Application of Chitosan-Based Biomaterials in Tissue Engineering - Chitosan Based Hydrogels: Functions and Applications - page 452

the layers. However, the optimal scaffold should have continuous pore gradients. However,
it is usually difficult to fabricate well-constructed scaffolds with continuous gradient pore
sizes and porosities using common processing techniques, such as particulate leaching
and freeze-drying technology. RP can accurately control the microstructure of chitosan-
based scaffolds. But the porosity is low; for example, the porosities of 3D scaffolds pre-
pared via 3D printing technology and fused deposition modeling technology are ca.
40-60% and 21-68%, respectively. Therefore, a suitable and meaningful design and
preparation technology to represent the continuous gradient that can fulfill the biological
and mechanical requirements of the regenerated tissue is needed.

9.6.2 Stem Cell Technology and Chitosan-based biomaterials

Recently, seed cells have become the main bottlenecks in the development of tissue engi-
neering. For example, the application of chondrocytes is restricted due to its limited sources
and weak capacity to maintain the chondrocyte phenotype and biological activity. Adult
stem cell types are pluripotent, meaning that they can differentiate into cells derived from
three germ layers. For example, hematopoietic stem cells may differentiate into brain cells,
skeletal, cardiac muscle cells, and liver cells. MSCs may differentiate into skeletal muscle
cells, may also differentiate into osteoblasts, chondrocytes, adipocytes, and other myo-
cytes such as cardiac muscle cells, and so on. The plasticity provides the basic possibility
for multiple-tissue engineering using a certain type of stem cells. In previous research,
some bioactive molecules were incorporated into the stem cell-scaffold system to stimulate
the differentiation of stem cells along the specific lineage ( cf. Table 9.6) [210]. Even without
differentiating into specific cells or tissues, the self-renewal aspect of MSCs can still pro-
vide a trophic effect in structure reparative environments. However, the applications of
these bioactive molecules are limited due to their high cost and side effects to some extent.
Therefore, it is a challenge to build an appropriate microenvironment for the proliferation
and differentiation of stem cells. Many researchers have employed biomaterial scaffolds
with different chemical signals, mechanical signals, and topographical signals to adjust
the differentiation behaviors of stem cells.
Chemical functional groups of biomaterials could influence the differentiation behav-
iors of MSCs, such as methyl (-CH 3 ), hydroxyl (-OH), carboxyl (-COOH), and amino
(-NH 2 ) groups that have been presented in biomaterials. Curran et al. [211,212] reported
that the -NH 2 and -SH modified surfaces of clean glass promoted and maintained
osteogenesis both in the presence and absence of biological stimuli, but these surfaces
did not support long-term chondrogenesis under any test conditions. Incorporating

TAble 9.6
Differentiation Supplements in the Medium for MSCs

Differentiation Type Supplements

Osteogenic differentiation Dexamethasone (Dex), l-ascorbic acid-2-phosphate (AsAP) or ascorbic

acid, β-glycerophosphate

Chondrogenic differentiation Dex, AsAP, TGF-β or BMP-2, BMP-6

Adipogenic 1-Methyl-3-isobutylxanthine, Dex, insulin, and indomethacin

Neuronal differentiation Transferring, putrescine, insulin, progesterone, selenium, retinoic and

brain-derived neurotrophic factor

Epidermal differentiation EGF, FGF, insulin, retinoic acid CalCl 2 or insulin, transferrin, and

selenite (ITS), Dex