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Roles of support materials in 3D bioprinting — Present and future

            for bioprinted 3D complex hollow structures.       ing a human organ. This is due to the fact that only
                                                               one of the materials, either model or support materials
            2. Roles of Support Materials in Bioprinting       (mostly  support  material),  has  the  good  mechanical

            Recently,  printing  beyond  2.5D  (2.5D  shape  is  the   strength  which  is  responsible  for  the  shape  stability
            shape that comes from repeatedly printing a 2D pat-  and shape integrity.
            tern in Z direction without changing the pattern in any   Another recent advancement is the development of
            layer)  grid  structure  and  simple  tubes  into  the  mi-  freeform  reversible  embedding  of  suspended  hydro-
            cro-channeled and hollow structures represent a great   gels or  “FRESH”  technique,  which allows 3D  struc-
            advancement  in  bioprinting [10,11] .  It  is  no l onger   ture to be fabricated by using gelatin bath as the sup-
            stacking layer by layer in the same pattern. To form   port  material  with  many  types  of  other  hydrogels  as
            small channels or hollow tubes, a second “bioink” is   model  materials  such  as  alginate  with  calcium  chlo-
                                                                                                 [13]
            used.  The  second  bioink  acts  as  support  material  or   ride (CaCl 2) or fibrinogen and thrombin  . However,
            sacrificial material. As shown in Figure 1, the second   this technique needs precision control in temperature
            ink  acts  as  mold  or  sacrificial  materials  to  create  a   in  addition  to  positional  control.  Gelatin  is  ther-
            hollow structure or track for perfusion purpose. This   mo-responsive which will start to melt when the tem-
                                                                                   [2]
            technique  normally  composes  of  chemically  cros-  perature is above 30 °C . Therefore, temperature con-
            slinked hydrogel especially UV crosslinked hydrogel   trol is critical for “FRESH”. Moreover, the “FRESH”
            such  as  GelMA [11]   or  polyethylene  glycol  diacrylate   technique is batch by batch specific so the crosslinked
            (PEGDA)  [12]   as  model  materials  and  usually  ther-  agent must be pre-mixed with gelatin bath first. Last-
            mo-responsive  hydrogels  such  as  pluronic  F127  or   ly,  because  of  gelatin  bath,  the  printing  temperature
                                     [2]
            agarose as support materials . By incorporating both   needs to be lower than 30 °C (around 22–25 °C) which
            types  of  hydrogels,  the  complex  hollow  or  complex   is not ideal for printing cells over a prolonged period.
            track  pattern  in  2.5D  level  or  microfluidic  level  is   To date, “FRESH” is considered one of the most ad-
            possible to be fabricated.                         vanced techniques. To sum up, a list of support mate-
               Even though the complex track has more advance-  rials for bioprinting is shown in Table 1.
            ment  compared  to  just  2.5D  lattice  structure,  in  the   Here  comes  the  question,  what  is  the  next  ad-
            reality, the real human organ is never in 2.5D plane.   vancement for support material in bioprinting? In 3D
            Rather, human organ is an intricate 3D structure which   printing,  support  materials  always  play  an  important
            has a very complex shape, fine details and topography.   role to create overhanging and hollow structures. As
            Therefore, the technique in Figure 1 is not sufficiently   shown in Figure 2 which is an anatomical heart model,
            adequate to bring 3D bioprinting to the level of print-  the overhanging part (Figure 2A) needs a support to


























            Figure 1. Schematic of hollow structure or track fabrication using two different types of hydrogels. UV curable hydrogel is model
            material whereas thermo-responsive hydrogel is sacrificial materials.
            84                          International Journal of Bioprinting (2017)–Volume 3, Issue 1
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