Environment–Stimuli Response of Chitosan-Based Hydrogels - Chitosan Based Hydrogels: Functions and Applications - page 233

be adjusted by the components and the connection mode of each component. In general,
two cross-linking methods have been developed for preparing chitosan-based hydrogels:
physical or chemical cross-linking.

5.2.1 Physical Cross-linking of Chitosan-based Hydrogels

5.2.1.1 Chitosan-Derivative-Based Hydrogels

It is a very effective method to obtain pH-sensitive hydrogels via grafting some special
chemical function group or polymer on chitosan chains. Poly(α-hydroxy acids) can gener-
ate acidic degradation products at the implanted site, which evokes an undesirable tissue
reaction [5]. The acid by-product may lead to local disturbance due to poor vascularization
in the surrounding tissue. Chitosan may be combined with acid-producing biodegradable
polymers, so that local toxicity due to the acid by-products can be alleviated. Physically
cross-linked chitosan-g-poly(α-hydroxy acids) hydrogels have been carried out by direct
grafting of α-hydroxy acids onto chitosan in the absence of catalysts. The structure of the
graft copolymers can change according to the pH value of the environment because there
are unreacted amino groups of chitosan in chitosan-g-poly(α-hydroxy acids) acid copoly-
mers, which would be protonated in acid solutions. In the acidic condition, the acid can be
attached to the hydrogels, as shown in Figure 5.2. The swelling process of hydrogels con-
tains the protonation of amino groups by the acid in the low pH value (pH < p K b ) by the
ionic bonds; therefore, the chitosan-g-poly(α-hydroxy acids) hydrogels are able to imbibe a
lot of water and swell quickly. However, the swelling ability of the hydrogels becomes
unchanged when the pH value is higher than p K b [6]. Moreover, the pH-sensitive behav-
iors could be modulated via adjusting the side groups and degree of substitution. However,
the side groups and degree of substitution have less effect on sample swelling above p K b .
For example, Albertsson and coworkers [7] found that chitosan-g-poly(lactic acid) hydro-
gels appear to have higher water uptake values than chitosan-g-poly(glycolic acid) hydro-
gels at pH 2.2, but they have similar water uptake at pH 7.4. Yao et al. [8,9] obtained the
cytocompatible poly(chitosan-g-l-lactic acid) through grafting oligo(l-lactic acid) onto the
amino groups on chitosan without a catalyst. These graft copolymers have a higher
strength than chitosan and the swelling behaviors are influenced by pH (as shown in
Figure 5.3). When pH < 2, with increasing buffer pH, the concentration of charged ionic
groups in the films increases. The swelling of the samples will increase due to enhance-
ment of the osmotic pressure and charge repulsion. At higher pH, the degree of ionization
is reduced due to deprotonation of the amino units of chitosan and the swelling of the
films decreases. In addition, the hydrophobic side-chain aggregation and hydrogen bonds

CS NH + CS NH 2

CS NH +

CS NH 2

CS NHOC hydrophobic side CS NHOC hydrophobic side

chains chains

In pH < 6.5-6.7 buffer In pH > 6.5-6.7 buffer

Figure 5.2
Structure change of the chitosan graft copolymer in acidic and alkaline buffers.