Hyaluronic Acid Hydrogel: A Favourable Niche for Neural Stem Cells - Hyaluronic Acid for Biomedical and Pharmaceutical Applications - page 12

spread much faster and more extensively in hydrogels with a higher
density of RGD [54]. Furthermore, the mechanical properties of the
HA hydrogel may influence the cell spreading, and this is highlighted
by the work which shows a clear relationship between modulus and
cell migration/proliferation on RGD-functionalised HA-polyethylene
glycol gels [55].
1.4.3 Cell Survival, Proliferation and Differentiation
As mentioned above, the survival, proliferation and differentiation
of the NSC are regulated by several factors in the ECM, i.e., all the
components, together with the stiffness and topography of the ECM
play a role [31]. It is apparent therefore, that HA hydrogels would
modulate NSC proliferation and differentiation to form neurons or
glial cells, as shown by studies of Pan, Ren and their co-workers
[50, 51]. For instance Figure 1.4 [51] shows the differentiation
of NSC, cultured in the HA-polylysine hydrogel, into β-tubulin
III-positive neurons ( Figure 1.4a ) and glial fibrillary acidic protein-
positive glial cells ( Figure 1.4b ).
The proliferation and differentiation of the NSC on HA hydrogels
are also affected by the mechanical properties of the materials, the
elastic modulus in particular. With regard to the elastic modulus of
HA hydrogels, it is reported that a decrease of NSC proliferation is
dependent on the increase of the gel modulus [20-22]. Moreover,
the stiffness of HA gels also influences the differentiation of NSC,
indicating that the softer hydrogels, whose elastic modulus is more
similar to that of brain tissues, may enhance the rate of neuronal
differentiation [56]. The same results are obtained from a study which
shows that the mechanical properties of HA hydrogels influence the
differentiation of ventral midbrain-derived neural progenitor cells
encapsulated in the gels. The majority of neural precursor cells may
differentiate into neurons with a relatively mature phenotype, i.e.,
with more and longer branched processes, if they are cultured in a
hydrogel with the mechanical properties comparable to those of the
neonatal brain. In contrast, most of the cells would differentiate into