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Smart hydrogels for 3D bioprinting

Like the electric field responsive hydrogel, there
hasn’t been a direct application of magnetic respon-
sive hydrogel as a bioprintable ink. 3D printing tech-
niques might be utilized as MNP dispenser instead of
blending. Moreover, it might as well need blending
with ECM proteins for better cell attachment.

5. Potential and Future Outlook
Figure 3. Electroactuation scheme. The rod-shaped pluronic
hydrogel is placed between two electrodes (A) with or (B) 5.1 Computational and Dynamic Modeling of
without an applied electric field. (adapted from [84] )
Cell-hydrogel
4.5 Magnetic Hydrogels Hydrogel in bioprinting acts as a matrix that supports
and regulates the cells encapsulated inside the matrix.
Magnetic hydrogels are a combination of hydrogel At the current stage, computational models have been
systems with magnetic nanoparticles (MNP). MNPs set up to assess hydrogel contraction and deformation
such as cobalt ferrite (CoFe 2O 4), iron platinum (FePt), due to cellular events such as migration, proliferation
iron (III) oxide (Fe 2O 3) and iron (II, III) oxide (Fe 3O 4) and traction, cellular concentration and distri-
respond to magnetic field, resulting in hydrogel de- bution [98,99] . These models demonstrate the interaction
formation [91] . As shown in Figure 4, magnetic hydro- between cells and materials, and quantify and corre-
gels can be fabricated through simple blending, or in late cellular events with engineered microenviron-
situ precipitation, or grafting-onto method. Blending ments [100] .
method is easy to use and could be incorporated di- The ability of smart hydrogels reacting to a stimu-
rectly with bioprinting techniques. However, uniform lus will also create an impact on the cells encapsulated
distribution of MNPs remains a major issue. In situ inside the hydrogel. In a smart hydrogel, when the
precipitation method ensures a uniform dispersion of hydrogel’s properties change with time, time is an
MNPs, but this method is limited by the harsh alkali additional factor needed to understand the dynamic
treatment during the process. Through grafting-onto cell-material interaction. In a proposed model demon-
method, MNPs can be covalently bonded to the hy- strated by Satoru et al., epithelial growth was more
drogel system. Therefore, it has advantages such as a aptly simulated when timescale of tissue deformation
steady dispersion of MNPs over a certain time period. was accounted for as opposed to modelling at a
However, this method requires MNP binding site in quasi-static state [39] . This demonstrates the need to
the hydrogel polymer. Therefore, natural polymers are consider dynamic changes in substrate viscoelasticity
not suitable for this method or require further modifi- properties when determining tissue morphogenesis. In
cation [92–96] . the case of smart hydrogel, the changes in properties
of smart hydrogel will affect the maturation of engi-
neered tissue and this remains an area for future inves-
tigation.

5.2 Development of New Hydrogel Characteriza-
tion Techniques

The rheological properties of the hydrogel such as
viscosity, viscoelasticity, shear-thinning, or shear-
thickening behaviors must be well-characterized for
the different stages of bioprinting process, including
before, during, and after the 3D printing process.
Hence, there is a need to develop new characterization

techniques to measure these behaviors at the specific
Figure 4. Magnetic hydrogel preparation methods: (A) blend- time points.
ing method, (B) in situ precipitation method and (C) the graft- Traditional extensiometry and compression tests
ing-onto method. Adapted from [97] . have been employed to characterize mechanical prop-

8 International Journal of Bioprinting (2015)–Volume 1, Issue 1