Biomedical Engineering Reference
In-Depth Information
of stem cells can be controlled by mechanical forces [26, 27]. Extracellular matrix-
associated gene expression of more mature cells such as osteoblasts can be upregu-
lated using mechanical forces [28]. It is this concept of remote control of
mechanotransduction that has led to developments in the application of magnetic
microparticles and nanoparticles to tissue engineering.
Mechanical forces can be applied to cells that are seeded onto a 3-D scaffold in
a variety of ways. Such methods include shear forces induced from fl uid fl ow and
compressive/tensile forces applied directly to the cell-seeded scaffold (and thus
transmitted indirectly to the cells seeded onto the scaffold). There are various
limitations using these techniques, but these may be overcome by using magnetic
microparticles and nanoparticles as mechanotransducers.
By using magnetic particles to transmit force directly to the cells, the scaffold
geometry can be complex, whereas in compressive/tensile regimes the scaffold
must be of uniform dimensions in order to allow cell loading throughout the scaf-
fold. In addition, shear forces applied using fl uid fl ow through complex scaffold
structures vary greatly with little control. The technique also allows a controllable
level of force to be varied in different regions of the tissue- engineered construct,
simply by changing the magnetic fi eld geometry, the type of particle attached to
the cells in each region, or the number of particles attached to each cell in each
region.
In order to exploit this, a magnetic ion channel activation (MICA) bioreactor has
been designed specifi cally for tissue engineering purposes [29]. This system uses
permanent NdFeB magnet arrays to apply cyclical magnetic fi elds to cells (in either
2 - D or 3 - D confi guration) that have magnetic particles attached to the cell mem-
branes (Figure 8.2). In this way, forces in the order of a few piconewtons per
particle can be applied to each cell. These forces are suffi cient to activate the
mechanosensitive ion channels and, by targeting specifi c receptors on the cell
surface, it is possible to control the production of tissue matrix components. Short-
term experiments have demonstrated an upregulation of extracellular matrix
(ECM)-related gene expression for both cartilage and bone, while longer-term
Perfusion
Chamber
Magnet Array
Drive Sled
& Motor
Drive
Electronics
Connector
Block
Pump
Computer
Controller
Incubator
Reservoir
Figure 8.2
Schematic of the 3 - D magnetic ion channel
activation system housed inside an incubator.
