Rapid prototyping in tissue engineering: challenges and potential

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Figure 2. structure produced using fused deposition modeling. Uniformly
interconnected square channels are obtained with a pattern setting of 08 or 908.
The scaffold structure is highly regular and reproducible. The portion of the
filament that spans across two supporting points is subjected to gravity-induced
deformation during the solidification phase. Therefore, the setting of the machine
parameters, as well as the material properties, must be precisely controlled to
ensure minimum filament deflection. Filaments are aligned orthogonally, with
grooves at the intersection point between consecutive layers. Cells on the scaffold
must span across these grooves to cellularize the entire structure.
advantage of being able to use a greater range of
materials. The enhancement is achieved by incorporating
more jetting nozzles into the system [29]. Support
structures can be built using water, which is nontoxic
and easy to remove. In the work by Zhuo et al. [30],
biomolecules in the form of bone morphogenic protein
were embedded in the bulk material and then released
slowly as the scaffold degraded.
PAM: A microsyringe is used to expel the dissolved
polymer under low and constant pressure to form the
desired pattern. The resolution of this method is on a
cellular scale, which is remarkably high compared with
the techniques described previously. Vozzi et al. [31]
developed PCL and PLLA scaffolds with line width of
20 mm. It has been demonstrated that the performance of
this method is comparable to that of soft lithography [33].
However, capillaries with a very small diameter require
careful handling to avoid any tip breakage. Higher
pressure is also needed to expel the material from a
small orifice.
Robocasting: This patented system is able to lay down
a highly concentrated, pseudoplastic-like colloidal suspension
[32]. Therriault et al. [34] fabricated a 3D microvascular
network by robocasting fugitive organic ink,
followed by scaffold infiltration with epoxy resin and
further postprocessing.
In general, the scaffolds fabricated using the melt or
solution deposition techniques described are usually
meant to serve as hard-tissue scaffolds. Landers and
Mülhaupt [35] have developed an aqueous system, the 3D
bioplotter, to meet the demand for fabrication of hydrogel
scaffolds useful in soft-tissue engineering. Hydrogels are
becoming increasingly popular as a material for tissue
engineering because of their high water content and the
fact that they have similar mechanical properties to those
of many soft tissues in the human body. Ang et al. [36]
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Review TRENDS in Biotechnology Vol.22 No.12 December 2004
adopted a similar concept to develop a robotic dispenser,
the rapid prototyping robotic dispensing system(RPBOD),
for the fabrication of a chitosan scaffold.
3D bioplotter: The key feature of this method is the
3D dispensing of liquids and pastes into a liquid medium
with matched density. The plotting material leaves the
nozzle and solidifies in the plotting medium after bonding
to the previous layer. The liquid medium compensates for
gravity and hence no support structure is needed.
Hydrogel scaffolds with well-defined internal pore
structure were prepared by Landers et al. [37]. The
hydrogel scaffolds had interconnected pores, 200–400 mm
in diameter. However, the hydrogel presented a smooth
surface, which might be nonadherent to cells [38]. Therefore,
further surface coating was required to render the
surface favorable for cell-adhesion. Fibroblasts seeded on
the scaffolds showed almost complete coverage of cells.
However, the scaffolds had limited resolution and mechanical
strength. Material rigidity was shown to influence
cell spreading and migration speed, as demonstrated by
Wong et al. [39]. Cells displayed a preference for stiffer
regions, and tended to migrate faster on surfaces with
lower compliance.
RPBOD: This system, developed by Ang et al. [36],
consists of a computer-guided desktop robot and a onecomponent
pneumatic dispenser. Material in liquid form
was dispensed into a dispensing medium through a small
Teflon-lined nozzle. Chitosan scaffolds with pore size of
400–1000 mm were produced in the preliminary study.
Particle-bonding techniques
In particle-bonding techniques, particles are selectively
bonded in a thin layer of powder material. The thin 2D
layers are bonded one upon another to form a complex 3D
solid object. During fabrication, the object is supported by
and embedded in unprocessed powder. Therefore, this
technique enables the fabrication of through channels and
overhanging features. After completion of all layers, the
object is removed from the bed of unbonded powder [20].
The powder utilized can be a pure powder or surfacecoated
powder, depending on the application of the scaffold.
It is possible to use a single one-component powder or a
mixture of different powders, blended together.
These techniques are capable of producing a porous
structure with controllable macroporosity as well as
microporosity. The microporosity arises from the space
between the individual granules of powder. These techniques
offer control over pore architecture by manipulating
the region of bonding. However, the pore size is limited
by the powder size of the stock material. Larger pores can
be generated by mixing porogen into the powder bed
before the bonding process.
The powder-based materials provide a rough surface to
the scaffold. It has been suggested that topographical cues
might have a significant effect upon cellular behavior [40].
As a cell attaches to the scaffold, stretch receptors are
activated. Receptors on the scaffold surface might be
subjected to varying degrees of deformation, leading to
activation of cell signal transduction pathways. Therefore,
scaffolds fabricated via a particle-bonding technique