Rapid prototyping in tissue engineering: challenges and potential

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algorithm can be interfaced with various RP technologies,
to achieve automated production of scaffolds.
Because RP processes offer complete user control in
terms of the structural features of the scaffold, it is
therefore possible to characterize the scaffold using an
automated algorithm. A computer-aided characterization
approach can be applied to predict the effective mechanical
properties of scaffolds and also to investigate the effect
of design and process parameters on the structural
properties of the scaffolds. Fang et al. [73] characterized
the effective mechanical properties of porous PCL scaffolds
manufactured by PED using a computational algorithm
for finite element implementation and numerical solution
of asymptotic homogenization theory.
The ease of scaffold fabrication using RP provides a
straightforward way to study the cell–matrix interaction.
The effects of material rigidity, surface topography and
roughness, pore size and architecture can be investigated
independently to gain more insight into cell behavior.
Recent studies have displayed a new school of thought,
using the concept of layered manufacturing techniques to
produce an organ directly. These new technologies include
organ printing [74–76], laser printing of cells [77],
photopatterning of hydrogel [78] and microfluidics technology
[79].
Organ printing: Boland et al. [76] developed a cell
printer to implement the technology. The device is capable
of printing single cells, cell aggregates and the supportive
thermoreversible gel that serves as ‘printing paper’. These
authors demonstrated the feasibility of this technique by
printing a tubular collagen gel with bovine aortal
endothelial cells.
Laser printing of cells: A laser-based printer, termed
matrix-assisted pulsed laser evaporation direct write
(MAPLE DW), was used to deposit micron-scale patterns
of pluripotent embryonic carcinoma cells onto thin layers
of hydrogel [77]. A cell viability of 95% was reported.
Photopatterning of hydrogels: Valerie and Sangeeta
[78] adapted photolithographic techniques from the silicon
chip industry. The process starts with filling a Teflon base
with a thin layer of polymer solution loaded with cells. UV
light is shone through a patterned template atop the thin
film, curing the exposed polymer that sets with cells
inside. Complex 3D structures, containing regions of
different cells, can be built by using different templates
and adding layers atop each other.
Microfluidics technology: Tan and Desai [79]
reported a layer-by-layer microfluidic method to build a
3D heterogeneous multiplayer tissue-like structure inside
microchannels. This approach extends the 2D cell patterning
technique into the vertical axis, involving immobilization
of a cell–matrix assembly, cell–matrix
contraction and pressure-driven microfluidic delivery
processes.
Conclusion
The emergence of various different approaches in tissue
engineering, ranging from a scaffold-based approach to
scaffold-free layer-by-layer manufacturing technique, has
highlighted the fact that the field of tissue engineering is
still growing. Looking towards the future, RP technologies
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Review TRENDS in Biotechnology Vol.22 No.12 December 2004
hold great potential in the context of scaffold fabrication.
This technology enables the tissue engineer to have full
control over the design, fabrication and modeling of the
scaffold being constructed, providing a systematic learning
channel for investigating cell–matrix interactions.
Additionally, indirect RP methods, coupled with conventional
pore-forming techniques, further expand the range
of materials that can be used in tissue engineering.
Inspired by the additive nature of layered manufacturing,
the layer-by-layer fabrication method underlines the
future development of tissue engineering. Further development
and advances in RP in tissue engineering require
the design of new materials, optimal scaffold design and
the input of enhanced knowledge of cell physiology,
including optimal cell seeding and vascularization, so as
to enable the tissue engineer to lay down more specific
design requirements. Nevertheless, RP is a promising
candidate, serving as a methodical interface between
tissue and engineering.
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