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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
                                                                                                                                                                                    •  Chondrocytes grew well on the scaffold with
                                                                                                                                                                                      significant proliferation over time and very
                                                                                                                                                                                      few dead cells were observed at any of the
                                                                                                                                                                                      time points.
                                                                                                                                                                                    •  By 14 days, the chondrocytes had spread over
                                                                                                                                                                                      the entire scaffold.
                                                                                                                                                                                    •  Histological analysis performed at 6 weeks
                                                                                                                                                                                      showed that the ear-shaped constructs had
                                                                                                                                                                                      preliminarily formed cartilage-like tissue with
                                                                                                                                                                                      typical lacuna structure and strong positive
                                                                                                                                                                                      cartilage ECM staining.
                                                                                                                                                                                    •  However, the regenerated tissue showed a
                                                                                                                                                                                      hybrid structure, and some fibrous tissue
                                                                                                                                                                                      could be observed among the regenerated
                                                                                                                                                                                      cartilage regions.
                                                                                                                                                                                    •  At 12 weeks, the constructs formed mature
                                                                                                                                                                                      cartilage-like tissue with abundant lacuna
                                                                                                                                                                                      structure and more homogenous cartilage
                                                                                                                                                                                      ECM distribution, despite little fibrous tissue
                                                                                                                                                                                      could still be observed in small areas.
             Landau et al.   To develop a clinical-grade,  In vitro;  Mice  Indirect   BVOH mold   Scaffold printed   Resembling   PCL     Chondrocytes and   Mold was freeze-  Histopathology;  •  3D printing was used to create a PCL ear-  Small scale
             (2021)  [23]  3D-printed biodegradable   in vivo   printing  printing and   first and then   pinna; other                     MSCs          dried and washed   micro-CT scan;   shaped cartilage for transplants for microtia
                         auricle scaffold that formed  animal          subsequent    seeded with cells  shape                                            three times with   mechanical   patients.
                         stable, custom-made                           seeding                                                                           water, PBS and   testing; electron  •  The method can also be modified for use in
                         neocartilage implants.                                                                                                          then with a growth   microscopy  cases of complete lack of auricular cartilage,
                                                                                                                                                         medium to create             such as anotia and trauma, by integrating
                                                                                                                                                         a hydrophilic                costal cartilage cells.
                                                                                                                                                         environment for            •  The process is fast and simple for engineering
                                                                                                                                                         cell seeding.                a medical-grade auricle.
                                                                                                                                                                                    •  In vitro assessments showed a significant
                                                                                                                                                                                      advantage for the use of monoculture auricular
                                                                                                                                                                                      cartilage cells, but no significant differences
                                                                                                                                                                                      were observed in the constructs of various cell
                                                                                                                                                                                      types after implantation into mice.
                                                                                                                                                                                    •  No significant differences were observed in
                                                                                                                                                                                      lacuna development or collagen-2, elastin,
                                                                                                                                                                                      GAG, and collagen expression between the
                                                                                                                                                                                      two constructs, regardless of cultivation time.
             Yin et al.    To assess the feasibility and  In vitro;  Mice  Indirect   Resin 3D-printer   Scaffold printed   Resembling   A pair   Microtia   Cells seeded and   Histopathology;  •  All the cartilages generated by different   Large animal models are
             (2020)  [22]  in vivo long-term fate of   in vivo   printing  to create a set   first and then   pinna; other       of PGA/   chondrocytes  examined for cell   mechanical   patients’ cells were highly consistent in   needed
                         elastic cartilage regenerated  animal         of ear-shaped   seeded with cells  shape                  PLA layers              adhesion 24 h after   testing  both qualitative and quantitative data,
                         with an accurate human-                       negative molds.                                           and a PCL               incubation                   indicating high repeatability and stability of
                         ear shape using PCL inner                     A pair of PGA/                                            layer were                                           the construction technology of cartilages.
                         support-strengthened                          PLA layers (150                                           separately                                           Besides, PCL inner support had no inhibitory
                         biodegradable scaffold                        mg PGA fibers                                             pre-shaped                                           effect on cartilage regeneration, maturation,
                         and expanded MCs to                           each) and a PCL                                           by the                                               tissue integration, mechanical strength, and
                         identify factors that may                     layer were then                                           molds.                                               shape maintenance even after the complete
                         result in discrepant clinical                 separately pre-                                                                                                degradation of PCL.
                         outcomes.                                     shaped by the                                                                                                •  The implanted auricle framework could
                                                                       molds.                                                                                                         survive for a long time and successfully
                                                                                                                                                                                      regenerate mature and continuous cartilage
                                                                                                                                                                                      with an accurate human-ear shape.
                                                                                                                                                                                    •  After 12 weeks of in vitro culture and 12 months
                                                                                                                                                                                      of implantation in vivo, a porcelain white ear-
                                                                                                                                                                                      shaped cartilage with a shape similarity to the
                                                                                                                                                                                      original mold of 93.02% was formed.



            Volume 9 Issue 6 (2023)                        298                        https://doi.org/10.36922/ijb.0898
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