The Emerging Applications of Graphene Oxide and Graphene in Tissue Engineering - Biomimetics: Advancing Nanobiomaterials and Tissue Engineering - page 290

investigated. The chemical synthesis, functionalization, and even physical
processing of GO and graphene also need to be precisely controlled to
obtain functional materials whose size, size distribution, physical mor-
phology, and chemical properties are accurate. The latter parameters have
been shown to exert a signifi cant infl uence on the cytotoxicity and interac-
tions of GO and graphene with living systems. As an example, Akhavan
et al. recently reported that graphene nanosheets displayed a size-
dependent cytotoxicity and genotoxicity upon exposure to human MSCs.
These authors synthesized reduced GOs and graphenes with different lat-
eral dimensions ranging from ~11 nm to ~3.8 μm through the reduction of
polyethylene glycol-functionalized GO with hydrazine and bovine serum
albumin, and observed a direct relationship between the lateral dimension
of reduced GO and its cyto- and genotoxicity [96]. In vitro toxicity of gra-
phene-based materials is largely related to damage in the cell membrane
and oxidative stress. Note that precise control of the GO and graphene
patches to obtain well-defi ned sizes of graphene sheets with specifi c func-
tional groups is still a major challenge. Such an achievement would defi -
nitely help to fabricate more functional graphene-based materials for cell
therapy and TE, drug/gene delivery, and biosensing applications.
Micro- and nanofabrication methods provide invaluable tools to cre-
ate a desired and well-defi ned microenvironment that presents various
substrate characteristics (e.g., topography or roughness) to the cells and
enables the study of various cell behaviors [97]. As an example, Wang
et al. reported the use of inkjet printing technology to create microscale
lines of polydimethylsiloxane (PDMS) on fl uorinated graphene to obtain
aligned MSCs [4]. Here, substrates that controlled the alignment of MSCs
increased the differentiation effi ciency of the cells toward neuronal cells
compared to those with randomly distributed cells. The use of GO and
graphene with microfl uidic [98] and electrospinning [99] technologies
could further reveal the potential advantages of these materials to fabri-
cate 3D and hierarchically organized scaffolds. Note that structurally orga-
nized scaffolds play a crucial role in providing suitable cues for the cells to
organize themselves at the microscale. Microorganization of cells in 3D is
essential to obtain organized and functional tissue constructs mimicking
the corresponding tissues in vivo . Taken together, further combinations of
micro- and nanotechnologies with graphene-based materials may provide
an opportunity to create more functional materials for TE applications.
Finally, graphene-based materials can be engineered to obtain biomi-
metic structures referred to as biomimetic graphene structures. For exam-
ple, graphene-based materials have already been used to mimic butterfl y
wings [48], rose petals [49], honeycomb [50], and nacre [51]. These struc-
tures are of great interest for both fundamental and applied research [52].
The concept of biomimetic graphene appears to be based on the following
Leonardo da Vinci quotation: “Where nature fi nishes producing its own