Application of Chitosan-Based Biomaterials in Tissue Engineering - Chitosan Based Hydrogels: Functions and Applications - page 441

in chitosan-collagen sponges but not chitosan scaffold. The collagen matrix promoted
osteoblastic differentiation and enhanced the osteoconductivity of chitosan-collagen scaf-
fold. Thus a combination of collagen and chitosan matrices should create an appropriate
environment for growth and differentiation of osteoblasts [166]. Moreover, combined chi-
tosan-collagen scaffold promoted osteogenic differentiation of MSCs due to the specific
cell-binding sites (particularly the RGD (Arg-Gly-Asp) amino acid sequences) of the colla-
gen matrix. But the pure chitosan scaffolds do not have this effect [167]. The defect sites
exhibited marked bone formation at the defect margin, and dense, fibrous connective tis-
sues were observed in the center of the defect at 8 weeks after implanting chitosan-colla-
gen in a rat calvarial defect [168]. However, the pore size and interconnected pore structure
of the chitosan-collagen scaffold need to be improved through the fabrication process.
Chitosan-alginate porous scaffolds are highly porous with a pore size around 100-300 μm,
a structure favorable for cell attachment and new bone tissue ingrowth. Compared with
pure chitosan scaffolds, chitosan-alginate scaffolds can improve the proliferation and
mineral deposition of osteoblasts. A layer of small particles (calcium-rich minerals) cov-
ered the cells grown on the chitosan-alginate scaffold. Moreover, chitosan-alginate scaf-
folds promoted rapid vascularization and deposited connective tissue and calcified matrix
within the entire scaffold structure [169]. For a porous chitosan polymeric scaffold, although
they have excellent bioactivity for osteoblasts, the compressive moduli of these scaffolds
were in the lower range of the trabecular bone, making them unsuitable for load-bearing
bone tissue-engineering applications.
Chitosan-based polymeric microsphere scaffolds have excellent mechanical properties.
Chitosan-poly(lactic acid-glycolic acid) (chitosan-PLAGA) sintered microsphere scaffolds
had compressive moduli (340.96-412.37 MPa) and compressive strengths (9.68-13.32 MPa)
in the range of the trabecular bone and compressive strength, and it can support well the
proliferation of osteoblasts [33]. Heparinized chitosan-PLAGA microsphere scaffolds with
low heparin loading are capable of stimulating MC3T3-E1 cell proliferation differentiation.
In vivo study using the rabbit ulnar critical-sized defect mode demonstrated that scaffolds
supported normal bone formation via intramembranous formation ( cf. Figure 9.32) [170].
However, the porosity of these chitosan-based microsphere scaffolds is only ca. 30%, which
may restrict the ingrowth of cells and exchange of nutrition. Therefore, enhancing poros-
ity is a crucial factor for the application of chitosan-based microsphere scaffolds in bone
tissue engineering.
9.5.4.2 Chitosan-Ceramic Composite Scaffolds
The components of bone possess a nanocomposite structure interwoven in a 3D matrix. In
recent years, nanomaterials have been developed for bone tissue engineering applications.
From the biomimetic point of view, chitosan-ceramic composites could potentially improve
both biocompatibility and mechanical properties of bone grafting materials. Chitosan-
HAp composite scaffolds have received great attention because they can mimic the com-
posites and structure of nature. In this system, HAp cannot be absorbed but it may be
inserted into new bone following the absorption of the chitosan. Chitosan-HAp composite
scaffolds were characterized by a highly porous structure and the pore size (50-120 μm)
was in a similar range for the scaffolds with different contents of nHAp. The compressive
strength of the chitosan-HAp scaffold increases with increasing HAp content in compos-
ites. Osteoblasts on the chitosan-HAp scaffold exhibited significantly higher proliferation
capacity than that on pure chitosan scaffolds [171]. Chitosan-HAp scaffolds significantly
enhanced osteoblast matrices in vitro , as evidenced by increased osteocalcin production