Formation of Chitosan-Based Hydrogels Network - Chitosan Based Hydrogels: Functions and Applications - page 186

between chitosan and ion cross-linkers depend on the molecular structure of the ions [63],
these interactions can be modulated via adjusting the charge density of cross-linkers and
the pH value of solutions [64,65].
A phosphate anion, such as triphosphate (TPP), hexametaphosphate (HMP), and poly-
phosphate (PP), is usually used as a cross-linker for chitosan ( cf. Figure 4.4) [66]. The ionic
cross-linking density of the chitosan-TPP network or the interpolymer linkage of chito-
san-PP network can be adjusted by transferring the pH value of the cross-linking agent
from the basic to the acidic condition [67]. Chitosan solutions containing >20 wt% glycerol
phosphate become a gel at 37°C and maintain this form for 28 days in vitro and in vivo [68].
The mechanical strength of this system formed under the acid condition decreases com-
pared with that of the system formed under the basic condition. This can be attributed to
the tightening of the gel network by increased shrinking of this system [69].
The swelling is lower in the sodium tripolyphosphate (STPP)-anion-cross-linked chito-
san microspheres in comparison with the microspheres prepared with the sodium
hexametaphosphate (SHMP) anion cross-linker. This is due to the stronger electrostatic
interactions of SHMP-anion-cross-linked chitosan in comparison with STPP-anion-cross-
linked chitosan [66]. The SHMP anions show strong electrostatic interactions with ion-
ized chitosan, which provide sufficient opportunities to control the drug release pattern
of centchroman and to make it in a much better way than reported with other phosphate
cross-linkers [70].
The formation of a chitosan-glycerophosphate thermosetting gel mainly depends on the
hydrogen bonding, ionic interaction, and chitosan-chitosan hydrophobic interactions. This
system play an important role in successfully delivering biologically active GFs in vivo as
well as being an encapsulating matrix for living chondrocytes for tissue-engineering appli-
cations [71]. Hoyland and coworkers [72] investigated human mesenchymal stem cells
(hMSCs) differentiated to nucleus pulposus (NP)-like cells in temperature-sensitive
chitosan-glycerophosphate hydrogels. Here, cells can be mixed at room temperature prior
to sol-gel transition and give a homogeneous cell distribution. hMSCs cultured in gels for
4 weeks in standard media express a chondrocytes phenotype. While the chondrocytic
marker gene expression profile of MSCs is similar to both NP cells and articular chondro-
cytes, the MSCs synthesized and deposited ECM proteins within the gel in ratios that match
NP cells more closely than articular chondrocytes. Moreover, chitosan-glycerophosphate
hydrogels aid chondrogenic differentiation of MSCs and inhibit osteogenic differentiation

(PO 3- ) n
STPP ( )

Protonated chitosan

STPP cross-linked chitosan

(PO 6- ) n
SHMP ( )

SHMP cross-linked chitosan

Protonated chitosan

Figure 4.4
Formation chitosan cross-linking network via ionic cross-link using a phosphate anion. (From Gupta, K. C., and
Jabrail, F. H. 2007. J Appl Polym Sci 104: 1942-1956. With permission.)