Application of Chitosan-Based Biomaterials in Tissue Engineering - Chitosan Based Hydrogels: Functions and Applications - page 440

+ =

Scaffold Cells Cell + scaffold

constructs

Engineered bone tissue in
the defected site of long bone

Figure 9.31
Schematic diagram of the bone tissue engineering approach using scaffolds and cells. (From Thein-Han, W. W.
et al. 2008. Mater Sci Technol 24: 1062-1075. With permission.)

osteoblast-osteoclast coculture system compared to osteoclasts. In this coculture system,
osteoblasts are responsible for the generation of bone ECM but also regulate the differen-
tiation and activity of osteoclasts.
Chitosan-based scaffold is an attractive candidate for bone because it can modulate osteo-
blast and osteoclast growth and differentiation, and matrix mineralization. But, as a tempo-
rary template introduced at the defective site or lost bone for tissue regeneration, which
over a period of time gradually degrades and is replaced by newly formed bone tissue, the
chitosan-based scaffold should also have other characters as follows: (1) An ideal bone tis-
sue-engineering chitosan-based scaffold should have an appropriate microstructure for the
growth of osteoblasts. On the basis of an osteoblast length of approximately 10-30 μm, the
pore diameter of the chitosan-based scaffold should be higher than this value. In general,
the pore size should range from 100 to 400 μm. When pore diameter is too small, cells may
provoke pore occlusion and prevent cellular penetration within the scaffold: pore size rang-
ing from 75 to 100 μm resulted in ingrowth of unmineralized osteoid tissue and smaller
pores (down to 10 μm) were penetrated only by fibrous tissue [165]. (2) The chitosan-based
scaffolds should have sufficient mechanical strength during in vitro culturing to maintain
the spaces required for osteoblast ingrowth and matrix formation. Moreover, it can bear
certain loading after in vivo implantation. The optimal mechanical strength of the chitosan-
based scaffold should be close to the mechanical strength of natural bone. For example, the
compressive strength of cortical bone is 130-180 MPa and the compressive strength of can-
cellous bone ranges from 4 to 12 MPa. At present, the compressive strength of some chito-
san-based scaffolds mimics cancellous bone, but to obtain a compressive strength similar to
cortical bone is very difficult. (3) The degradation of the chitosan-based scaffold should
match with the formation of new bone. In general, it needs ca. 1-6 months according to the
age and constitution of the patient. (4) Moreover, the scaffold should load and release vari-
ous growth factors (BMPs and TGF-β1) to improve the formation of new bone. In short,
mimicking the composites and structure of natural bone is an effective method to obtain
ideal chitosan-based bone engineering. At present, some proteins, polysaccharides, syn-
thetic polymers and inorganic minerals (HAp, calcium phosphate, etc.) have been incorpo-
rated into the chitosan network to construct artificial bone.

9.5.4.1 Chitosan-Based Polymeric Porous Scaffolds

Collagen and chitosan have intrinsic properties that support growth and differentiation of
osteoblasts. Osteoblasts have a specific affinity for collagen fibers. The incorporation of
collagen into a collagen-chitosan scaffold can increase the biological stability and adjust the
degradation behaviors. Chitosan-collagen composite sponges promoted growth of osteo-
blasts into the mature stage. Moreover, osteocalcin and calcium were clearly demonstrated