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Nazia Mehrban, Gui Zhen Teoh and Martin Anthony Birchall

In this review we introduce some of the materials acoustic radiation field and form droplets from an
used for bioprinting, how stem cells are currently in- air-liquid interface. Control of droplet size and rate of
corporated into the materials and the advantages and deposition comes from ultrasound pulse, duration and
limitations of the techniques used to achieve this. Here amplitude [18] . The acoustic methods can be modified
the focus is to review 3D bioprinting techniques cur- so that they are not reliant on nozzles [19] . This reduces
rently employed to create implantable tissue. However, the risk of clogging and shear stress on cells. There
the same techniques may also be employed to create are also no changes in temperature during droplet
models for studying 3D cell behaviour, diseases and formation. However, there is a risk of causing cell
modes of repair. lysis and membrane damage from the frequencies
used to change the piezoelectric crystal shape.
2. Techniques for 3D Bioprinting One of the main drawbacks of using either thermal
or piezoelectric-based inkjet printing methods is that
The main approaches to 3D bioprinting are: biomimi-
cry (taking inspiration from nature to develop novel only liquids with low viscosities are easily printable.
materials), autonomous self-assembly (using cellular This introduces further problems in creating a solid
organisation to guide the development of bioprinted structure once the bioink has been deposited onto the
[20]
tissues) and mini-tissue building blocks (identifying stage . Methods of addressing this issue are outlined
and recreating the building blocks of tissues to pro- in Section 3. Similarly, only low cell numbers can be
printed to avoid the nozzle from clogging and to re-
duce complex systems) [13] . For any one of these strat- duce shear stress on the cells [13] . However, once these
egies, there are a number of techniques that can be issues are addressed, inkjet methods offer fast, cheap
employed for their fabrication.
and high resolution bioprinting with the ability to
2.1 Inkjet Bioprinting change drop size and density, thereby the ability to
create gradients. When this is coupled with multiple
Based on 2D ink-printing technology, inkjet printing is nozzles, it is clear why inkjet printing techniques are
still the most popular printing method for 3D biologi- so attractive to tissue engineers [21,22] .
cal tissues analogues. The first modifications of the
technology replaced the ink reservoir with bioink and 2.2 Laser-Induced Forward Transfer Bioprinting
the paper-feed tray with an x-y-z controllable stage [14] . (LIFT)
Inkjet printers use thermal or acoustic methods to de- Laser-induced forward transfer (LIFT) technology
liver controlled volumes of the bioink to previously uses pulses of laser focused on a ‘ribbon’ upon which
defined locations [15] and build the structure layer-by- the biological material is layered as a solution. The
layer. Thermal methods generate heat at the print head pulse creates a high-pressure bubble which forces the
which forces ink out of the nozzle through pressure biological material off the ribbon and onto a collector.
pulses. Although temperatures can reach 200–300°C The technology is not as popular as inkjet and micro-
during thermal inkjet printing, this lasts a few micro- extrusion for bioprinting but is increasingly being
seconds, resulting in an overall temperature rise of used [23,24] . The component set-up for LIFT is entirely
4–10°C for aqueous systems, which has been shown different to inkjet and microextrusion technologies
not to have a detrimental effect on cell viability [16] . and as such the printing resolution and speed is de-
This method of printing is fast, cheap and readily pendent on factors including laser energy, material
available. However, although temperature effects on wettability and surface tension, the spacing between
cells has been shown to be minimal, other factors such the ribbon and the substrate and material viscosity [25] .
as print-head clogging, mechanical stress and unrelia- The benefits of LIFT are that it is a nozzleless sys-
bility in bioink dispensing, present the biggest disad- tem and so clogging of the print head is no longer an
vantages. issue, a range of viscosities can be printed without
Acoustic inkjet printing technology is based on ge- causing a detrimental effect on cell viability [26] and
nerating pressure in the nozzle by applying a voltage high cell numbers can be printed [27] . These are all ad-
to a piezoelectric crystal which changes the crystal’s vantageous over conventional bioprinting systems.
conformation. Controlling this process precisely al- However, the complexity of LIFT is its biggest
lows the bioink to be deposited as droplets [17] . A mod- downfall. Individual ribbons are required for deposit-
ification of this process uses ultrasound to create an ing different bioinks which can be time-consuming

International Journal of Bioprinting (2016)–Volume 2, Issue 1 7