Application of Chitosan-Based Biomaterials in Tissue Engineering - Chitosan Based Hydrogels: Functions and Applications - page 420

O

N 3 NH (CH 2 ) 5 CNH EGF

UV irradiation

N - N 3 • + N 2

Nitrene

O

EGF HN C CH 2 ) 5 HN NH chitosan

Figure 9.16
Production of nitrene groups in phenyl-azido derivatized EGFs by ultraviolet irradiation and immobilization
on chitosan surface. (From Karakecli, A. G. et al. 2008. Acta Biomater 4: 989-996. With permission.)

may not be sufficient to promote long-term implantation, because of drawbacks, including
protein desorption and/or exchange in contact with physiological fluid.
Growth factors or polymer microspheres containing growth factors can be directly
encapsulated in the chitosan-based scaffold to construct a bioactive scaffold for tissue
engineering. In this case, these growth factors are not free and the binding efficiency can
be accurately controlled. The interactions between growth factors and scaffolds are still
the main factors to affect the stability and release behaviors of growth factors. But growth
factors are not easily released from the chitosan-based scaffolds by a diffusion mecha-
nism. The dissolution and degradation of the scaffold itself in the biological environment
are the main driving forces for the delivery of growth factors. Therefore, the release behav-
iors can be controlled by the swelling and degradation properties of scaffolds [78].
Growth factors are also immobilized on the surface of chitosan-based scaffolds to
construct a bioactive material for tissue engineering. Chemical binding involves a covalent
attachment of the target molecule to the solid surface, resulting in irreversible binding
with high levels of surface coverage, which makes this approach more suitable.
Gumusderelioglu and coworkers [79] bound epidermal growth factors (EGFs) on a chito-
san film surface via photochemical immobilization ( cf. Figure 9.16). The immobilized
EGF activated the EGF receptor for a longer time, and a high mitogenic effect was
observed. Park et al. [80] immobilized bone morphogenetic protein-2 (BMP-2) on a chitosan
matrix using a bifunctional reagent succinimidyl 4-[ N -maleimidomethyl]cyclohexane-1-
carboxylate), which can react with chitosan on one end and BMP-2 on the other. The chemi-
cally bound BMP-2 remained bioactive and was more effective in stimulating osteoblastic
cell proliferation and differentiation as compared with the BMP-2-adsorbed chitosan matrix.

9.5 Application of Chitosan-Based Biomaterials in Tissue Engineering
Tissues can be defined as an assembly of cells surrounded by an ECM. In vertebrates the
main tissue types are vascular, skin, nerve, connective (bone and cartilage), and muscle