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Biofabrication offers future hope for tackling various obstacles and challenges in tissue engineering and regenerative medicine: A Perspective
           technologies  for facilitating  the  precise  programmable   It is often thought that the  in vivo approaches are
           designing,  computer-controlled  efficient  biofabrication,   physiologically better and look realistic enough.
           and post-fabrication incubation are urgently needed. There   However, this is not necessarily true and in vivo approaches
           is still a long way to go in fabricating bioartificial organs   are not always better for organ engineering. One of the main
           on demand, but these technologies are achievable.  If   limitations of  in vivo approaches for tissue engineering
           biofabrication approaches will work out, it will become   research  is  the  regeneration  of  only  fibrous  tissues.  It
           possible to fabricate  not only Humanscale  patient-  has been demonstrated that fibroblasts and inflammatory
           specific tissue grafts/organs at a rapid pace (irrespective   cells are the most strongly proliferating cells in the living
           of organ size) but it will also shorten the time required of   body consuming large amount of nutrients and oxygen to
           growth performance and development of organs. Then, no   provide  energy  for  proliferation  of  metabolically  active
           patient will ever have to wait on lengthy transplant lists   cells [114-116] .  Therefore, the transplanted cells cannot
           for donor organs, and no patient will ever have to take   survive without a blood  supply,  sufficient supply  of
           powerful, debilitating and potentially fatal drugs to treat   essential nutrients, or adequate means for waste product
           chronic  pains and to prevent their  immune  systems   removal. Instead, outside the body, the desired tissues or
           from rejecting  new body parts or from attacking  the   organs can be grown without pro-fibrogenic environment.
           transplanted organ when the organ is not closely matched.  Therefore, better in vitro strategies are really needed to
                                                               support, instruct, and maintain cells inside immune-
           1.5. Challenge to Extracorporeal Organ Engineering  privileged 3D microenvironments, where cultured cells
           In conventional  TERM  methods  including  cell     do not lose their unique intrinsic characteristics (Figure 3).
           transplantation  and the scaffold-based tissue repair   As mentioned  above,  bioprinting  is the  only  hope  for
           strategies, morphogenesis of tissue architectures  and   fabricating  appropriate  environments  for cells  to  be
           regulation  of essential  biochemical and physiological   able  to  effectively  produce  spare  parts  of the  human
           processes all depends on the regenerative  ability of   tissue/organs  beyond the  limits  attained  in  vivo.  For
           cells  and  the  recipient  in  vivo.  While  modern  tissue   instance, biofabricated  organs can be incubated  in the
           engineering approaches are good at making tissues in the   environment under the high or low oxygen tension, high
           laboratory, we still cannot control the important processes   or low growth factors, and exposure of drugs which
           of complex  tissue and organ after  implantation. Here   have  high  pharmacological  activity.  Control  of  such
           comes the role of bio-AM filed to make extracorporeal   incubating  parameters  is impossible  in vivo situations
           systems having  the  capability  to  repair/return organ   due to harmful effects on the recipients. Therefore, the
           function permanently or   for implantation.   Broadly   concept of extracorporeal system is clinically appealing
           speaking, bio-AM is aiming at challenges of producing   and advanced extracorporeal systems are necessary for
           extracorporeal  organ reconstruction  systems, in which   biofabrication research. Such systems may enable precise
           the important tissue structures can be printed, fabricated,   spatial and temporal control arbitrarily without affecting
           assembled,  cultured, and matured before implantation.   the recipients.  Building on this momentum,  the next
           In addition, ideally, the functions of engineered organs   regenerative medicine frontier lies in how biofabrication
           should also be established before implantation.     researchers  can  better  develop  novel  extracorporeal

























           Figure 3. The sketch shows a schematic drawing of the general culture strategy and organ perfusion bioreactor technology.

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