Biomedical Engineering Reference
In-Depth Information
unstable and tends to separate into more than one phase in order to lower the system free energy. For
example, a polymer solution can separate into two phases: a polymer-rich phase and a polymer-lean
phase. After the solvent is removed, the polymer-rich phase solidifi es and the pores are formed.
105
Solid-liquid phase separation can be achieved by lowering the temperature to induce solvent crys-
tallization from a polymer solution. After the removal of the solvent crystals (sublimation or solvent
exchange), the space originally taken by the solvent crystals becomes pores.
106
Fabrication of scaf-
folds by freeze-drying and cryogel formation belongs to this category. The common shortcomings
of the fabrication technologies discussed in this section are the lack of precise control of the 3-D
pore architecture of the scaffolds and lack of with relative low pore interconnection. To tackle these
problems, computer-assisted design and manufacture CAD/CAM is being adopted.
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3.3.2.2
Computer-Assisted Design and Manufacture
Lack of pore interconnection will result in a poor a nd noneffi cient nutrients, gas, and waste exchange
within the scaffolds. The internal architecture and topography of the scaffold not only affect cell
attachment but also infl uence alignment, which can subsequently affect the organization of the
generated ECM. Precise design and manufacture of scaffolds have stimulated a rapid development
of solid free-form fabrication and rapid prototyping techniques for scaffold manufacture enabling
formation of scaffolds with a controlled internal architecture. CAD/CAM techniques offer the
advantage of producing well-controlled 3-D structure with regular micropattern for a range of bio-
materials. Scaffolds produced by such means can be customized both in microstructure and overall
size and shape for preparation of implants tailored to specifi c applications or even to individual
patients. These techniques can be performed by applying the action of heat, light, or adhesives.
107,108
Selective laser sintering (SLS) and fused deposition modeling (FMS) are heat-based fabrication
techniques.
109,110
These techniques involve the application of heat to fuse layers of material to each
other by raising the biopolymer above its glass transition temperature and applying pressure.
110 -112
In addition to heat-based fabrication, light can also be used to create polymer structures. Photo-
polymerization involves the use of light to initiate a chain reaction, resulting in the solidifi cation
of a liquid polymer solution. Stereolithography and photolithography are the photopolymerization
techniques that have been used in the fabrication of TE scaffolds.
113 -115
Another approach to fabricate scaffolds is to bind polymers by using solvents or adhesives rather
than heat or light, eliminating any biomaterial limitations such as heat compatibility or photoinitia-
tor dependence. An example of this type of fabrication is 3-D printing (3-DP) in which a binder
solution is deposited onto a biomaterial powder bed using an ink-jet printer. Three-dimensional
structures of approximately 200-500 μm are fabricated, one layer at a time.
116,117
Like 3-DP,
pressure-assisted microsyringe (PAM) fabrication also involves layer-by-layer deposition with the
solvent acting as a binding agent.
118,119
Manjubala et al.
120
used a rapid prototyping technique (3-D
printer) to produce scaffolds with chitosan and hydroxyapatites. The resulting scaffold has biomi-
metic mineral-organic composition and controlled macroporosity and reproducible microporous
internal architecture. Results from
in vitro
cell culture experiments indicate that the architecture
encourages cell growth from the periphery to the middle of the pores. Stevens et al.
34
have used a
replica printing method to transfer stamps onto porous hydroxyapatite scaffolds. This replica print-
ing is a simple and inexpensive method to control spatial distribution of cells, which promotes the
hierarchical organization. Fukuda et al.
121
have developed a layer-by-layer deposition method to
control micropatterned cell coculture. By the formation of electrostatic complexes, the surface can
be switched from a cell-deterrent to a cell-adhesive surface.
3.4 MONITORING SCAFFOLDS' ARCHITECTURE
Quality control and adjustment of the scaffold manufacturing process are essential to achieve high-
standard scaffolds. However, most scaffolds are made from highly crystalline polymers, which
inevitably result in their opaque appearance. The 3-D opaque structure prevents the observation
