Rapid prototyping in tissue engineering: challenges and potential

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Review TRENDS in Biotechnology Vol.22 No.12 December 2004
Consequently, researchers try to modify the conventional
techniques to overcome these inherent process
limitations. Kim and Mooney [13] produced polyglycolic
acid (PGA) fibers bonded with poly-L-lactide (PLLA) to
enhance the mechanical strength and the degradation
rate of the unbonded PGA fiber meshes. As a variant to the
freeze-drying process, Ho et al. [14] prepared scaffolds
using a freeze-extraction method, which was relatively
more time- and energy efficient. Murphy et al. [15]
enhanced pore interconnectivity by fusing the porogen
together to form a template, instead of using unbounded
particles in so1vent casting/particulate leaching process.
The result showed that holes were formed in pore walls,
guaranteeing pore interconnectivity. Chen and Ma [16]
created nanofibrous PLLA scaffolds which incorporated
interconnected spherical macropores. The macropores
were voids left by paraffin spheres, which were thermally
bonded before the casting of the polymer solution. In place
of paraffin spheres, Gross and Rodríguez-Lorenzo [17]
used a sintered salt template to produce PLLA-reinforced
apatite scaffolds.
Notwithstanding the improvements that have been
attained, the control over scaffold architecture using these
conventional techniques is highly process dependent
rather than design dependent. As a result, RP is seen to
be a viable alternative for achieving extensive and
detailed control over scaffold architecture [18,19].
Advanced scaffold-fabrication methods
RP is a common name for a group of techniques that can
generate a physical model directly from computer-aided
design data. It is an additive process in which each part is
constructed in a layer-by-layer manner. Table 1 presents
and compares the RP techniques that can be used to
fabricate scaffolds directly or indirectly.
Direct RP fabrication method
RP systems such as fused deposition modeling (FDM), 3D
printinge (3-DP) and selective laser sintering (SLS) have
been shown to be feasible for producing porous structures
for use in tissue engineering. In this review, the tissue
scaffold fabrication techniques are categorized by virtue of
their mode of assembly into one of two processes: the melt–
dissolution deposition technique and the particle bonding
technique.
Melt–dissolution deposition technique
In a typical melt–dissolution deposition system, each layer
is created by extrusion of a strand of material through an
orifice while it moves across the plane of the layer crosssection.
The material cools, solidifying itself and fixing to
the previous layer [20]. Successive layer formation, one
atop another, forms a complex 3D solid object.
Porosity in the horizontal XY plane is created by
controlling the spacing between adjacent filaments
(Figure 2). The vertical Z gap is formed by depositing the
subsequent layer of filaments at an angle with respect to
the previous layer. Repetitive pattern drawing will
produce a porous structure ready to be used as a scaffold.
A representative system using melt–dissolution
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deposition is FDM. This method spins off several new
systems that operate under similar principles.
FDM: In this method, a filament of a suitable material
is fed and melted inside a heated liquefier before being
extruded through a nozzle. The system operates in a
temperature-controlled environment to maintain sufficient
fusion energy between each layer.
Researchers have demonstrated the feasibility of
utilizing FDM to fabricate a functional scaffold directly.
Zein et al. [21] fabricated polycaprolactone (PCL) scaffolds
with a honeycomb structure and a channel size of 160–
770 mm. Samar et al. [22] have successfully produced a
polymer-ceramic composite scaffold made of polypropylene-tricalcium
phosphate (PP-TCP). The scaffolds were
reported to have a pore size of 160 mm and a mechanical
strength of 12.7 MPa, which is comparable to the tensile
strength of natural cancellous bone, which has a value of
7.4MPa [23]. In a recent study, human mesenchymal
progenitor cells were seeded on PCL and PCL-hydroxyapatite
(HA) scaffolds fabricated by FDM [24]. Proliferation
of cells toward and onto the scaffold surfaces was detected.
Drawbacks of the FDM technique include the need for
input material of a specific diametric size and material
properties to feed through the rollers and nozzle. Any
changes in the properties of the material require effort to
recalibrate the setting of the feeding parameters. As a
result, FDM has a narrow processing window. The
resolution of FDM is relatively low, at 250 mm. In FDM,
a limited range of material s can be used, with almost
complete exclusion of natural polymers, as the material
used must be made into filaments and melted into a semiliquid
phase before extrusion. The operating temperature
of the system is too high to incorporate biomolecules into
the scaffold, hence limiting the biomimetic aspects of the
scaffold produced. Moreover, the material deposited
solidifies into dense filaments, blocking the formation of
microporosity. Microporosity is an important factor in
encouraging neovascularization and cell attachment [25].
Modifications of FDM to circumvent these limitations
have encouraged the emergence of several new techniques.
These include techniques that eliminate the
requirement of precursor filaments or a system with
reduced operating temperatures. Some variants of the
FDM process include the 3D fiber-deposition technique
[26], precision extruding deposition (PED) [27] and precise
extrusion manufacturing (PEM) [28].
3D fiber-deposition technique: In this method, the
feedstock material is in a pellet or granule form that can
be poured into the heated liquefier directly. Poly(ethylene
glycol)-terephthalate-poly(butylenes terephthalate)
(PEGT–PBT) block copolymer scaffolds have been
fabricated for articulate tissue engineering applications
[26]. Material flow is regulated by applying
pressure to the syringe.
PED: The extruder in this system is equipped with a
built-in heating unit to melt the feedstock material, hence
eliminating the need to produce precursor filaments. PCL
scaffolds with a pore size of 250 mm were fabricated [27].
PEM: PLLA scaffolds with controllable porous
architectures from 200 to 500 mm in size have been
produced [28].