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3D bioprinting for tissue engineering: Stem cells in hydrogels

(see Section 4.3).

4. Using Hydrogels for 3D Bioprinting

Hydrogels are an ideal tissue engineering material
which can be sourced naturally, created synthetically
or used in combination with other materials [61–64] . Hy-
drogel networks are comprised of polymer or peptide
chains. They have a high content of water, ideal for
absorbing high levels of nutrients and oxygen [65] , al-
lowing cells to migrate within the scaffold [66] and the
waste to diffuse out [67] .
Synthesised materials, such as those based on po-

lyethylene glycol and polyacrylamide, offer more
Figure 2. Mechanisms of degradation: bulk (A) and surface (B) control over modification than naturally derived mate-
degradation.
rials such as alginate, collagen, fibrin and hyaluronic
cellular response to the material. For example, during acid [62,64] .
bulk degradation scaffolds can become more porous,
which in turn will have a profound effect on cell mi- 4.1 Synthetic Materials
gration behaviour and nutrient uptake. Having control over gelation time and mechanical
When selecting a bioprintable material which has a strength are two of the most important elements in
suitable degradation profile, it is necessary to also hydrogel bioprinting. If the gelation time is too long,
consider whether the cells will contract the scaffold in the spatial resolution is lost and layers cannot be
any way and change its dimensions or whether the printed with accuracy. To control the setting time the
material’s swelling behaviour will be altered and the gelation mechanism can be manipulated by chemically
effect any by-products from degradation may have on modifying the material, introducing crosslinking
surrounding tissue. A relatively inert and printable agents or varying the polymer content [68] . Müller et
material or combination of materials that maintain the al. [69] were able to control the printability of Pluronic,
correct dimensions could still produce by-products a block-copolymer, by mixing acrylated with unmodi-
that are toxic or not readily removed by the body [55] fied Pluronic F127 and stabilising the structure
and therefore present new challenges in vivo. through ultraviolet (UV) crosslinking while Barry et
In order to assess the degradation behaviour of a al. [70] used direct-write assembly and UV photopoly-
material, factors such as chemical composition, ther- merisation to produce poly(acrylamide)-based gels for
mal properties, surface area to volume ratio and ste- fibroblast culture. With any of the techniques the
reochemistry must also be taken into consideration. process of printing a new layer should not disrupt or

3.4 Mechanical Strength and Structural Integrity dissolve the previously deposited material.
Hydrogels as a whole have a high water content
As stated in Section 2.3, maintaining structural integr- which is ideal for maintaining cell viability. However,
ity at the same rate as cell growth is highly challeng- the material provides low structural support [71] . By
ing but necessary. Not only does it provide cells with a using chemical or physical crosslinking methods this
physical support, studies have also shown that a me- can also be improved and therefore solve two major
chanical strength which matches in vivo conditions issues using one modification technique. Being able to
can strongly influence cell proliferation and differen- control scaffold formation in this way would suggest
tiation [56–58] . Several researchers have used a hybrid that for bioprinting, synthetic materials, owing to their
material approach to create a mechanically suitable customisability, are superior to naturally-derived ma-
environment [59,60] . However, the printability, from cha- terials. However, cellular interactions and biocompa-
nges in viscosities and a mismatch in the most suitable tibility are almost always better on natural materials
printing technique for the materials, must be assessed than synthetic [72] . To improve the biocompatibility of
and thus further adds to the complexity of the issue. synthetic materials, functional sequences, such as pep-
These problems are not insurmountable and several tide adhesion motifs, can be covalently attached to the
researchers have created 3D printed hybrid scaffolds material. The drawback of this approach is introducing

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