
C.
There is also a special case of the formation of physical cryogels where the selfgelation processes occur at a high rate even at positive temperatures. The aqueous
solutions of >1 wt% agarose or >5–10 wt% gelatine belong to this category of
gel-forming systems. When such solutions are being frozen at a moderate negative
temperature, the ice is formed inside the already formed polymeric gel rather than
in the liquid feed solution. As a consequence, the cryo-concentrating processes will
not be realized to a significant extent, and the growing solvent polycrystals can even
destroy the primary gel structure. The preparation of cryogels based on such
quickly self-gelling precursors requires that freezing of the initial polymer solution
should occur before the onset of the gelation. Principally, there are two possible
ways to achieve this goal (1) freezing the initial hot solution very rapidly, e.g., in a
liquid nitrogen bath, or (2) decreasing the self-gelation rate of the precursors by
using specific additives capable of partially inhibiting the sol-to-gel transition.
These two options were examined in detail in gelation systems containing agarose
as a polymeric precursor [270, 271]. It was shown that the first option results in
rather brittle gel materials with micrometer-sized pores. For the second approach,
that is, to reduce the self-gelation rate of the precursor system, some solutes capable
of partially interfering with H-bond formation between agarose chains were introduced into the initial feed solutions. This resulted in agarose cryogels with porosity
and operational properties suitable for various applications, e.g., as wide-pore
scaffolds for culturing of animal or human cells, including stem cells [271–277],
and as supermacroporous continuous chromatographic beds for manipulation of
particulate sorbates like viruses, cell organelles, and whole cells [272, 278]. It was
found that the most convenient method of decelerating self-gelation in agarose
solutions is to shift the pH so that some of the agarose hydroxyl groups are ionized,
thus creating charges of the same sign along the chains, which causes certain
repulsion between the chains [271].
Examples of various physical cryogels are summarized in Table 3, where the
data are categorized according to the nature of the polymeric precursors, namely,
polysaccharides, proteins, and synthetic polymers. The data for PVA cryogels are
given separately due to the large number of papers published on these cryogels.
The history of PVA cryogels is also interesting because such gel systems have
been discovered twice, as it were. First, there were mainly empiric recordings on the
formation of these cryogels [230, 231] and the first patents were issued on the
“virtual” applied possibilities of such materials [226–229]. Almost 10 years later,
two approaches for increasing the strength of PVA cryogels were reported, namely,
multiple freeze–thaw processing [299, 365–370] and the partial dehydration of
frozen specimens in vacuo [9, 300, 301, 371]. These findings initiated numerous
fundamental studies due to the amazing combination of cryogel properties and their
macroporous structure. The investigations of frozen PVA solutions by nuclear
magnetic resonance (NMR) and electron spin resonance (ESR) allowed better
understanding of the fine details of the gelation processes inside frost-bound
A Brief History of Polymeric Cryogels
23