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Liu, et al.
that the required part can be left. Second, MPC polymer, need to have the following characteristics: bioinks should
the hard-to-attach layer, is covered first. The metal part protect cells from extrusion, inappropriate environments,
is washed off then. Thus, the adhesion layer can stay on and other damages in the fabricating processes ; they
[45]
the surface of the core layer to allow the cells to attach. should have suitable mechanical properties, such as
Finally, to make the microplate fall off from the substrate, high mechanical integrity, viscoelasticity, and stability;
the sacrificial layer is washed away, and the standardized they should consider the biocompatibility, such as
cell-attached microplates can be obtained. Different from non-toxicity, and non-immunogenicity, and also cell
the cells that adhere to the surfaces of the microplates, adhesion promotion properties; and they should also own
cells can also be maintained inside 2D structures. As other necessary characteristics including printability,
shown in Figure 2C, mixing cells with photo-cross- insolubility in the culture medium, commercial feasibility,
linkable resin (PEGDA, polyethylene glycol diacrylate), and manufacturing efficiency.
and ring-shaped (arbitrary shape is available) cellular Researchers such as Saito et al., Jia et al., and Mobaraki
modules can be fabricated by exposing the resin inside et al. have made a summary of the materials suitable to
a thin microchannel to the patterned Ultraviolet light . be used as bioinks [20,46,47] . Here, we only introduce the
[40]
Here, dielectrophoresis is employed to array the cells in inductive nature of various materials. Almost all bioinks
the resin to ensure the uniform distribution of cells in the used currently are composed of polymer components, most
fabricated 2D modules. Moreover, in the fabrication of of which are used in the form of hydrogels. Pure polymers
the 2D modules utilizing soft lithography, the template can be used in bioprinting, but some composite polymers
patterns are first fabricated. Then, by molding the are also used to improve the mechanical properties
templates, poly(dimethylsiloxane) (PDMS) microwell of materials or expand the other physical properties.
arrays are obtained. The PDMS microwell array also Some popular pure polymers are as follows. Collagen
serves as the template for shaping the curable solutions. is a triple helix biocompatible protein of natural origin,
After solidification of the solution, the 2D modules with which has the smallest immune response . Collagen can
[48]
arbitrary shapes can be fabricated [41,42] . also promote cell culture and enhance cell adhesion and
[49]
3.4. Cell sheets attachment to the culture medium . Collagen stays in
a liquid state at a low temperature and will gel when the
Researchers have a wide variety of choices available in temperature rises, but the solidification speed is slow; it
the fabrication of the cell sheets which can also act as the takes 30 min at 37℃ to gel totally, which is a barrier to 3D
modular tissues in the “bottom-up” tissue engineering. bioprinting . Fibrin is a kind of bioink with considerable
[46]
The typical methods include the layer-by-layer covering mechanical properties (especially elasticity) and short
method and the textile method. The layer-by-layer gelation time. It is also biocompatible and able to promote
covering method is one of the simplest approaches to cell growth and is thus a choice to fabricate microvessels.
fabricate the sheet modules. In the research of Yokoyama However, the price of fibrin is also high. Silk is one of
et al., they used elastin to wrap smooth muscle cells the most common biological protein materials, derived
arranged in a multilayer spiral . In the fabrication from biological activities such as spider silk or silkworm
[43]
process, Yokoyama et al. used the layer-by-layer method, cocoons. Silk has ideal mechanical properties while being
as shown in Figure 2D, which cultivates a layer of smooth, non-toxic, and not easy to be contaminated by
smooth muscle cells in the elastin. When the cells are bacteria. However, it usually needs to be mixed with other
proliferated to the required number, they are gelled, and substances to optimize some other important printing
then the second layer of cells is cultivated on it, and so on. properties, such as transparency and fluidity. Alginate is
Hinds et al. used a similar method to fabricate a cell sheet one of the most popular natural hydrogels. It is a natural
and then used it to build a vascular structure . Although polysaccharide with special characteristics such as high
[44]
the fabrication was conducted on a cylinder mold, all the biocompatibility, low price, different crosslinking options,
contents are uploaded layer-by-layer through a syringe. and high compatibility with various printing methods .
[46]
Electrospun uses the electric field to gel the woven elastin Low cell adhesion and average mechanical properties are
fiber. After weaving the fiber gels, the final output is the its two main shortcomings. Chitosan, similar to cellulose,
sheet module. is also a natural polymer polysaccharide, which is generally
used to make tissues or organs with high mechanical
3.5. Bioinks: pure polymers strength (resistance to tension and compression). Its price
In “bottom-up” tissue engineering by bioprinting, the is also very low, and it is often used in the medical field
bioinks are important. The concept of bioinks comes with as well. Gelatin is mainly derived from the hydrolysis
[50]
the development of bioprinting technology. Many studies of collagen. Therefore, it can be directly extracted from
on bioinks in recent years have discovered or developed animal connective tissue and other materials. It has
various materials suitable for bioprinting. In general, bioinks low immunogenicity, no cytotoxicity, and low cost, but

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