3D bioprinting for cell culture and tissue fabrication
Bio-Design and Manufacturing (2018) 1:45–61
https://doi.org/10.1007/s42242-018-0006-1
REVIEW
3D bioprinting for cell culture and tissue fabrication
Honglei Jian1 · Meiyue Wang1 · Shengtao Wang1 · Anhe Wang1 · Shuo Bai1
Received: 9 January 2018 / Accepted: 27 January 2018 / Published online: 26 February 2018
© Zhejiang University Press 2018
Abstract
Three-dimensional (3D) bioprinting is a computer-assisted technology which precisely controls spatial position of biomaterials, growth factors and living cells, offering unprecedented possibility to bridge the gap between structurally mimic tissue
constructs and functional tissues or organoids. We briefly focus on diverse bioinks used in the recent progresses of biofabrication and 3D bioprinting of various tissue architectures including blood vessel, bone, cartilage, skin, heart, liver and nerve
systems. This paper provides readers a guideline with the conjunction between bioinks and the targeted tissue or organ types
in structuration and final functionalization of these tissue analogues. The challenges and perspectives in 3D bioprinting field
are also illustrated.
Keywords 3D bioprinting · Bioink · Cell culture · Tissue fabrication · Organoid
Introduction
Three-dimensional (3D) bioprinting, a computer-assisted
technology, is able to precisely control spatial position of
biomaterials, growth factors and living cells with an ultimate goal of creating functional tissues and organs [1,2].
3D bioprinting is becoming more and more popular in tissue
fabrication because of its capacity of using customized structures and autologous cells to directly produce complex and
biomimetic tissue architectures [3,4]. During printing process, the biomaterials made for living cells that behave much
like a liquid allowing to “print” into a desired shape, are called
bioinks. 3D bioprinting technology offers unprecedented
possibility to bridge the gap between structurally mimic tissue constructs and functional tissues or organoids [5–7].
According to the employed printing mechanisms, the
bioprinting techniques for tissue fabrication are classified
into three main types: extrusion-, droplet- and laser- based
bioprinting process [8]. In general, extrusion-based bioprinting, perhaps the most widespread method for fabrication,
Honglei Jian and Meiyue Wang have contributed equally to this work.
B Shuo Bai
1
State Key Laboratory of Biochemical Engineering, Institute
of Process Engineering, Chinese Academy of Sciences,
Beijing 100190, China
depends on mechanical-, pneumatic- or solenoid-driven
micro-extrusion to create continuous strands of bioink [9].
In droplet-based bioprinting, various kinds of energy sources
covering thermal, piezoelectric, electrostatic, hydrodynamic,
acoustic and microvalve are employed to generate droplets
of bioink [10]. In the case of laser-based bioprinting, laser
energy is utilized for high-precision deposition of bioinks
[11]. These bioprinting processes have their respective printing features and requirements of suitable inks [12], which
are summarized in Table 1.
With regard to the fabrication of a desired tissue or
organoid, the consideration about the suitable bioink features
is far beyond the choice of a suitable bioprinting process.
When a biomaterial is printed onto the substrate (i.e., the
receiving surface), it needs to undergo a fast phase transition to preserve the shape and resolution, and thereafter
maintain cell viability and proliferation during post-printing
incubation [13], which is one of the most important features
distinguishing injectable and printable hydrogel material
[14,15]. The structural and functional diversity of tissue
fabrication leads to a wide development of bioink. The
major bioink material used in tissue biofabrication and 3D
bioprinting is hydrogel matrix and usually nature-derived.
It is because of that high-water content of hydrogel, up
to 1000 times of their original weight in aqueous media
[16], enables well penetration of oxygen, nutrients, growth
factors and other water-soluble components, thereby making them very suitable for tissue or organoid fabrication
[17].
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Table 1 Types and features of bioprinting techniques [8,12]
Types of bioprinting
Extrusion-based
Requirements of bioink
Viscosity < 6 × 107 mPa s, shear
Viscosity < 15 mPa s, rheopectic Viscosity < 300 mPa s, viscoelasticity,
thinning, thixotropic behavior, low
behavior, nonfibrous nature,
intermediate adhesion, low surface
surface tension and adhesion, rapid medium surface tension, rapid
tension, absorption of laser kinetic
gelation, shape retention
gelation
energy, rapid gelation
Requirements of substrate
Wettability, high surface roughness
Wettability, high surface
roughness, induces viscous
forces
Wettability, high surface roughness,
induces viscous forces
Printing speed
Slow
Medium
Fast
Cell density
High, spheroids
< 106 cells/mL
< 108 cells/mL
Post-printing cell viability
∼ 80%
> 85%
95%
Cost
Medium
Low
High
Recent advances in bioink materials for constructing 3D
cell environments have greatly promoted the development
of tissue engineering. The printability of the biomaterials heavily relies on their inherent mechanical properties
such as rheological properties [18–20], bioactive moieties
[21,22] and degradation behavior. For instance, the rheological properties of a bioink have a direct influence on
printability, compatibility, shear stress yielded by cell encapsulation, as well as structural integrity and resolution of 3D
printed construct [23]. The gelation process of a bioink matrix
has a crucial role in both the resolution and cell viability
[24]. Furthermore, the mechanical properties and degradation behavior not only affect cell growth, proliferation and
differentiation, but also long-term biocompatibility in the
fabricated tissues [25–28].
Although 3D bioprinting has made some attractive
progress in tissue fabrication, this technique has not yet
been used to make a lab-to-clinic translation. This paper
reviews the recent progresses in 3D bioprinting from the
perspective of tissue and organoid biofabrication. When
planning for bioprinting, one should first consider the
microenvironment characteristics and cell types of the targeted tissue or organ, and thereafter choose suitable bioink
materials and a rational printing strategy. Therefore, we
briefly focus on the diverse bioinks used for biofabrication of tissues and organoid including blood vessel, bone,
cartilage, skin, heart, liver and nerve. The paper provides
readers a guideline with the conjunction between bioinks
and the targeted tissue or organ types in structuration and
final functionalization of these tissue analogues. The challenges and perspectives in 3D bioprinting field are also
illustrated.
Bioprinting of blood vessel
The vascular networks exist in almost all organs of the
human body, playing crucial roles in nutrient transport and
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Droplet-based
Las (...truncated)