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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
                                                                                                                                                                                    •  The PCL support was completely covered by
                                                                                                                                                                                      the regenerated cartilage with satisfactory
                                                                                                                                                                                      integration.
                                                                                                                                                                                    •  Tissue-engineered cartilage shows typical
                                                                                                                                                                                      phenotype of mature elastic cartilage similar
                                                                                                                                                                                      to microtia ear tissue with typical lacuna
                                                                                                                                                                                      structures and strong positive staining of
                                                                                                                                                                                      safranin O, type Il collagen, and Verhoeff-van
                                                                                                                                                                                      Gieson (EVG).
             Liao et al.    To reconstruct the auricle   In vivo   Rabbit  Indirect   Molds printed   Scaffold only  Resembling   Other:   Diced cartilage   PRP was mixed   Histopathology;  •  The porous, hollow, poly-amide auricular   The synthetic, non-
             (2019)  [24]  using a porous, hollow,   animal  printing  by SLS                      pinna                         PGLA      graft         with diced cartilage  mechanical   mold prepared by 3D printing and packed   biodegradable poly-amide
                         3D-printed mold and                                                                                     membrane                and sodium citrate,   testing  with diced cartilages and PRP graft showed   induced a cystic-like
                         autologous diced cartilage                                                                                                      and this paste was           appropriate biomechanical properties and   reaction around the
                         mixed with PRP                                                                                                                  inserted into the            maintained it shape, with good chondrocyte   implant. It is unclear
                                                                                                                                                         printed porous               viability and the production of a cartilaginous  whether this translates in
                                                                                                                                                         scaffold                     extracellular matrix           the clinical setting to the
                                                                                                                                                                                    •  It was found that mixing the cartilage   formation of a seroma or a
                                                                                                                                                                                      with a PRP improved the viability of the   chronic granuloma/foreign
                                                                                                                                                                                      diced cartilage when wrapped in a PLGA   body reaction. Another
                                                                                                                                                                                      membrane.                      limitation of this work is
                                                                                                                                                                                    •  At 4 months, the diced cartilage pieces within   that we did not explore the
                                                                                                                                                                                      the mold had fused, and the gross appearance  possibility of using other
                                                                                                                                                                                      was similar in shape to an auricle.  biodegradable materials,
                                                                                                                                                                                    •  No complications (e.g., hematoma, seroma, or  such as PLGA for the
                                                                                                                                                                                      infection) were observed at the implantation   hollow auricle mold.
                                                                                                                                                                                      site during the postoperative period.
                                                                                                                                                                                    •  The results of histological staining showed
                                                                                                                                                                                      that the diced cartilages after shaping retained
                                                                                                                                                                                      viable chondrocytes and a complete ECM,
                                                                                                                                                                                      with positive staining for GAGs, collagen
                                                                                                                                                                                      fibers, and elastic fibers, which determine the
                                                                                                                                                                                      biomechanical properties of the cartilage.
             Zhou et al.   To clinically apply tissue-  In vitro;  N/A  Indirect   A resin model was  Scaffold printed   Resembling   PGA,    Isolated microtia   Expanded microtia   Histopathology;  •  It is possible to successfully design, fabricate,   •  Small sample of only 5
             (2018)  [20]  engineered and 3D-printed  in vivo   printing  generated through  first and then   pinna              PLA, and   chondrocytes  cartilage cells were   mechanical   and re-generate patient-specific external ears   patients
                         ear-shaped cartilage to   human               3D printing. This   seeded with cells                     PCL were                evenly dropped   testing; electron   (in human subjects).   •  Longest follow-up of
                         human subjects for the first  trial           resin ear model                                           processed               onto the PGA/PLA   microscopy;   •  12 weeks of tissue expansion were used to   only 2.5 years (other
                         time.                                         was used to cast                                          into the ear            layer of the scaffold,  other:   create a large enough skin flap. A facial flap   cases 2–18 months):
                                                                       a pair of negative                                        scaffold                followed by 5-h   photography   was used to cover the back and the helix rim   unknown result after
                                                                       molds.                                                                            incubation at 37°C,  and visual   of the engineered ear graft, which not only   complete degradation of
                                                                                                                                                         5% CO The      inspection of   provided sufficient blood supply, but also   PCL scaffold (takes 2–4
                                                                                                                                                              2.
                                                                                                                                                         construct was   final clinical   protected the graft from extrusion.  years)
                                                                                                                                                         then cultured in   result at 1, 2, 3,   •  Subsequent surgeries (scar revision) were   •  Only pilot study: further
                                                                                                                                                         chondrogenic   6, 9, 12, 18, 24,   conducted for removing the pedicle of skin   work necessary to
                                                                                                                                                         medium for 12   and 30 months   flap at 6 months and repairing scar at 18   translate this into routine
                                                                                                                                                         weeks.         post-surgery to   months, which allowed for tissue biopsies of   clinical practices
                                                                                                                                                                        record swelling,   the implanted ear framework.  •  Optimization and
                                                                                                                                                                        inflammation   •  After two weeks, the initial postoperative   standardization in
                                                                                                                                                                        signs, and shape   edema slowly reduced, and the shape of the   scaffold fabrication, cell
                                                                                                                                                                        recovery.     reconstructed ear, as well as the color of the   expansion, and in vitro
                                                                                                                                                                        MRI (1.5T) to   covered skin, gradually recovered. Within 6   cartilage engineering,
                                                                                                                                                                        trace cartilage   months post-implantation, only the basic ear   surgical procedures are
                                                                                                                                                                        regeneration   contour was observed, while key auricular   still required.
                                                                                                                                                                        and PCL core   structures, such as helix, triangular fossa,   •  Single center
                                                                                                                                                                        degradation   anti-helix, and cavum conchae, became
                                                                                                                                                                                      gradually distinct after 9 months.




            Volume 9 Issue 6 (2023)                        300                        https://doi.org/10.36922/ijb.0898
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