Biomedical Engineering Reference
In-Depth Information
to accelerate tissue growth and production is needed. Different research groups have devel-
oped different bioreactors [134]. They usually have been used to improve seeding efficiency,
proliferation, and osteoblast differentiation [8]. In these culture chambers the cells will grow,
proliferate, and differentiate to bone-forming cells, all in sterile conditions. These bioreactors
mainly fall into mechanical (compressive, rotatory, and spinning) and perfusion (running a
flow of fresh media over cells) categories in order to optimize the environment for osteoblast
growth and differentiation [135, 136]. The efficacy and problems with each type are under
investigation and it seems the perfusion systems show the best results for osteoblastic
differentiation and mineralized matrix deposition [137].
Bone bioreactors have been divided into three main groups.
1.
A spinner flask is the simplest type: cells on a three-dimensional scaffold are suspended
in a media container and stirred by about 50 rpm. The cell viability, proliferation, and
distribution compared to a static group are improved but the size of the produced tissue
is limited because by increasing the flow for increasing the tissue perfusion, especially for
deeper cells, generates a shear force, leading to necrotic damage in the surface cells [137].
2.
A rotating vessel (sometimes called the NASA bioreactor) is another type of rotational
reactor that usually employs horizontal rotation of solid, bubble free, vessels. In this
type of vessel the necrotic effect of shear stress is lessened. In one comparison between
these two methods and control, osteoblastic activity was increased by spinner flask
culture after 21 days due to superior media mixing [138, 139].
3.
The perfusion method is designed to mimic blood supply. In this method various types
of flow with different speeds, frequencies, and continuity (unidirectional, oscillating,
pulsating) can run the media over the growing cells and at the same time gas exchange
is provided by another pomp system. Frequency of flow, flow rate, and shear stress are
important variables for the perfusion system method [137, 140].
While it is premature perhaps to describe our nanoimpulse system as a bone bioreactor, it
is certainly simple, efficient, and scalable. However, it is currently better defined as an oste-
oblast bioreactor as it is two-dimensional. Our future work, however, will focus on building
this into a three-dimensional system for bone-tissue engineering.
Conclusions and Future Outlooks
Stem cells show a wide range of reactions to their nanoenvironment. These mechanotrans-
ductory reactions are likely largely due to changes in FA formation and concomitant intra-
cellular pathways activation. Nuclear responses and gene expressions could also be generated
by these nanoscale stimuli. Conduction of stem-cell fate with induction of mechanical stim-
ulation could introduce a new generation of bioreactors. To this end, we have introduced a
new nanoscale method of MSC stimulation for targeted osteoblastogenesis. This does not
rely on novel materials, complex chemistry, or electronic clean-room facilities. Rather, it is
based on traditional cell-culture plastics with simple addition of piezo ceramics. Upscaling
to bioreactors that can prime autologous MSCs to form osteoblasts without recourse to sol-
uble factors can be easily envisaged. It could also be envisaged that
in vitro
experiments
could be used to inform therapy (whole-body vibration) with the noted caveat that the mod-
eling from cell to whole body is nontrivial and much research aimed at practical/theoretical
scaling between nanoscale cell culture and the human body is required. Such techniques
could be complementary to existing external stimuli for musculoskeletal regeneration such
as extracorporeal shock wave treatment.
