Application of Chitosan-Based Biomaterials in Tissue Engineering - Chitosan Based Hydrogels: Functions and Applications - page 425

6-sulfate, dermatan sulfate, and heparan sulfate). The fibroblast is most prevalent in the
dermis and is responsible for synthesizing and depositing collagen fibers in continuous
networks that form the structural scaffold. Research into dermal tissue engineering is
developing based on the research and application of the epidermal cover. Tissue-engineered
dermal equivalents have been developed that can be used alone or in combination with
epithelial sheets as for the treatment of large full-thickness skin defects. For successful
dermal engineering, both selection of a suitable porous scaffold and optimization of cell
seeding are important. Chitosan-based biomaterials, especially chitosan-GAG composites,
can be selected for the construction of artificial dermis in vitro , which could be composed
to mimic the mechanical characteristics of the dermis and have cytocompatibility for fibro-
blasts. Moreover, fibroblast ingrowths promote the substitution of these chitosan-based
biomaterials with appropriate biodegradation properties by natural components of the
dermis. An ideal chitosan-based scaffold used for dermal replacement should possess the
characteristics of excellent cytocompatibility for fibroblasts, suitable microstructure such
as 100-200 μm mean pore size and porosity above 90%, controllable biodegradability and
suitable mechanical property [102].
It has been shown that fibroblast-specific ECM components, such as type-I collagen and
GAGs, play a critical role in regulating the expression of the fibroblast phenotype and in
supporting both the migration and proliferation of fibroblasts. Chitosan could serve as a
GAG analog component as it contains N -acetyl-glucosamine groups in the molecule.
Therefore, collagen is usually introduced in the chitosan network to modulate the cell
behavior of fibroblasts and further construct the dermal equivalent. Moreover, gelatin is
the partial derivative of collagen and has been processed into composites by blending with
chitosan for the construction of dermal equivalent. To better simulate the structures of
the dermis, some GAGs or amino acids are combined into the chitosan-collagen scaffold
[103-105]. In addition, other chitosan-based dermal equivalents are also studied. Hybrid
nanofibrous films of chitosan and poly(lactic- co -glycolic acid) (PLGA) have been widely
studied. The chitosan-PLGA scaffold has controlled mechanical properties and degrada-
tion behaviors. Moreover, it can improve the proliferation capacity of human embryo skin
fibroblasts. It is a potential scaffold for skin tissue engineering. However, there are few
reports on the in vivo test of the chitosan-PLGA nanofiber scaffold. There are also many
difficulties that need to be overcome [106,107].
As the dermal equivalent, chitosan-based biomaterials should have the following pro-
perties: First, an appropriate microstructure of the chitosan-based porous scaffold is the
basic element for obtaining an artificial dermal equivalent. The scaffold was indeed
composed of chitosan and collagen, which were evenly dispersed through the scaffold.
The pores of pure collagen porous scaffold usually collapse owing to the low hardness of
collagen. Chitosan can improve deformation-resistance ability and reduce pore collapse
because of the stiffer molecular structure of chitosan. Gao et al. [107] found that the pore
size on the surface of chitosan-collagen films improved with increasing chitosan percentage.
Higher chitosan (>50%) contents can yield a surface with larger pores. Of course, the micro-
structure of the scaffold is also controlled by the preparation method. In addition, cross-
linking is necessary in this system. The chitosan-collagen or chitosan-gelatin scaffolds
quickly degraded and cannot keep the original shape if there is no cross-linking between
collagen (gelatin) and chitosan. At present, glutaraldehyde, 1-ethyl-3-(3-dimethylamino-
propyl)-carbodiimide/ N -hydroxyl-succinimide, genipin, and so on are employed to prepare
the chitosan-collagen scaffold. Second, the growth behaviors of fibroblasts in scaffolds
are also very important for the construction of dermal replacement. Chitosan-collagen
scaffolds can improve the proliferation of fibroblasts compared with pure chitosan