Biomedical Engineering Reference
In-Depth Information
characteristics apply strongly to many different kinds of tissue engineering, including but not limited
to bone, cartilage, and nerve.
Because graphene makes up carbon nanotubes, it is possible to create graphene by “unzipping”
carbon nanotubes, a fact that Akhavan et al . took advantage of. They used a silicon dioxide (SiO 2 )
matrix doped with titanium dioxide (TiO 2 ) nanoparticles as a photostimulation agent to utilize un-
zipped MWCNTs to form a graphene nanogrid atop a matrix. The researchers then tested the cellular
response to this material using human neural stem cells cultured for 3 weeks. Neural stem cells re-
sponded favorably to the growth surface, proliferated faster, and had a strong affinity toward neuronal
differentiation lineages when grown on the graphene nanogrids. Additionally, the TiO 2 nanoparticles
accelerated differentiation in the neuronal lineage when exposed to flash photo stimulation ( Akhavan
and Ghaderi, 2013 ). The experiment showed that graphene can not only improve neuronal differentia-
tion from neural stem cells, but also work in concert with TiO 2 nanoparticles, strongly implying that
it is possible to synergistically couple graphene with other nanomaterials for enhanced performance.
The high mechanical strength of graphene leads one to think of it as an ideal material for bone and
cartilage tissue engineering, but it inherently lacks sufficient 3D structure for use as a bulk material in
tissue engineering. One lab has developed a method to fabricate graphene foams, circumventing this
typical problem. First, nickel foam was created and used as a substrate to grow graphene via vapor
deposition. The nickel was then dissolved away, leaving behind a 3D structure made entirely of mul-
tilayer graphene nanomaterials. Cell viability was observed over 14 days of culture, and osteogenic
factors were measured at the conclusion of the 2 week period by fluorescent staining of osteopontin
and osteocalcin ( Crowder et al . , 2013 ). The graphene foams not only supported MSC attachment, but
also spontaneously promoted osteogenesis without the addition of any osteogenic factors in the growth
media ( Crowder et al . , 2013 ). This is significant as it demonstrates the ability of graphene in particular
to upregulate specific differentiation pathways without delivery of additional chemical cues.
A recent study performed in our lab showed that electrospun PCL fibrous scaffolds with incorpo-
rated carbon nanotube/graphene could have a powerful effect on MSC fate as well. The scaffolds with
carbon nanomaterial exhibited greatly increased MSC growth and glycosaminoglycan synthesis when
compared to control, indicating great potential for cartilage repair ( Holmes et al . , 2014b ).
1.2.2 SELF-ASSEMBLING NANOBIOMATERIALS
Since natural tissues are constructed via a bottom-up self-assembly process, scientists are attempting to
emulate natural ECM assembly via an emerging class of nanobiomaterials. These nanobiomaterials can
self-assemble in situ from constituent groups into complex 3D structures on the nano and micro scale,
and hold great potential to facilitate the construction of complex, biomimetic tissue environments in a
highly reproducible manner ( Huebsch and Mooney, 2009 ). The sheer number of self-assembling nano-
biomaterials is quite large and includes collagen, DNA, RNA, peptides, and many more ( Zhang, 2003 ).
Several self-assembling nanobiomaterials of particular interest will be discussed next.
1.2.2.1 Self-Assembling Nanotubes
Rosette nanotubes (RNTs, Figures 1.3 A-B) are a new class of biologically inspired supramolecular
self-assembling nanomaterials. It consists of repeating units of DNA base pairs (Guanine^Cytosine)
that assemble into rings (rosettes), that then stack axially to form hollow tubes with controllable 3-4 nm
in diameter and lengths up to several microns. They are so versatile that they can be functionalized
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