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In vitro model of the glial scar
           and  filling.  Thus,  the  proposed  3D  collagen  gel  tissue   the increase of culture time. Tallinen et al.  used a similar
                                                                                                 [29]
           constructed with astrocytes has scar formation properties,   principle to construct a fold model of the human brain
           and the glial scars are mainly produced by astrocytes.   from a macro perspective. At this stage, the cells traction
           It is quite coincidental  that the similar phenomenon   caused the deformation of the extracellular matrix [30-32] ,
           of  tissue  shrinking  also  occurs  in  the  brain  of  a  Sorex   resulting  in  a  stronger  collagen  fiber  aggregation.
           araneus. Scientists have discovered that the skull of the   With  different  initial  cell  concentrations,  the  degree  of
           Sorex  araneus  pup  shrinks  in  the  late  summer,  as  well   reduction is also different. The higher the concentration,
           as the brain, whose weight is also reduced. During the   the  more cells proliferate  and migrate,  and the  more
           winter, the part of brain lost can grow back partly. This   seriously  the  gel  tissue  shrinks.  The  collagen  gel  with
           phenomenon  is called  Dehnel’s phenomenon [26-28] . It is   astrocytes shrinks due to cell proliferation and migration.
           similar to the results of this article, occurring in the brain.   Consequently, the collagen fibers gradually extrude each
           To a certain extent, it may provide some reference for   other,  the  surface  pores  disappear,  and  the  fiber  pores
           the study of brain plasticity and evolution. It may have a   decrease. Meanwhile, the surface of the collagen gel is
           certain value for reference to the study of brain plasticity   deformed to form a relatively solid and wrinkled surface
           and evolution.                                      because of the movement of the cells. The process of gel
                                                                                                            [33]
             On the basis of this shrinkage, the folds can be found   contraction is similar to the course of wound healing .
           on the surface of the block, and the pores are reduced with   The force produced by cell proliferation and migration
                                                               does not affect the collagen gel without cells. Hence, the
                                                               surface remains flat and porous. In addition, the shrinkage
                                                               rates  of  blocks  with  different  concentration  astrocytes
                                                               were relatively similar on day 8, but the moduli of them
                                                               were quite different. This indicates that the concentration
                                                               of cells also has a certain effect on the modulus when the
                                                               collagen gel shrinks. The higher the cell concentration,
                                                               the  larger  the  collagen  tissue  modulus.  From  this,  the
                                                               reason  for collagen  gel  macroscopic  and  microscopic
                                                               size-changing can be inferred (Figure  10). The  results
                                                               of the experiment  can  demonstrate  that  the  model  we
                                                               constructed can form glial scars.
                                                               5. Conclusion

                                                               In this study, a  3D astrocytes  model  with  collagen
                                                               gel  in vitro has been constructed.  This model shows
           Figure 9. The hypertrophic cytoplasm of astrocytes embedded in   the characteristics  of the glial scar (hypertrophy and
           collagen gel on day 8, astrocytes were stained by glial fibrillary   hyperplasia). The constructed 3D model reveals overall
           acidic protein in green, nuclei were stained by DAPI in blue, Scale   shrinkage with the prolongation of culture time. On the
           bars: 50 μm.                                        other  hand,  the  shrinkage  rate  and  compression  elastic























           Figure 10. The reason for collagen gel block size changing from macroscopic and microscopic.

           96                          International Journal of Bioprinting (2019)–Volume 5, Issue 2
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