Formation of Chitosan-Based Hydrogels Network - Chitosan Based Hydrogels: Functions and Applications - page 188

is also expected to improve the hydrophilicity of the cross-link network. For exam-
ple, the chitosan network cross-linked by sulfosuccinic acid maintains the hydro-
philic performance [77].
2. Swelling behaviors : In general, the swelling process of cr-CS-based biomaterials
includes two stages: physical movement along free volume cavities of the net-
work and the formation of bond water with hydrophilic groups of the covalent
cross-linking network [78]. The swelling performance could be controlled by the
following factors: first, the concentration of the chitosan acetic solution during
the formation of the network is an important factor; the equilibrium degree of
swelling increases as the concentration decreases. It can be explained that the
intermolecular cross-linking reaction with the cross-linker decreases in the
dilute solution, but the intramolecular cross-linking increases. Second, the cross-
linking density also influences the swelling behaviors; the swelling degrees are
suppressed with increasing cross-linking density. For example, the degree of
swelling of chitosan fiber decreases as the concentration of cross-linker increases
[79]. Third, the type and amount of other compounds in the cross-linking system
are not ignored factors. For example, the swelling degree of the chitosan-poly-
ether-cross-linked network decreases with increasing the polyether amount,
which is due to the intensification of hydrogen bonding between chitosan and
polyether [80-84].
3. Degradation performance : The degradation rate of cr-CS-based biomaterials is much
lower than that of noncross-linked composites [85]. The cross-linked network may
have a high stereohindrance for the penetration of lysozyme and the steric effects of
the cross-linked chain among chitosan molecules, and it prevents lysozyme from
binding to the chitosan substrate. In general, with increasing the cross-linking den-
sity, the degradation rate decreases. Actually, the decrease of the mobility of the chi-
tosan chain can result in a low rate of solvent expulsion, and thus a low rate of mass
loss too [86]. Compared with bulk cross-linking, after surface cross-linking there are
fewer cross-linking agents left in the modified materials. Meanwhile, surface cr-CS-
based biomaterials show a lower initial degradation rate because the constructed
matrix begins to degrade from the cross-linking surfaces, but the degradation rate
increases with the time because of lower cross-linking extent inside the matrix [87].
4. Mechanical properties: Cross-linking can enhance the mechanical properties of the
chitosan-based biomaterials without impacting on the biocompatibility. One can
modulate the mechanical performance via controlling the cross-linking density or
the type and counts of other compounds in the composites systems. Du and
coworkers [88] found that the proper cross-linking density is able to improve the
mechanical properties of chitosan network films. For chitosan-based biomaterials
scaffold fabricated through thermally induced phase separation and freeze-drying
technology, the freezing temperature and concentration of acetic acid are also an
important factor to influence the mechanical performance [89]. Most cells can
sense biomaterials' intrinsic mechanical environment and the substrate or scaf-
fold rigidity/stiffness can also serve as an intrinsic mechanical stimulus. Stiffer
surfaces could promote the cell proliferation and the preservation of morphology.
For example, about 90% of the chondrocyte cells on uncross-linked chitosan films
have a spherical morphology and nebulous, punctate actin, while they are flat-
tened with stress fibers and 40-50% of cells have a flattened morphology on the
cr-CS films [90-92].