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Mir TA, et al.
of tissue engineering and future studies could prove and adequate integration of biological tissue components
“whether human beings can produce organs using printing with their application contexts are also needed to obtain
and manufacturing techniques.” In this mini review paper, biologically active 2D/3D tissues and organs or related
we have focused on various challenges which need to be bioproducts, but as yet, such materials have never been
overcome by bioprinting and biofabrication to produce utilized in usual AM purposes [54-57] . There is no doubt that
organ or organ substitutes. all of the AM procedures required to be carried out in
biologically safe environment. Although bio-AM can be
3.1. Challenge of Producing Organs by AM helpful for the biomanufacturing, there are practically no
In bioprinting and biofabrication, 3D tissues and organs are established 3D biofabrication machines which can realize
constructed by aligning living cells and biomaterials and the manufacturing of arbitrary 3D structures. Therefore,
by stacking or laminating them in 3D [51,52] . Such bottom-up it is necessary to develop advanced biofabrication
fabrication method of building 3D structures is called AM. machines to achieve the goal of arranging several different
Most of the conventional manufacturing techniques used materials (including cells) in 3D space for engineering of
to build 3D objects are based on molding and subtractive multicellular constructs (tissues/organs) or bioproducts
methods. By traditional manufacturing, 3D shapes can be on demand. Apparently, a growing number of 3D printers
made by starting from an object having an initial size or have entered into the mainstream biomanufacturing
shape, materials are often molded, carved out, or removed technology, but only extrusion-based bioprinting (EBB)
by a sharp cutting tool until product of the desired shape is is rapidly growing [21,22,24,37,43,45] . Even though EBB is
formed. However, there are still challenging issues considered to be the most accepted technique in tissue
associated with these methods, especially the inability to engineering field to date, this technique also suffers
create or control the internal structure of the 3D objects. from several limitations. For example, the resolution
When it comes to manufacturing of 3D structures of extrusion type printers is still very poor (more than
that specifically mimic human tissue- and organ- 500 μm) [41,44,58-78] . On the other hand, an average human
specific microarchitecture, these conventional approaches cells range in size from about 10 to 30 µm, while very
certainly are not useful because all vital organs are highly fine capillary vessels, which are the essential tissue
complex in nature, and each individual organ possesses components are on the order of 10 µm in diameter.
its own specialized microsized histological, anatomical, Therefore, 3D bioprinters with sufficient resolution
and morphological structures which are very essential to ability are needed, ultimately.
[53]
perform all organ-specific physiological activities . In addition, diverse bioink formulation is also one of the
Therefore, the technologies to construct 3D structure challenging aspects of this field. Typical adult human
both internal and external structures simultaneously body consists of myriad of cell populations, tissue
are highly needed for TERM research. As such, any components, and microstructures that work together to
structure we fabricate needs to exactly match that level perform particular body functions. At present, effective
of complex structural heterogeneity. Thus, the only materials for bioink of 3D bioprinting or biofabrication
hope for generating such structures is AM technology. are extremely limited, the reader is referred to more
For this reason, bioprinting and biofabrication have specialized reports [54,56,57,79] . Therefore, the development
ever being challenged to produce organs or their spare and formulation of effective bioinks are necessary
bioparts by AM approach. As mentioned in Groll for the clinical application of bioprinting technology.
et al. (2016), bioprinting is a complimentary strategy More importantly, novel kind of hydrogel materials
within biofabrication. With bio-AM, this term can be exhibiting remarkably favorable properties, including
used for describing a holistic approach that combines compatibility with different bioprinting methods, rapid or
both bioprinting and biofabrication technologies for instantaneous gelling properties, flexibility and stability
constructing engineered tissues/organs. Indeed, bio-AM in medium, cytocompatibility, or biofunctionality, are still
has the potential to transform global health care and needed for proper cell growth, differentiation, and tissue
medicine, but bio-AM is still in its infancy and there are formation or regeneration during bioprinting processes
several obvious challenges that need to be overcome. (pre-bioprinting, bioprinting, and post-bioprinting).
Since such AM techniques have been only recently The formulation of wide range of the biomaterials
proposed and developed, only limited research is reported to design a variety of bioinks exhibiting the above-
on their application for realizing truly biologically mentioned properties remains an important research
inspired new engineering solutions for clinical health direction for biofabrication research. Nowadays, bioink
care and bioindustry. is one of the emerging and hot topics in bioprinting and
Although biological materials, especially living cells, can biofabrication [80,81] . Expanding biofabrication technology
be regarded as the key materials for bio-AM, several and fostering the invention of new biomanufacturing
other well-controlled and biocompatible biomaterials, machines and development of novel bioink materials

International Journal of Bioprinting (2019)–Volume 5, Issue 1 3