Biomedical Engineering Reference
In-Depth Information
tissue
in vitro
by using SFF systems. The concept of organ printing by Mironov et al.
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and robot-
assisted construct fabrication aims at making this dream a reality.
2.4.2 C
ELL
/O
RGAN
P
RINTING
With the advantages of being inexpensive as well as high throughput, commercial thermal ink-jet
printers have been modifi ed to print biomolecules onto target substrates with little or no reduction
of their bioactivities, resulting in the creation of DNA chips, protein arrays, and cell patterns. Most
recently, by means of computer-assisted deposition, viable cells can be delivered to precise target
positions within a matrix. Furthermore, using different cell types in combination with different
hydrogels (bio-inks), which are then delivered to exact positions to mimic tissue structures of the
original tissue, can be envisioned by using multiple nozzles. Thus, the printing of dissociated or
aggregated cells based on specifi c patterns, and their subsequent fusion, may allow the development
of replacement tissue or even whole organ substitutes.
Several groups have demonstrated the ability to extrude biopolymer solutions and living cells
for 3-D tissue engineering applications. Sodium alginate solutions were deposited into calcium
chloride solution using 3-D dispensing nozzles to produce a hydrogel TEC. Boland's group
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proved the ability to print viable cells either by direct-writing or the ink-jet printing method. Since
the physiological properties of mammalian cells strongly depend on the culture conditions and they
are very sensitive to heat and mechanical stress, there was a major concern that the cells could be
damaged or lysed by the conditions present during thermal printing. The temperature in the nozzle
of the cartridge can be 300°C or higher. The study by Boland et al. indicates, however, that cells
can be delivered successfully by using a modifi ed ink-jet Hewlett-Packard (HP) printer, and most
of these cells (
90%) were not lysed during printing. The HP ink-jet printer technology is based on
vaporizing a micrometer-sized layer of liquid in contact with a thin-fi lm resistor. As the timescales
involved in the drop ejection process are small, there is not enough time for heat to diffuse into the
bulk liquid. While the surface in contact with the liquid can peak at 250-350°C, the bulk liquid
does not rise more than a couple (approximately 4-10°C) degrees above ambient. This situation
could change, however, depending on the liquid and thermophysical properties of the ink. Although
mammalian cells are more sensitive to high heat and strong mechanical stress than bacteria, their
volume is also relatively small compared to the total volume of the printed droplet. The fact that
these mammalian cells are viable, can proliferate, and differentiate indicates that damage from the
heat and mechanical stress during the very short timescale of printing is avoided. Moreover, the
3
>
phosphate buffered saline (PBS) used for the cell print suspensions could have caused a further
decrease in cell volume, because they are expected to shrink by osmosis in this hypertonic solu-
tion, effectively preventing clogging of the nozzle during printing. While these initial studies were
mainly concerned with the survivability of cells, future studies will need to optimize the ink-jet
technology along with the hydrogels to be successfully used in the fi eld of tissue engineering.
Future studies will aim at modifying current ink-jet printers based on piezoelectric tech-
nology for possible use in cell printing.
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However, there are some challenges in adapting com-
mercial piezoprinters for organ printing. Commercial piezoprinters use a more viscous ink, and
hence minimizing ink leakage and preventing formation of vapor is diffi cult. More viscous inks
help to eliminate the need for complex fl uid gates between the ink cartridge and print head to
prevent the ink from backfl ow. However, this technique comes at the expense of requiring more
power and higher vibration frequencies, both of which can break and damage the cell membranes.
Typical commercial piezoprinters use frequencies up to 30 kHz and power sources ranging from
12 to 100 W. These frequencies create a problem because vibrating frequencies ranging from 15 to
25 kHz and power sources from 10 to 375 W are often used to disrupt cell membranes. Adapting
piezoprinters for less viscous ink to lower the frequency and power would be challenging, since
ink leakage and mist formation during printing could obscure the pattern. Future studies need to
overcome these problems.
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