Biomedical Engineering Reference
In-Depth Information
of cell size. Thus topography is local, whereas geometry is global. Geometry is easier to control and
design using RP whereas topography is harder to defi ne and is a dynamic feature in tissue engineering
because cells will remodel a substrate.
It has been amply demonstrated that cells react to the topography of their substrate on which
they are seeded [7]. Furthermore it is important to note that characteristic topographical dimen-
sions may vary signifi cantly from one cell type to another. In addition, the adhesion and motility
of cells may be enhanced by their contact with a surface with topological features. It has also
been shown that the dimensions and aspect ratios of structures can affect the reaction of cells
to a marked extent, but despite several studies, we are still far from a full understanding of the
events involved [8]. However, much effort is being directed toward the study of the phenomena
that guide cell reaction to the geometry of the substrate on which they are seeded, and also the
reason why some cell functions are either enhanced or suppressed according to the spatial pat-
terns or geometry [9]. The scaffold-based tissue engineering is founded on the principle that
the microstructural environment of a cell undoubtedly conditions its behavior. However, there
are no hard-and-fast rules as to which type of geometry or topography is most suitable for this
process, and as mentioned in Section 4.2, there are no algorithms or rules to defi ne soft-tissue
microarchitecture.
At present there is no RP method, which enables scaffolds with a precision of less than a few
microns to be fabricated, and it is likely that smaller features would necessitate elimination of the
term rapid, since time is sacrifi ced at the expense of resolution. We can defi ne the resolution/time
of manufacture ratio (RTM ratio) as the maximum resolution (expressed as the inverse of minimum
feature length,
d
) divided by the time (
t
) required to realize a unit volume (
V
) of scaffold. The RTM
ratio is then
1/
d
____
RTM
=
t
/
V
and has been quantifi ed where possible in Table 4.1. The higher this number is, the more effi cient is
the RP method, and the better it lends itself to a high throughput scaffold production. Here we have
only used the manufacture time without considering solvent extraction, sterilization, cell seeding,
and proliferation times since these times will vary greatly with the selected application.
RP methods can also be characterized in terms of their fi delity, that is, the match between
structural features of the scaffolds and the actual CAD design. Obviously no technique has 100%
fi delity; in particular, methods that involve melting, swelling, or the use of solvents will show devia-
tions from the input design where usually the scaffold features are larger and less defi ned than the
specifi ed features.
In our experience, the optimum resolution for RP is the order of cell dimensions, or a few tens
of microns [10]. In most tissues the functional element is only a few cell diameters [11], so any
architectural dimensions greater than this diameter would probably comprise spatial control of cell
organization, which is the underlying philosophy behind scaffold-based tissue engineering.
4.5 FLUID-BASED RP MICROFABRICATION
Fluid-based RP methods use a solution or melt of polymer, which is extruded through a syringe
mounted on an arm or on the
z
-axis of a 3-D micropositioner. The material of the upper layer is
bonded to that of the lower layer in order to obtain a 3-D scaffold. Often an intermediate support-
ing layer is required to avoid collapse of the structure during fabrication, which is then sacrifi ced
in the postprocessing phase.
This group includes all the PAM-like methods, FDM and its variants, fi ber spinning, and dif-
ferent types of ink-jet-based organ printing. The resolution is generally a function of the viscosity
of the polymeric solution extruded as well as the diameter of the deposition head.
