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3D bioprinting for tissue engineering: Stem cells in hydrogels

and expensive when printing multiple materials or cell through which cells are deposited as spheroids without
types. Furthermore, the ribbon coating method does a secondary support material [38] . Microextrusion prin-
not lend itself to distributing cells accurately and met- ting has already been used to produce aortic valves [39]
al contaminants are present in the final printed con- and pharmokinetic [40] and disease [41] models. Further-
struct; as metal coating is used to create a laser energy more, there is room for improvement as the technolo-
absorbing layer on the ribbon. gy is capable of printing non-biological materials at
Even so, as the price for 3D printing is decreasing high resolution.
and LIFT technology is becoming more accessible,
several researchers have used it to fabricate clinically 2.4 Stereolithography and Projection Pattern Bio-
relevant constructs, both acellular [28] and cellular [29,30] . printing
As component parts are modified to suit bioprinting Stereolithography is traditionally used to fabricate solid
for the purpose of tissue engineering, the interest in structures from photocurable polymer or resin using a
this technology is likely to grow substantially. laser and an x-y-z-controlled stage [42] . The technique is
2.3 Microextrusion Bioprinting based on solid freeform fabrication with polymerised
layers printed bottom-up, although top- down stereo-
Microextrusion printing is one of the most popular lithography approaches also exist. The printing resolu-
and cheapest methods of non-biological printing [31] . tion is dependent on laser energy and focus. Although
The technique uses force to extrude material via a mi- traditionally the technique has been used to produce
croextrusion head onto a stage, both of which can acellular scaffolds, researchers have incorporated pho-
usually be controlled along the x, y and z axes [32] . For topolymerisable proteins and cell-guiding cues into
bioprinting, materials can be extruded mechanically or the scaffolds using stereolithography [43] .
pneumatically [33] . Pneumatic systems are ideal for Projection stereolithography, also known as digital
printing materials that have higher viscosities [34] as micromirror device microfabrication, is a modification
they are limited only by the system’s air-pressure ca- of the original system which uses micromirrors to
pabilities and nozzle diameter. The mechanism is sim- create a reflective photomask for fabricating the scaf-
ple but delays caused by the compressed gas which fold layer by layer [44] . Further advancements in the
controls material flow can affect the printing resolu- technology have led to the development of a more
tion. Mechanical motor-based microextruders are more complex system which allows the entire 3D structure
complex and provide better spatial resolution but are to be polymerised at the same time [45] . Such a system
limited by the forces they can generate and therefore can dramatically reduce the printing speed.
struggle to extrude materials with high viscosities [35] . The main drawback with using traditional stereoli-
The temperature of the stage and print head of a thography to print scaffolds is that it is not easy to
microextrusion system can be controlled, which al- incorporate cells into the structure and maintain via-
lows a range of materials to be printed [13] . Further- bility as it is being fabricated, unless the set-up is
[46]
more, as force is used to extrude the material, high cell modified first . Typically the scaffold is formed first
densities can be printed, although, as with inkjet me- and cells are seeded post-fabrication.
thods, the forces generated can affect cell viability. As 3. Selecting Suitable Materials for 3D Bio-
microextrusion uses higher forces than inkjet printing printing
methods, the cell viability can be as low as 40% [36] or
even lower if higher pressures are used. This impact The main challenge in engineering tissues is replicat-
on cell viability can be reduced by lowering the extru- ing the in vivo environment chemically, mechanically
sion pressure and printing through nozzles with a large and morphologically. Therefore, the scaffold material
gauge size, although this in turn affects the printing on which the cells will be cultured is one of the most
resolution and speed. Nevertheless as microextrusion important initial choices to be made. The source of
technology can print high cell densities and can be these materials may be natural or synthetic (Figure 1).
fitted with multiple extrusion heads, allowing for mul- Both types of materials have been used for tissue eng-
ti-material or multi-cell printing [37] , it remains the ineering in equal measure [47−49] . Natural materials are
most popular method for self-assembly cell printing; biocompatible while synthetic materials can be modified

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