The Emerging Applications of Graphene Oxide and Graphene in Tissue Engineering - Biomimetics: Advancing Nanobiomaterials and Tissue Engineering - page 285

acid weakens the electrostatic repulsion force between GO sheets while
polymers add hydrogen-bonding sites on the GO sheets and consequently
increase the electrostatic interactions between the GO sheets [74].
Stem cells are able to self-renew and differentiate into various cell types.
Therefore, they have been extensively used in regenerative medicine to
engineer tissues and organs [78]. Both synthetic and natural materials
have been employed to transplant stem cells and to differentiate them into
specifi c cell lineages, such as bone, muscle, and neural cells. Physical and
chemical properties of used materials are crucial parameters for directing
the stem cell fate [79, 80]. Stem cells can be categorized into three main
types, consisting of: (i) adult stem cells that can be differentiated into spe-
cifi c cell types, (ii) embryonic stem cells derived from the inner mass of
blastocystes, and (iii) induced pluripotent stem cells ( i PSCs), a novel stem
cell type derived from somatic differentiated cells [81]. Graphene-based
materials have shown great promise to direct the fate of stem cells and to
elucidate the biological phenomena underlying these pathways. The rea-
son may be the simple physical structure and well-characterized chemical
composition of graphene and its derivatives, which allow precise evalu-
ation of stem cells on these substrates. For instance, graphene has been
shown to accelerate stem cell differentiation pathways, such as the differ-
entiation of human mesenchymal stem cells (MSCs) along the osteogenic
lineage, likely due to the mechanical properties and surface morphology
of graphene [82]. Interestingly, graphene-induced differentiation was as
effective as growth factor-induced differentiation, the common approach
used for stem cells [82]. Note that MSCs derived from the adult bone mar-
row are able to differentiate into various cell lineages, such as osteoblasts,
chondrocytes, and adipocytes. The mechanical properties and topogra-
phy of scaffolds and some growth factors can induce MSC differentiation
toward a specifi c cell line for biomedical applications. Successful MSCs
proliferation and rapid differentiation on the graphene substrates with-
out using specifi c growth factors hold great promise for bone regenera-
tion therapy using these cells because this approach tackles one of the
major challenges in this fi eld, that is the use and precise administration
of several growth factors. The latter method has been shown to fail when
it comes to the compatibility with implants, cost, and scalability [82]. Lee
et al. investigated the origin of favorable MSC growth and differentiation
on both GO and graphene substrates [83]. The results showed that MSC dif-
ferentiation to adipocytes on graphene substrates was largely infl uenced
by the high π-π adsorption and stacking of insulin on these substrates.
Insulin is a crucial factor for fatty acid synthesis and was denatured upon
adsorption on graphene, while GO interacted with insulin through weak
electrostatic bonding and therefore did not signifi cantly interfere with the
performance of insulin. Human neural stem cells were also observed to
differentiate at a higher rate on graphene substrates than on glass slides