Formation of Chitosan-Based Hydrogels Network - Chitosan Based Hydrogels: Functions and Applications - page 195

interconnected 3D porous structure of the scaffolds is retained. However, the mean pore
size increased from ca. 100 μm (the uncross-linked) to >200 μm (the uncross-linked). At the
same time, more sheet-like structures appear together with condensed walls.
The chitosan/collagen networks cross-linked by GA show excellent biocompatibility not
only in vitro but also in vivo [114-116]. Therefore, it is widely used in tissue engineering, espe-
cially for skin tissue engineering and it is also used as a new wound-dressing material for
damaged tissue recovery in various organs. The system has been explored to optimize the
matrix for efficiently delivering it to and stably localizing it in the target tissues of fibroblast
growth factor (FGF) [117]. The chitosan/collagen cross-linking nanofiber network is pre-
pared by adding the synthetic polymer poly(ethylene oxide) (PEO), because collagen and
chitosan cannot form nanofibers during electrospinning due to their larger net charges. The
water sorption ability of the nanofiber network decreases after cross-linking [116]. Tsai et al.
[118] found that chitosan/collagen network scaffolds with glutamic acid molecules as cross-
linking bridges can enhance the tensile strength and improve cytocompatibility with skin
fibroblasts, because the glutamic acid molecules to form cross-linking bridges might cause
the chitosan/collagen-glutamic acid surface to absorb more serum proteins in the culture
medium. The N , O- (carboxymethyl) chitosan/collagen cross-linking networks are more effi-
cient in accelerating wound healing, because the N , O- (carboxymethyl) chitosan is able to
stimulate the migration of fibroblasts, and the migration is significantly enhanced by N , O-
(carboxymethyl) chitosan in a concentration-dependent manner [119]. In order to reduce the
cell contraction and improve the initial cell distribution in chitosan/collagen scaffold, Tan
and coworkers [120] developed a perfusion seeding system for dermal fibroblasts seeding
onto collagen/chitosan sponges. High seeding efficiencies with uniform cell distributions
are achieved by the perfusion seeding method, which further facilitates cell proliferation.
Combining the chitosan-cross-linked network with collagen is also able to improve the
biological stability and strength of collagen to satisfy the demand of applications in bone
tissue engineering. The incorporation of chitosan into a collagen scaffold increases the
mechanical strength of the scaffold and reduces the biodegradation rate against collage-
nase [121,122]. Osteoblasts show higher levels of markers of osteoblastic differentiation at a
mature stage, osteocalcin and calcium, in the chitosan/collagen network than chitosan.
There are several possible reasons for this: first, osteoblasts have a specific affinity for col-
lagen fibers; second, the stimulating effect of collagen matrix is further enhanced by the
three-dimensional structure of the scaffolds; and third, chitosan improves the internal
porous structure of a chitosan/collagen composite [123].
Collagen also greatly influences hepatocype growth and stability of mRNA for the
expression of liver-specific function. Therefore, chitosan/collagen cross-linking network
films are capable of maintaining both the attachment and function for hepatocutes [99].
4.3.1.1.2 Chitosan/Gelatin Hybrid Cross-Link Network
Chitosan/gelatin cross-linking networks are attractive for their applications in controlled
release devices and tissue engineering. These networks are prepared using many cross-
linkers, such as TPP, GA, genipin, EDC, and so on. In general, for chitosan/gelatin cross-
linking networks, the mechanical properties improved with increasing cross-linking
density. On the other hand, an increase in cross-linking density will induce a decrease in
swelling and pH sensitivity. Thus, there is a practical trade-off between mechanical integ-
rity and pH sensitivity, and both of these qualities are affected by the amount of chitosan,
gelatin, and cross-linker as well as the pH at which curing is performed [124]. Chitosan/
gelatin-cross-linked networks have a higher degradation rate and more loss of material
than chitosan-cross-linked networks. Mechanical properties are affected by the addition