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Mir TA, et al.
All of organs arise through a process that begins with the are many excellent scientific researches on generation
fertilized egg which undergoes through cell divisions, of organs based on the embryological phenomena [110-113] ;
differentiation processes resulting in the formation of however, it seems difficult to provide enough organs
organs and ends with a new individual living entity. From for patients with organ failure/disease during the waiting
a pragmatic point of view, there are several factors which period. For these reasons, natural process is generally
directly or indirectly influence the continued growth and considered as unsuitable option for complex tissue and
development of organs (differentiation of the cells into organ regeneration (Figure 2).
two or more histologically specialized structures that Although several tissue engineering approaches have been
organize to form specific organs and organs systems) implemented for various biomedical research strategies,
to the time of delivery. The rate of organ growth and differences in the natural formation of living human tissues/
development varies individually and is dependent on organs with their unique shapes and material properties,
multiple sequential and reciprocal interactive influences hierarchical, morphological, anatomical, and physiological
mediated by genetic structure, genetic information biochemical features limit the ability of conventional tissue
and genetic diversity traits, maternal traits, and engineering approaches to regenerate complex metabolic
internal environmental control mechanisms of the body. organs. In other words, tissues/organs require more
Morphology, histology, and functional anatomy are sophisticated biomimetic 3D microenvironments capable
largely limited to the hierarchical level of organs. Thus, of providing multilayer information to differentiating
the anatomical and histomorphologic features build up cells. Novel biomanufacturing methodologies and
continually according to the growth of the organ and biomimetic materials still need to be developed and be
whole body through many complicated processes across used to assemble microscale building blocks capable of
respective assembly locations in the body. For example, accurately mimicking/replacing 3D complex Humanscale
if you see the complex embryology of heart, it forms living vascularized tissue/organ analogs with optimal
initially in the embryonic disc as a simple paired tube physiological activity.
inside the forming pericardial cavity. However, as it Therefore, bio-AM is the only hope to overcome
develops four chambers with four valves, the complexity these challenges and to simultaneously construct
creates even more complex dynamics of the physiological fully functional organ analogs with great complexity
systems [106-109] . (including histologically essential structures) by
In the natural process inside our bodies, tissue and applying 2D/3D printing and related AM strategies.
structures originate and mature as an individual grows. Although available biofabrication methods have several
Therefore, it is not so easy to establish feasible organs features and capabilities, still there are limitations to
substitute through natural processes because it takes exploit the exact structure/function of the native tissue
many years for an individual and its organs to grow, organ. More complex material distribution and
develop, and generate sufficient functions. In contrasts, construction of anatomically and physiologically relevant
patients who require organ transplants cannot wait for tissues/organs may not be easily achieved without
organs for such a long time. For this reason, organs or advanced biofabrication approaches. To produce a
organ substitutes for transplantation should be provided substitute for natural organ or autologous tissue graft that
as soon as possible, ideally within a few months. There is ready to be transplanted, improvements in biofabrication

Figure 2. The sketch shows a schematic drawing of the strategy of rapid production of the organs beyond the biological natural course.

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