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     Software for bioprinting
           includes analysis of biological data such as cell   space, the object boundary is named “implicit
           populations, genetic sequences, or others to        surface.” Any algorithm or function can be used
           make new prediction. There are researches about     until it can return a real value. Functions in the
           genome data analysis and computational biology      FRep approach form a system where different
           algorithms [125] , development of some pattern-     materials and other parameters can be described.
           based system prototypes , and also hierarchical     The FRep approach is a suitable method to provide
                                  [90]
           modeling with supporting composite modeling [126] .   a heterogeneous representation of objects with any
           The progress in computation biology could be also   complexity. Besides, a mammalian cell colony was
           accelerated by integrating with machine learning    simulated using the FRep approach [132] . The colony
           and other research fields, which are traditionally   was modeled as a set of deformable particles, which
           related to data science [127] . As for computational   are contacting with each other.  A new particles
           approaches for biofabrication, computational fluid   pair, which models the process of cell division, can
           dynamics software packages are widely used to       substitute an existed before particle. This simulation
           calculate  flow  fields,  shear  stresses,  and  mass   has specific features such as real functions that define
           transport with and around 3D bioconstructs and      arbitrary shapes of particles and particular rules of
           bioreactor environments [119] .                     particles’ behavior. A collision detection algorithm
             Nonetheless, the most crucial tools in the field   was  used  to  define  communication  between
           of computational biology for the 3D bioprinting     particles. To solve of the packing problem, a genetic
           are computational  methods such as analytical       algorithm  was  used.  Changing  the  particle  shape,
           methods, mathematical modeling, and simulation      size, and orientation was used for the simulation
           on all 3D bioprinting stages such as pre-processing,   of a deformable particle. One of the figures of the
           processing, and post-processing.                    simulation is presented in Figure 3 [132] .
                                                                 Therefore,  the  FRep approach  represents  a
           4.5 Approaches for future development               method that could help to solve such crucial
           According  to  Robu  et  al. [109] ,  the  software  that   issues in bioprinting as the heterogeneous volume
           controls the bioprinter and, in general, includes   modeling  of living tissues and whole organs.
           of CAD or CAM software now should include a         Besides in the living objects modeling, the FRep
           module for simulation to predict the evolution of the   approach allows us to model various cellular
           printed construct. However, nowadays, bioprinting   structures that  are very important  for implants
           software usually can offer either only control or only   modeling. The example of the cellular structure,
           simulation. Besides, the software for simulation in   developed with the FRep approach, is presented in
           bioprinting is not so widespread. The solution of this
           problem could be developing such software that will
           include ability to work on all necessary stages. It
           should be able to provide control of the bioprinting
           process. Besides, it should have a module for
           simulation, and a slicer that can work with model
           file  formats  that  are  suitable  for  heterogeneous
           volume modeling in bioprinting. FRep has shown
           appropriate method to solve this issue [128-130] . FRep
           can define an object by a continuous function
                             f(x ,x ...,x )             (1)
                                1
                                  2
                                      n
             where f is a real continuous function defined on
           n-dimensional Euclidean space E  that must have     Figure  3.  Simulated  with  the  help  of  function
                                           n
           positive values inside the object, negative values   representation  approach    mammalian      cell
           outside, and zero on the surface [130,131] . In the 3D   colony [132] .
           52                          International Journal of Bioprinting (2020)–Volume 6, Issue 3
     	
