Biomedical Engineering Reference
In-Depth Information
and a pH of 7.2, which gels at 37°C, while slight acidification to pH 6.85 increases the
gelation temperature to nearly 50°.
As mentioned in Section 1.2.2, chitosan-g-PEG prepared by Bhattarai et al. was soluble
at physiological pH and exhibited injectable property, due to the graft of PEG chains. The
sol-gel transition on increasing the temperature of the copolymer above 25°C was con-
trolled by the degree of substitution of PEG on the chitosan chain, PEG molecular weight,
and concentrations of the polymers [37,38]. While not fully understood, gelation mecha-
nism involving hydrophobic interactions, hydrogen bonding, and hydrophobic associa-
tions were supposed to be the main driving force. It was believed that at low temperatures
the H-bonding between PEG and water molecules dominates, while at high temperatures
the hydrophobic interactions between polymer chains prevail [4,37,56]. The hydrophilic-
hydrophobic transition results in gel formation [4].
Other examples of chitosan-based copolymers are chitosan-g-NIPAAm and chitosan-g-
Pluronic [35,41]. PNIPAAm and Pluronic are themselves thermosensitive synthetic poly-
mers that can form gels at elevated temperature. Their structures share the common
characteristic of having both hydrophilic and hydrophobic domains. When grafted onto
chitosan molecules, they convert chitosan into physically cross-linked hydrogel. The
increase in strength of the hydrophobic interactions of hydrophobic groups with increas-
ing temperature enhances the interactions between adjacent chitosan chains, leading to
the formation of hydrogel. The gelation temperature primarily depends on the content
ratio of chitosan and the grafted chains [57], that is, the balance between hydrophilic and
hydrophobic interactions. Take chitosan-g-Pluronic for example: the gelation temperature
was controlled by chitosan content, and gelation did not occur when the chitosan content
was >17 wt% [35,57].
6.3.1.3 Hydrogen Bonding
By blending with some water-soluble nonionic polymers, chitosan can form hydrogels
through other secondary bonding, that is, H-bonding [58-61]. This is because chitosan pos-
sesses many hydroxyl and amino groups along its molecular chain, which provides chances
for chitosan to cross-link with other macromolecules having hydroxyl and amino groups
(i.e., PVA and cellulose) through H-bonding [58-61]. PVA is the most commonly used poly-
mer of this kind, since a number of -OH groups exist on the chain. The mixing of chitosan
and PVA forms junction points in the form of interpolymer complexation or crystallites
after a series of freezing/thawing cycles. The chain-chain interactions act as cross-linking
sites of the hydrogel. In the case of chitosan-PVA polymer blends, increasing the chitosan
content negatively affects the formation of PVA crystallites, leading to the formation of
hydrogels with less ordered structures [4]. PVA was also grafted onto chitosan to form chi-
tosan-g-PVA, avoiding the phase separation during mixing of component materials [59].
This polymer can form physically cross-linked hydrogel through the same mechanism.
6.3.2 Chemical Cross-linked Hydrogel
Several chemical ways were explored to build covalent bonds to cross-link chitosan,
leading to the formation of hydrogel. The mechanism of the formation of these hydro-
gels mainly includes Schiff base formation, Michael addition, enzyme (horseradish per-
oxidase—HRP)-catalyzed reaction, polymerization, and so on. Some small-molecule
cross-linkers and/or functional groups conjugated to polymers are often involved in the
procedure.
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