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3D-printed borate glass scaffolds for bone repair
           soft tissue [52,53] . As expected, addition of BMP-2   3D-printed  scaffolds  and  reported  approximately
           significantly  increased  new  bone  formation  to   6% new bone formation . The material extrusion
                                                                                     [55]
           almost 40%, based on the total defect area, and     3D-printed scaffolds had pores in the range 150 –
           almost filled the entirety of the pores. Our results   300 µm unlike the 1 mm pores of the cubic and
           are consistent with a recent study that showed the   diamond scaffolds used in this study. Other studies
           addition of BMP-2 at the same concentration (1 µg   mentioned in Table 4 utilized scaffolds made with
           per defect) to defects treated with HA microspheres   polymer foam replication technique, freeze-drying
           for the same time frame also created approximately   technique, and pressed short fiber technique that
           40% new bone in a 4.6 mm diameter rat calvarial     have significantly smaller pore sizes, thinner strut
           defect .  The  above  study  investigated  the  role   diameters,  and  higher  porosities.  The  amount
                [54]
           of relaxin, a pregnancy hormone, to control and     of bone formation in terms of defect region was
           enhance  BMP-2  release  to  reduce  the  need  for   reported in the range of 9 – 28% after 12 weeks
           high  concentrations  of  BMP-2.  It  was  reported   of  implantation.  A  relatively  higher  amount  of
           that the addition of 0.05 µg of relaxin to 0.5 µg of   bone  formation  (up  to  30%)  was  reported  when
           BMP-2 induced higher bone formation compared        scaffolds were made with copper and zinc doped
           to 1 µg of BMP-2 alone per defect. In the future, a   borate glass. Higher bone growth for all the above
           combination of relaxin and BMP-2 together with      scaffolds could be due to smaller pore size range
           biomimetic architecture (such as diamond) could     and  higher  porosities  compared  to  the  scaffolds
           further enhance bone regeneration and repair.       used in this study, which were limited by the laser
             As  new  bone  formation  was  about  6%  for     spot size of the SLS process. The role of pore size
           both  scaffold  types  without  BMP-2,  the  results   is not completely understood as there exist reports
           obtained  in  this  study  are  largely  in  agreement   with  mixed  results  when  using  scaffolds  with  a
           with  in vivo  assessments  using  borate-based     range of pore sizes for bone regeneration . While
                                                                                                     [28]
           bioactive  glasses  by  other  researchers.  Table  4   some studies have reported that average pore sizes
           concisely summarizes in vivo results using doped    in the range of 100 – 300 µm are effective for bone
           and undoped borate glasses. The implantation time   tissue growth, others have suggested large pores
           for most studies was 8 or 12 weeks, though one      in the range of 600 –1000 µm are better for tissue
           study had a 6-week time point to evaluate the bone   growth [56,57] . Another study suggested a nonlinear
           growth in defect regions using material extrusion   effect of pore size on bone tissue regeneration for


           Table 4. In vivo assessment of borate-based bioactive glasses for bone regeneration.
           Study            Scaffold type    Defect and treatment duration  Porosity (%) and  New bone
                                                                            pore size (µm)   formation
           Gu et al. [55,58]  3D-printed grid-  Φ4.6 mm rat cranial – 6 and 12 weeks 47 and 150 – 300   Grid-like
                           like and pressed                                 (grid-like)      6% (6 weeks)
                           short fibers                                     58 and 50 – 550   9% (12 weeks)
                                                                            (pressed fibers)  pressed fibers
                                                                                             20% (12 weeks)
           Bi et al. [30]  Pressed short fibers Φ4.6 mm rat cranial – 12 weeks  58 and 50 – 500  15%
           Bi et al. [59]  3D-printed grid-  6 mm femur                     50 and 140 – 250   26% (grid-like) and
                           like and freeze   12 weeks                       (grid-like)      28% (freeze drying)
                           drying                                           47 and 50 – 150
                                                                            (freeze drying)
           Wang et al. [60,61]  Polymer foam   Φ5.0 mm rat cranial – 8 weeks  80 – 89 and 200   16% (undoped)
                           replication                                      – 400            29% (Zn doped)
                                                                                             30% (Cu coped)
           This study      SLS              Φ4.6 mm rat cranial – 6 weeks   47 – 54 and 1000  6% (no BMP-2)
                                                                                             40% (BMP-2)

           94                          International Journal of Bioprinting (2020)–Volume 6, Issue 2
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