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Application of Machine Learning in 3D Bioprinting
           and  virtual  shadow.  Creating  such  cell-level  twins  of   Interestingly, ML had been applied to nanotechnology
           organs requires high quality tissue specimens and advanced   to develop nanocomputing  hardware that  can boost
           imaging and 3D reconstruction methods. Fortunately, the   artificial-intelligence-based  applications . It could  be
                                                                                                 [29]
           Human BioMolecular  Atlas Program from Institute of   a reciprocal  advancement  to expect  in future. Another
           Health in the United States , which aims to develop an   topic worth watching is ML-based programmable design
                                  [23]
           open and global framework to create 3D molecular and   for 4D printing , as it is relevant to 4D bioprinting, a
                                                                            [30]
           cellular atlas of the human body, may enable the building   method in which bioprinted tissues transform shape, size,
           of an integrated tissue map across scales. However, as   or pattern over time . Aside from academy, the industry
                                                                               [31]
           pointed out in Campos and De Laporte , digital tissues   also expects a bright future for use of artificial intelligence
                                            [8]
           should not only enable architectural replication of native   in 3D bioprinting. For example,  in 2019 Procter  and
           tissues but also be biologically functional.  This would   Gamble partnered with a biotechnology company Aether
           require  the  capability  of  assigning  fidelitous  tissue   to develop AI 3D Bioprinter .
                                                                                      [32]
           materials to the digital twin and a profound understanding
           of  individual  and  collective  behaviors  of  cells.  Cell-  6. Toward digital bioprinting
           based mathematical models and software , which have   Application  of ML in bioprinting  and biofabrication
                                              [24]
           been extensively used in computational biology, may be   will induce dramatic  transformation  and bioprinting
           useful tools for modeling cell and tissue properties and   will  became  a part  of digital  industry  and information
           behaviors to enable the simulation of biological functions   technology [33,34] .  What  could be done to implement
           of the virtual tissue and organs. In fact, from the economic   these forthcoming transformations? First, bioprinting
           point of view, an alternative but efficient method should   community must attract  experts in computer sciences,
           be one that directly converts current magnetic resonance   mathematical modeling, computer simulations, and ML.
           imaging (MRI)/confidence interval-based 3D models into   Second, special efforts must be done for generation,
           cell-based models, that is, cells and tissue properties are   assembly  and maintaining  of desirable  Big  Data.
           intelligently assigned to a virtual organ model with spatial   Maintaining and up-dating of such databases are essential.
           accuracy  and  material  diversity  by  artificial  intelligent   Third,  digital  organ  twins  based  on  sophisticated
           algorithms. Slicing of the digital twin for layer-by-layer   mathematical  modeling  and advanced  software
           bioprinting should also be intact cell-based and matching   will  become  a  new  type  of  knowledge  presentation,
           extrusion  layer  thickness,  which  is  very  different  from   accumulation,  and  compaction in bioprinting.  Finally,
           common slicing in 3D printing. Another alternative further   during transition from empiric to digital  approach
           empowering our imagination is in vivo cellular imaging   bioprinting will enter in digital era and it will become not
           such as MRI , which can map the anatomic locations of   descriptive but rather predictive technology increasingly
                     [25]
           specific cells within living tissue. Given that ML has been   based on virtual or in silico experiments.
           successfully used for recognition of cell phenotype , it
                                                      [26]
           might be reasonable to imagine “in vivo 3D scan” of a   7. Conclusion
           patent-specific live tissue model into a digital twin with
           cellular resolution. Nevertheless, the immediate impact of   In our opinion, when applying ML to bioprinting  the
           the digital twins of organs on bioprinting is that the in vivo   most important and urgent challenges are: (1) To build
           performance of physical bioprinting such as preclinical   training  databases for ML from  Big  Data  curation  and
           as well as clinical studies must collect information with   (2) to build digital  twins of human tissue/organs.  The
           specially designed assay, biosensor, and so on for updating   goal is to achieve a predictive power of digital twin of
           original model in the form of digital twin. Furthermore,   human tissue/organ based on Big Data which is close to
           the  cell-level  digital  twins  together  with  physical  3D   virtual crash test in automobile industry. Ultimately, we
           bioprinting could also revolutionize biology fundamentally   hope to see a standard bioprinting simulation practice in
           by building tissues from scratch to explore entirely   future to reduce or replace present 3D bioprinting studies.
           new  cell  configurations  for  cell  cross-talks  and  cellular   We envision that future 3D bioprinting will become more
           morphogenesis . This would help provide new insights   digital and  in silico, and eventually  strike a balance
                       [27]
           into the challenging question: “Print me an organ! Why we   between virtual and physical experiments to maximize the
           are not there yet?” which was recently raised in Ng et al. .  efficiency  of  bioprinting  resource  utilization.  In  future,
                                                        [28]
                                                               digital bioprinting will become a new growth point for
           5. Other aspects of the future                      digital industry and information technology.
           In future, it is necessary to include the development of   References
           correspondent  infrastructures  such as education  and
           training specialists and development and adaptation   1.   Yu C, Jiang J, 2020,  A Perspective  on Using Machine
           of software and computational  power and so on.         Learning in 3D Bioprinting. Int J Bioprinting, 6:95.

           4                           International Journal of Bioprinting (2021)–Volume 7, Issue 1
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