Biomedical Engineering Reference
In-Depth Information
approaches. The ideal biomaterial substance should mimic the natural environment
in the cartilage-specific ECM components (type II collagen and GAGs). Chitosan-based
biomaterials have been extensively tested as mimicking the cartilage matrix and are
considered promising candidates for the repair of articular cartilage due to the structural
similarity of chitosan to various GAGs.
N
-acetyl-glucosamine in chitosan is an important
ingredient of polysaccharide for chondrogenic expression. Chitosan has the ability to
maintain the round morphology of chondrocytes, which is a normal phenotypic character-
istic and preserves their capacity to synthesize cell-specific ECMs [124]. It has already been
shown that chondrocytes grown on chitosan films exhibit a spherical morphology and
express type II collagen and aggrecan [125]. However, the chitosan-based film is not appro-
priate for constructing artificial cartilage. Some chitosan-based hydrogels, porous scaf-
folds, or fiber scaffolds have been used to construct the artificial cartilage. There are three
principles during the process of design of the chitosan-based artificial cartilage: (a) the
composites should mimic the ECM of the cartilage-specific ECM; (b) the degradation rate
should match with the regeneration. Chondrocytes-laden pure chitosan used to repair
articular cartilage defects may proceed slower than the rate of cartilage regeneration; and
(c) the fundamental structure of a scaffold should be a 3D system with adequate mechanical
strength because articular cartilage is a mechanically stressed tissue. The material pro-
perties of articular cartilage are as follows: a compressive equilibrium aggregate modu-
lus of 0.5-1.2 MPa, a tensile equilibrium modulus of 15-40 MPa, and a permeability of
(0.5-5) × 10
−15
m
4
/(N s) [126].
9.5.3.1 Chitosan-Based Hydrogels-Chondrocytes Construct
Encapsulation of chondrocytes within the chitosan-based hydrogels is the main strat-
egy to construct the artificial cartilage. Lu et al. [127] have demonstrated that a chito-
san solution injected into the knee articular cavity of rats causes a significant increase
in the density of chondrocytes in the corresponding articular cartilage. Recent studies
have presented an initial attempt to elaborate injectable thermosensitive chitosan-
based hydrogels and to assess their potency to provide a substrate for
in vitro
and
in
vivo
neo-chondrogenesis. First, chondrocytes were mixed with the thermosensitive
chitosan-based solution. After gentle mixing, the suspension was incubated at 37°C for
several minutes to form a gel or injected quickly into the cartilage injury site. The
chondrocytes are encapsulated homogeneously. The gelation process does not compro-
mise cell viability and there is sufficient mass transport of nutrients and oxygen to the
cells inside. Differentiated chondrocytes are characterized by a round morphology.
Preserving this feature inside hydrogels is a prerequisite for efficient chondrogenic
matrix production. Chitosan-based hydrogels can provide the constrained environ-
ment for chondrocytes that closely mimics the natural state of chondrocytes in carti-
lage. Chondrocytes inside chitosan hydrogels still maintained a round morphology
after several weeks. Moreover, this “natural” environment may have stimulated the
synthesis of the original products of collagen type II and aggrecan found in chondro-
cytes [128-130]. Wang and coworkers [66] found that thermosensitive chitosan-β-
sodium glycerophosphate hydrogel could support matrix accumulation of chondrocytes
and could repair sheep cartilage defects in 24 weeks (
cf.
Figure 9.24)
.
On the other
hand, chemical cross-linking of chitosan-based hydrogels is also used to encapsulate
chondrocytes. However, some toxic cross-linking agents, such as glyoxal, glutaralde-
hyde, carbodiimide, and diepoxy compounds, cannot be used, because it is not imprac-
ticable to remove the residual cross-linking agents. Marra and coworkers [131] added
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