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3D-printed bioreactors for in vitro modeling and analysis
           complex microfabrication processes.  Another        carrier , have been shown to stimulate microbial
                                                                     [63]
           group developed  a 3D-printed  smartphone           assemblages for improved organic matter removal
           platform  integrated  with  an  optoelectrowetting-  and better performance of biofilm reactors. Other
           operated microfluidic device for on-site detection   studies employed SLA-printed miniature anaerobic
           of viable algae cells .  The  collected  data  were   digester reactors as a process screening tool for
                               [52]
           wirelessly transmitted to a central host for real-time   sustainable treatment of wastewater and biowaste .
                                                                                                            [62]
           monitoring of water quality with reduced analysis
           time.  Given  its  sensitivity,  this  chip  allowed   3 Conclusions and future directions
           sample preparation methods such as droplet
           immobilization and mixing, target cell counting,    In  recent  years,  significant  advances  have  been
           and fluorescent detection.                          made  in 3D-printed  bioreactor  technologies.
                                                               Bioreactors  have been tailored to easy online
           2.2.3 3D-printed bioreactor for pathogen            monitoring and automated bioprocesses, thereby
                 phenotypic analysis                           closing the gap between conventional bioreactors

           Profiling  pathogen  phenotypes  is  important  in   and their  miniature  3D-printed  counterparts.
           decoding the virulence and interaction of pathogen   However, in addition to their basic functions, other
           with  its  surroundings.  A  propidium  monoazide   design  aspects,  such  as  flexible  operation  and
           (PMA)  pretreatment  was  carried  out  in  a  3D-  process optimization, should be taken into account,
           printed bioreactor to efficiently discriminate live   especially  for devices used to study complex
           waterborne  bacterial  pathogens  in  natural  pond   physiological  phenomena.  It  is  noteworthy  to
           water  samples .  The material jetted  bioreactor   mention that there has been limited  clinical
                         [60]
           was  designed  with  an  inlet,  splitter,  and  mixers   translation of 3D-printed bioreactors. This could
           for  proper  sample-PMA  mixing  followed  by       be attributed to the lack of optimized protocols that
           incubation  in serpentine channels  containing      are fine-tuned to respective 3D-printing methods
           herringbone structures for alternating  dark and    and materials. The reproducibility of certain 3D-
           light incubation.  The results obtained from this   printing processes is suboptimal.
           3D-printed  bioreactor  suggested  the  need  for     At present, 3D-printing research for  in vitro
           species-specific  optimization  of  pretreatment    biological applications focuses mostly on relatively
           performance.    Elsewhere,    an   SLA-printed      simple systems that only incorporate a limited
           incubation/diffusion  chamber  was  designed  for   number of cells and cell types. Future studies
           culturing bacteria from soil samples to study their   should aim to attend to relatively complex tissues
           interaction  dynamics.  The chamber  facilitated    and organs. Moreover, several concerns such as
           diffusion of soil components with target cells and   3D-printing compatible design, removal of support
           also  allowed  single-cell  and  ensemble  bacterial   structures, the choice of appropriate cell lines, better
           phenotypic analyses .
                              [61]
                                                               cocultivation concepts, establishment of optimal
           2.2.4 3D-printed bioreactor for wastewater          conditions, and protocol standardization remain to be
                 treatment                                     resolved and should be the focus of future research.

           Several 3D-printed bioreactors have demonstrated    With advances in various aspects of 3D-printing,
           great  potential  in  water  treatment  applications   one  would  be  able  to  design  and  manufacture
           that were difficult to be achieved by conventional   customized bioreactors with tailored functionalities
           wastewater    treatment   systems.   Cylindrical    using  3D-printing  in  laboratory  settings,  which
           microrobots    printed   by    SLA     conveyed     would significantly drive future biomedical research
           excellent  water  purification  capability  and  great   by offering on-demand in vitro testing.
           biocompatibility  with  mammalian  cells . Other    Conflicts of interest
                                                 [26]
           intricate 3D-printed bioreactor designs, including
           fullerene-shaped bio-carriers  and gyroid-shaped    The authors declare no conflicts of interest.
                                      [21]
           92                          International Journal of Bioprinting (2020)–Volume 6, Issue 4
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