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International Journal of Bioprinting                                Progress in bioprinted ear reconstruction




            Table 2. Continued
             Study       Aim of study        Study   Animal   Study focus  3D printing   Components  Printed                     Printed   Cell nature/type  Notable post-  Assessment   Findings                    Limitations and suggested
                                             setting  model (if        technique                   shape                         material                printing       of success/                                  improvements
                                                   any)                                                                                                  modifications  integration
             Mukherjee et al.   To assess the degradation   In vitro;  Sheep   Direct printing  Extrusion  Cells in bioink +   Other shape  PCL  N/A     None           Histopathology;  •  Both porous 3D-printed PCL and hybrid   The inclusion of GelMA-
             (2021)  [21]  behavior and tissue   in vivo   (similar                  scaffold printed                                                                   ultrasound    scaffolds showed similar and homogenous   HAMA with the PCL
                         compatibility of hybrid   animal  fascial                   together; scaffold                                                                 scan; micro-CT   degradation in vitro. In vivo, they exhibited   demonstrated better
                         scaffolds (PCL-hydrogel)   anatomy)                         only                                                                               scan; electron   minimal irritation or inflammation in   tissue ingrowth. However,
                         compared to single                                                                                                                             microscopy    surrounding tissue over a 6-month period   its impact on cellular
                         material PCL scaffolds in                                                                                                                                    in an immunocompetent animal model that   differentiation can only
                         vitro and in vivo. The study                                                                                                                                 closely resembles human soft tissue biology,   be evaluated in future
                         wanted to understand                                                                                                                                         although the host response varied between   experiments embedded
                         the biological reaction                                                                                                                                      animals.                       with cells.
                         to printed scaffolds                                                                                                                                       •  The hybrid scaffolds had a higher percentage
                         (independent of stem cells)                                                                                                                                  mass loss than control scaffolds due to
                         in an immunocompetent                                                                                                                                        the presence of degrading hydrogels that
                         host.                                                                                                                                                        contributed to a higher initial weight.
                                                                                                                                                                                      However, the degradation profile was
                                                                                                                                                                                      dominated by PCL in both hybrid and PCL-
                                                                                                                                                                                      only scaffolds.
                                                                                                                                                                                    •  SEM showed that degradation occurred from
                                                                                                                                                                                      the outer surface inward for each strand.
                                                                                                                                                                                    •  In vivo, the scaffolds were well tolerated for
                                                                                                                                                                                      the duration of the experiment, with serial
                                                                                                                                                                                      ultrasound and CT scans showing minimal
                                                                                                                                                                                      reaction in surrounding subcutaneous
                                                                                                                                                                                      tissue over 6 months. Ex vivo, the scaffolds
                                                                                                                                                                                      displayed localized hyperemia with peripheral
                                                                                                                                                                                      pallor and pseudo-capsule formation,
                                                                                                                                                                                      consistent with a localized inflammatory
                                                                                                                                                                                      response, indicating good biocompatible
                                                                                                                                                                                      properties with no macroscopic differences
                                                                                                                                                                                      between test and control samples.
                                                                                                                                                                                    •  Control specimens, when 3D-reconstructed,
                                                                                                                                                                                      had less tissue integration compared to all
                                                                                                                                                                                      test samples in both sheep, regardless of PCL
                                                                                                                                                                                      configuration. This may be attributed to the
                                                                                                                                                                                      presence of the hydrogel.
             Tang et al.    To explore the use of   In vitro;  Mice  Direct printing  Fused deposition   Scaffold printed   Resembling   PLA  Rabbit ear   XX           Histopathology;  •  The successful induction of auricular   Short-term study and
             (2021)  [15]  3D printing to fabricate   in vivo          modeling      first and then   pinna                                chondrocytes;                mechanical    chondrogenesis in vivo was demonstrated   thus long-term ability to
                         bioactive artificial   animal                 (extrusion)   seeded with cells                                     grafts were also             testing; electron   using a photosensitive GelMA hydrogel to   withstand immune response
                         auricular cartilage using                                                                                         taken from mice              microscopy    allow chondrocytes to bind to a customized   was not tested.
                         chondrocyte-laden GelMA                                                                                                                                      auricular scaffold.
                         and PLA for auricle                                                                                                                                        •  A biologic auricle with a PLA material as
                         reconstruction.                                                                                                                                              the inner core for support was constructed.
                                                                                                                                                                                      This not only provides mechanical support
                                                                                                                                                                                      for cartilage regeneration for morphological
                                                                                                                                                                                      maintenance in vitro and in vivo, but also
                                                                                                                                                                                      allows the ester bonds of PLA to be slowly
                                                                                                                                                                                      hydrolyzed, providing sufficient time for the
                                                                                                                                                                                      engineered cartilage to mature and acquire
                                                                                                                                                                                      mechanical properties while gradually
                                                                                                                                                                                      replacing the degrading PLA scaffold.












            Volume 9 Issue 6 (2023)                        288                        https://doi.org/10.36922/ijb.0898
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