Biomedical Engineering Reference
In-Depth Information
2 Hydrogels Crosslinked by Hydrogen Bonding
The most important supramolecular interaction in Nature is hydrogen bonding. In
biomolecules like dsRNA and DNA, two single strands are assembled by comple-
mentary base pairing, thymine-adenine, guanine-cytosine, and uracil-adenine, to
form helixes. Even though a single hydrogen bond is rather weak, with binding
energies of 10-65 kJ mol
−
1
[
77
], multiplicity of this interaction along with
ˀ
-
ˀ
stacking makes DNA double helixes stable against disintegration in water. The sta-
bility of DNA helixes is also increased by the ability of nucleobases to form sec-
ondary hydrogen bonds to one another [
16
,
34
].
A typical form of hydrogen-bonded hydrogels found in Nature is those based
on polysaccharides like cellulose [
78
-
80
], starch [
26
,
81
], and agarose [
82
,
60
].
In contrast to DNA, where hydrogen bonds link purine and pyrimidine bases, the
bonds in polysaccharide-based physical networks connect hydroxy groups of the
sugar units. In the case of cellulose, these interactions are so strong that with-
out any prior modification, cellulose is not water soluble at room temperature.
Thus, cellulose has been partly alkylated by etherification of the hydroxy groups
to increase its solubility in water [
83
,
79
]. The most abundant alkylated cellulose
derivatives are methyl, ethyl, hydroxyethyl, and hydroxypropylmethyl cellulose.
When solutions of these polymers are heated above certain temperatures, depend-
ing on the level of cellulose alkylation, hydrogels are obtained. The gelation mech-
anism involves hydrophobic interaction between the alkylated hydroxy groups:
at low temperature, cellulose chains are hydrated, whereas at high temperature,
water is repelled from the chains, and the alkylated hydroxy groups interact with
one another to form a hydrogel. This sol-gel transition can also be achieved by
addition of salts: the solvation of a salt is a competing reaction to polymer-water
hydrogen bonding, thereby removing water from the hydrated polymer chains and
entailing physical polymer crosslinking and hydrogel formation.
Alkylated derivatives of cellulose have applications throughout our daily lives,
such as those as thickening agents in food industry, emulsion stabilizers in sham-
poos, and humectants in pharmacy [
78
,
3
]. Inspired by these widespread applica-
tions, cellulose derivatives have also been tested for biomedical applications, but
hydrogels based solely on hydrogen bonding turned out to degrade too fast for these
areas of use. Therefore, blends of modified cellulose and polymers like synthetic
polyvinyl alcohol [
84
,
85
] or natural hyaluronic acid [
86
,
87
] have been investigated.
Shoichet and coworkers used a blend of methylcellulose (MC) and hyaluronic
acid (HA) to form hydrogels [
87
]. The aim of this effort was to design a hydrogel
that can be injected into the spinal cord. To achieve this goal, five criteria must be
met. First, the material has to gel suitably fast to prevent spreading of the hydro-
gel outside the target area. Second, injection of the hydrogel has to be minimally
invasively. Third, the material should not be cell adhesive, thereby preventing for-
mation of scar tissue due to decreased migration of fibroblasts into the gel [
88
].
Fourth, the hydrogel should be degradable to make further surgical interventions
obsolete. Fifth, the material has to be biocompatible to avoid immune reactions.
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