Application of Chitosan-Based Biomaterials in Tissue Engineering - Chitosan Based Hydrogels: Functions and Applications - page 416

Material

Chitosan

Architecture

Cells may spread
and proliferate

2D

3D

Cells do spread
and proliferate

Figure 9.13
Schematic diagram showing the cell colonization characteristics on different architectures. (From Huang, Y.,
Siewe, M., and Madihally, S. V. 2006. Biotechnol Bioeng 93: 64-75. With permission.)

due to the difficulty in crossing large bridging distances. However, the 3D-based chitosan
scaffolds cannot completely simulate the microenvironment of cell growth in vivo , which
may dissipate some functional expression during the process of cell culture in vitro . And
the application of the implanting chitosan-based 3D scaffold must be via surgery.
Chitosan-based injectable scaffolds for cell encapsulation or cell/hydrogels are promis-
ing substrates for tissue engineering because of in vivo culture environment, minimal
invasion, low cost, and so on. There are several criteria that must be considered. Cells are
suspended in a liquid precursor solution prior to encapsulation. The liquid precursor
loaded with targeted cells can be injected into the damaged site and experiences a gel
transition in situ due to physical or chemical stimuli. The process by which gelation occurs
must be mild and cell friendly. The hydrogel's structure and chemistry composites must be
suitable for cell survival and tissue formation, while its degradation must closely follow
tissue growth. Finally, the degradation products must not adversely affect encapsulated
cells ( cf. Figure 9.14) [64]. Recently, layer-by-layer (LBL) encapsulation of cells has been
developed. Briefly, a first layer of cells is grown on a surface to confluence, and then a
hydrogel precursor solution is deposited over the confluent cells and hardened via envi-
ronment stimuli. A second layer of cells is grown on top of the first layer of hardened
hydrogel followed by hardening of a second hydrogel layer on the second layer of cells; the
alternate deposition of cells and hydrogel is repeated several times to build a thick tissue
( cf. Figure 9.15). The LBL cell/hydrogel buildup can potentially allow higher density, better
alignment of cells, or construction of multicell-type tissues [65]. However, there are some
disadvantages of chitosan-based injectable scaffolds for cell encapsulation. (1) Chitosan
liquid precursor solution is not suitable for cell survival, because chitosan can dissolve in
acidic medium but apparently it is less favorable for the cells. Therefore, some chemicals
modified or composite with other polymers are necessary to modulate the pH value of the
precursor solution. (2) The mechanical strength and shape stability of cell encapsulation or