Biomedical Engineering Reference
In-Depth Information
3.5 CONTROL AND MONITORING OF SCAFFOLD ARCHITECTURE
FOR TISSUE ENGINEERING—A CASE STUDY
The clinical application of 3-D-engineered constructs with specifi c dimensions and architecture
will most certainly rely on the development of computer-assisted techniques to manufacture the
appropriate scaffolds for individual cases. Unfortunately, that achievement is still some steps ahead
of what the actual state of the art in TE can provide. As it has been pointed out in this chapter, a
great deal of research involving the response of cells to several stimuli in a 3-D dynamic environ-
ment needs to be done before that stage can be reached. Despite the array of highly controlled and
reproducible morphological features that computer-assisted manufacturing techniques can offer,
the implementation of these methods on the average TE laboratory is not realistic. In addition to a
relatively high cost of operation, most of them are extremely time consuming and cannot generate
the amount of scaffolds usually required for most biological studies in a practical timescale. In this
section, we discuss the new manufacturing techniques developed by the authors' research group.
These techniques enable alteration of scaffolds' architecture in terms of pore shapes and intercon-
nectivity based on routine laboratory facilities. μ-CT and OCT have been explored to monitor the
scaffolds' architecture in a nondestructive manner. In the case of OCT, this has been achieved under
sterile conditions, which generates a new tool that sets in motion the online investigation of scaffold
degradation and tissue turnover.
3.5.1 D
EVELOPMENT
OF
N
EW
T
ECHNIQUES
TO
T
AILOR
S
CAFFOLD
A
RCHITECTURE
The exploration of new scaffold manufacture techniques with high productivity, easy operation, and
accurate control of scaffolds' architecture will be of great benefi t for the TE research fi eld since
a large number of scaffolds are frequently required for comparison or optimization of the culture
conditions in TE experiments. In the following sections, we present three techniques developed for
the manufacture of scaffolds, with advantages over existing methods.
3.5.1.1
Controlling Pore Interconnectivity in Porous PLLA Scaffolds by Dual Porogen
Traditional solvent-evaporation and salt-leaching technique makes use of a single porogen, usually
sodium chloride, to give rise to scaffolds with controllable porosity but poor pore interconnectiv-
ity.
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This characteristic renders them improper to tissue culture because it reduces the diffusion
of nutrients, gases, and metabolites across the scaffolds and impairs cell-to-cell contact. Based on
this technique, we have developed a new approach to increase pore interconnectivity.
146
In this new
approach, a dual porogen system is used: the water-soluble porogen, sodium chloride, creating mac-
roporosity and the water-nonsoluble porogen, naphthalene, producing pore interconnections. The
principle is illustrated in Figure 3.3.
NaCl LEACHING
WITH WATER
NAPHTHALENE
SUBLIMATION/
DISSOLUTION IN
THF
PLLA
SCAFFOLD
PLLA
Naphthalene
Pore
NaCl
Pore
PLLA
PLLA
Micropore
Naphthalene
FIGURE 3.3
Schematic diagram showing the principle of solvent evaporation/particulate leaching with
dual-porogen method. In this method, the NaCl crystals create the macroporosity, whereas the particles of
naphthalene generate pore interconnections.
