25313.2.3 Physico-Chemical Approaches to Engineer the Niche
for Stem Cell Differentiation
One of the main objectives of using polymeric biomaterials in stem cell technology
is to direct the cell differentiation into a specific cell lineage. However, the complex-
ity and dynamic nature of the stem cell niche requires that a number of physico-
chemical stimuli should be incorporated in the material design to achieve a positive
outcome. For instance, a material designed for neural tissue regeneration would
require a polymer of low stiffness (100–500 Pa), whereas bone applications benefit
from composite materials (polymer and inorganic bioactive ceramics) mimicking
the native composite nature of bone itself.
13.2.3.1 Neurogenic Lineage
Over the past decade significant developments have been made in combining neural
stem cells (NSCs) with natural or synthetic polymeric biomaterials. In particular,
nanofiber scaffolds or hydrogels combined with stem cells and growth factors are
being developed to tackle neurological diseases. Nanofiber scaffolds are attractive
in neural regeneration because they create aligned neural tissue similar to the native
one. Using these nanofiber scaffolds, stem cell differentiation can be controlled by
the orientation and diameter of the fibres (Sperling et al. 2017 , see Fig. 13.3), 2D
versus 3D configurations (Jakobsson et al. 2017 ), and polymer chemistry (Saha
et al. 2008 ). Synthetic polymers such as PLA (Soleimani et al. 2010 ), PLGA
(Kramer et al. 2011 ) and their co-polymers (Bini et al. 2006 ) are extensively used as
the base materials for fabricating nanofiber mats for neural tissue engineering.
These polymers are biodegradable, can be functionalized and spun into ultrafine
continuous fibres that closely resemble the extra cellular matrices.
On the other hand, hydrogels play a significant role in neural transplantation
because stem cells can be mixed with the biomaterial in a liquid form and induced
to gel following targeted injection in vivo. Hydrogels are also porous structures that
facilitate nutrient and oxygen transport and their mechanical properties can be tuned
to suit the application requirements. In the presence of the appropriate growth fac-
tors, hydrogels can be employed to direct the differentiation of neural stem cells.
These growth factors can be either chemically grafted on the polymeric backbone or
simply physically entrapped in the network. Examples of hydrogels used for dif-
ferentiation of neural stem cells include those based on natural polymers such as
collagen (Huang et al. 2013 ; Yuan et al. 2014 ), hyaluronic acid (HA) (Liang et al.
2013 ; Preston and Sherman 2011 ) and hyaluronan derivative (Moshayedi and
Carmichael 2013 ), or synthetic polymers such as PEG (Mckinnon et al. 2013 ), and
polyurethane (Hsieh et al. 2015 ). In recent years, a new class of “smart” synthetic
polymers, conducting polymers (CPs), is being explored for scaffold fabrication for
nerve regeneration. CPs are conjugated polymers capable of conducting electrons.
Coupled with their organic nature that matches the mechanical properties of tissue,
13 Current Technologies Based on the Knowledge of the Stem...