Formation of Chitosan-Based Hydrogels Network - Chitosan Based Hydrogels: Functions and Applications - page 183

degree of N - acetylation of chitosan increases. For a given chitosan sample, the higher the
pH, the lower the alginate content of the PEC [25]. And the ratio of chitosan to alginate is
independent of the M W of chitosan and the composition of alginate used [26,27].
In order to fabricate homogeneous chitosan-alginate PECs films, chitosan and alginate
solutions are mixed under controlled conditions to yield fine coacervates that are isolated
from the reacting pot and resuspended in dilute CaCl 2 solutions prior to casting and dry-
ing. This method has the advantage of using an aqueous system, which is stable to storage
at ambient conditions, to produce water-insoluble homogeneous membranes [28]. Increasing
the CaCl 2 concentration does not affect membrane thickness, but improves the respective
mechanical properties [29]. The mechanical strength decreases with increasing the content
of chitosan in the PECs, which is due to the inhibition of chelation of calcium ions with
alginate chains at high concentrations of chitosan. The pH value is another factor influenc-
ing the mechanical strength of chitosan-alginate PECs. Sankalia et al. [30] found that
chitosan-alginate PECs, which are formed when a chitosan solution with pH 2 and an alg-
inate solution with pH 6.5 are mixed, show excellent mechanical strength. The maximum
interaction between the amino and carboxyl groups takes place under this condition and
results in a compact film. Iwasaki et al. [31] and Tamura et al. [32] found that the chitosan-
alginate scaffolds are stable regardless of the pH value of the solution. That can be attrib-
uted to (1) the interaction of amine groups on chitosan with carboxyl groups on alginate,
which prevents the protonation of amino groups on chitosan, and (2) the carboxyl groups
on alginate that buffer the solution and slow down the degradation of chitosan [33].
Chitosan-alginate PECs show good compatibility in vitro with the mouse/human fibro-
blasts, osteoblasts, and chondrocytes [34]. The chondrocytes on chitosan tend to form a
monolayer, a possible marker of chondrocyte dedifferentiation and fibroblastic phenotype
[35,36]. In contrast, the chondrocytes on chitosan-alginate PECs materials form much
larger cell clusters. And cell proliferation on chitosan-alginate scaffolds is found to be
faster than that on a pure chitosan scaffold [37]. In addition, chitosan-alginate PECs have
the advantage of not destroying the drug structure loaded. This characteristic is especially
suitable for the encapsulation of biological products with low stability, such as peptides,
proteins, vaccines, and so on [38]. The chitosan-alginate PECs are also an effective con-
trolled release carrier for nerve growth factor [39].
4.2.1.3 Chitosan/HA PECs
Chitosan/HA PECs are prepared by mixing the chitosan solution and the HA solution
below the p K a value of chitosan (6.5). Denuziere et al. [40] have reported that a PEC com-
posed of HA and chitosan can be formed below the p K a of HA because the ionic interac-
tion between the polyions competes with the protonation of HA. The chitosan/HA PECs
are most stable at pH values around neutrality, and are more labile in acidic than under
basic conditions [41]. At the initial ionic state of polyions dissolved in formic acid, the
amino groups of chitosan interact with formic acid and the carboxyl groups of HA existing
in a protonated form. As the pH of the solution increases, protonated carboxyl groups
competed with the precomplexed amine groups of chitosan with formic acid to form an
ionic linkage between HA and chitosan [42].
The swelling degree of chitosan/HA PEC films ranges between 250% and 325% and
changes in relation to the chitosan content of the network. An increase in the chitosan frac-
tion of the films leads to an increase in the equilibrium swelling ratio [43]. This behavior
may be due not only to the ratio of chitosan and the HA complexation of the network, but
also to the chitosan content having a large number of water-binding sites [44]. Moreover,