Biomedical Engineering Reference
In-Depth Information
particles can be very useful for more acute animal and cell studies providing a number of advan-
tages for preclinical investigations. For example, the electron dense, magnetic metal core can be
useful as a contrast agent to identify and track particles in vitro by electron microscopy and in vivo
by magnetic resonance imaging (MRI). Additionally, magnetic cores have been found to be useful
agents in both immunomagnetic isolation systems when combined with antibody conjugates as
demonstrated with microspheres
[19]
and even for cell targeting using magnetic fields
[20]
.
Another key advantage of the sol
gel and template methods for biomedical applications is the
ability to incorporate dyes into the silica during synthesis
[21]
providing visualization and tracking
capabilities. Fluorescent dyes have been used extensively for tracking nanoparticles in biological
assays
[22
26]
and for in vivo pharmacokinetic studies
[27]
. When combined with a metal core,
the resulting core-shell nanoparticles may be multifunctional containing magnetic (metal core) and
fluorescent of luminescent (doped shell) properties. Another potential application is the incorpo-
ration of biologically active compounds, such as antimicrobials or fluoride. MSNs are candidate
silica-based particles that are being investigated for such a purpose. Although few actual therapeu-
tic successes have been reported in dentistry to date, some in vitro studies have reported success in
delivering antibacterial compounds such as nitric oxide (discussed in 4.5.2.2).
4.4
Physicochemical properties of silica-based nanomaterials
Three important physical attributes of silica nanomaterials are size, shape, and surface functionali-
zation. The ability to control these three properties results in a wide variety of potential silica-based
nanomaterials and almost infinite number of physicochemical responses.
4.4.1
Size
Relevant to biomedical applications, the most attractive size range of silica materials appears to be
in the range of 10
1000 nm. Although applications vary, one goal is to reproducibly synthesize
particles within a narrow size range and the synthesis method has a strong influence on size distri-
bution. The size of silica-based nanomaterials can be relatively easily controlled over a wide range
spanning nanometer to micrometer. Both the sol
gel and template-assisted methods have good size
controllability and reproducibility, whereas the pyrolysis (fumed silica) is less controllable. Factors
that will influence size during synthesis include silica sources such as tetramethyl orthosilicate
(TMOS), tetraethyl orthosilicate (TEOS), and sodium silicate, acidic or basic catalysts, temperature,
solvents, and surfactant. Using the template method, size can be controlled by adjusting the
amounts of surfactants, including polymers, or the ratio of water-to-surfactant or organic solvent.
The surfactant forms a micelle (or inverse micelle) similar to a nanosized cavity (
Figure 4.3
). The
silica deposition occurs based on the micelles' size and keeps the spherical shape. When using
the sol
gel process, increasing the concentration of the silica source and catalyst will increase the
silica's size in a linear manner (
Figure 4.4
).
Nanoparticle size is extremely important for a number of reasons. Specific materials when
synthesized at the nanosize often possess different properties to those of the bulk or macroform
because of increased surface area. In regard to dental application, the size of the particle may influ-
ence the density that can be achieved in composite resins ultimately influencing mechanical and
