The Emerging Applications of Graphene Oxide and Graphene in Tissue Engineering - Biomimetics: Advancing Nanobiomaterials and Tissue Engineering - page 287

than glia cells. Neural activity of differentiated cells was also recorded
through the electrical stimulation of the cells using the graphene as the
electrode. Functionalized graphenes have also demonstrated an excellent
potential to direct the stem cell fate. For example, fl uorinated graphene
enhanced the cell attachment, growth, and differentiation of MSCs into
neuronal cells through spontaneous cell polarization. This effect was more
profound in the presence of neuron-inductive agents (i.e., retinoic acid)
[4]. A rapid method based on inkjet printing was also developed to align
the MSCs on the graphene substrates. Such cellular alignment promoted
the neurogenesis even in the absence of growth factors for the differentia-
tion. Fluorinated graphene was likely used because the presence of fl u-
orine groups in pharmaceuticals improves their metabolic stability and
interactions with proteins due to its small size and high electronegativity.
Therefore, fl uorine is included in approximately 20% of all drugs, such
as Prozac, Lexapro, and Lipitor [85]. Graphene was also used to culture
and differentiate i PSCs [86]. i PSCs were fi rst introduced by the Yamanaka
group in 2006 [87], and their great promise for regenerative medicine was
recognized by the 2012 Nobel Prize in Medicine awarded to Professors
Gurdon and Yamanaka. They can be derived from the somatic cells using
a cocktail of genes that reprogram the somatic cells into i PSCs. This proce-
dure does not require the destruction of embryos and therefore avoids the
ethical problems related to embryo destruction. Chen et al. [86] demon-
strated that mouse i PSCs can adhere to and proliferate on GO more rapidly
than on graphene and glass slides, most likely due to the oxygen-contain-
ing functional groups of the GO, which facilitate cellular adhesion and
growth. Graphene was able to maintain i PSCs in an undifferentiated state,
while GO accelerated i PSC differentiation. Finally, both substrates led to
i PSC differentiation towards the ectodermal and mesodermal lineages.
The differences in stem cell behavior on GO and graphene substrates are
mainly attributed to the differences in surface chemistry between these
two materials. To keep the pluripotency of i PSC, they should be cultured
on feeder cells, such as mouse embryonic fi broblasts, with suitable soluble
factors, such as the leukemia inhibitory factors [88]. Without such sup-
porting materials, i PSC are spontaneously differentiated into embryoid
bodies followed by the development of various cell types. It is of great
interest to control the pluripotency of i PSC in the cell therapy and tissue
regeneration using simple, cheap, and reproducible procedures and mate-
rials, such as graphene substrates. Taken together, GO and graphene are
promising materials for studying stem cells and controlling their fate, and
represent a facile and inexpensive avenue for stem cell research, as large-
scale and high-quality graphene sheets can be fabricated at a low cost [89].
Although graphene possesses a high electrical conductivity, little work
has been conducted to exploit this unique property for TE applications.
As an example, Park et al. used a graphene substrate as the stimulating