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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
             Zopf et al.    To determine the potential   In vitro;  Pigs  Direct printing  Laser sintering  Scaffold printed   Resembling   PCL  Chondrocytes   Chondrocytes   Histopathology  •  A novel image-based CAD/CAM 3D printing   Implantation into the pigs
             (2014)  [52]  of an integrated, image-  in vivo                         first and then   pinna; other                         were isolated from   were seeded into      process in the production of bioresorbable PCL  was only to demonstrate
                         based CAD and 3D    animal                                  seeded with cells  shape                              harvested porcine   the auricular PCL      scaffolds with a defined porous architecture for  appearance, so long-term in
                         printing approach to                                                                                              auricular cartilage  scaffolds using a     cartilaginous frameworks was introduced. The   vivo performance was not
                         engineer scaffolds for head                                                                                                     type I collagen gel.         technique utilized 3D printing for auricular   studied.
                         and neck cartilaginous                                                                                                          The cell suspension          and nasal scaffold production and control of
                         reconstruction for                                                                                                              was pipetted into            the pore architecture.
                         auricular and nasal                                                                                                             the PCL scaffolds,         •  The surgical implantation of scaffolds was
                         reconstruction.                                                                                                                 and the constructs           performed with ease, and scaffold porosity
                                                                                                                                                         were placed in an            allowed for the versatility and ease of suture
                                                                                                                                                         incubator (37°C,             placement. The PCL material maintained
                                                                                                                                                         5% CO ) for 30               excellent foundational support and appearance
                                                                                                                                                              2
                                                                                                                                                         minutes for gelation         when implanted in subcutaneous tissue.
                                                                                                                                                         to occur.                  •  The PCL scaffolds all demonstrated
                                                                                                                                                                                      histologically native-appearing cartilage
                                                                                                                                                                                      growth. However, the scaffolds had not
                                                                                                                                                                                      reached complete confluent cartilage coverage
                                                                                                                                                                                      after two months in vitro.
             Zopf et al.    To determine the effect   In vitro;  Athymic   Direct printing  Laser sintering   Scaffold printed   Resembling   PCL  Porcine auricular   Chondrocytes   Histopathology  •  Auricular constructs with two micropore   •  Short time in vivo
             (2018)  [54]  of auricular scaffold   in vivo   rodents   powder 3D printer  first and then   pinna                           cartilage     seeded into the              architectures were rapidly manufactured with   (4 weeks)
                         microarchitecture on   animal                               seeded with cells                                     chondrocytes  auricular PCL                high-fidelity anatomic appearance.  •  No mechanical testing of
                         chondrogenic potential in                                                                                                       scaffolds using a          •  Subcutaneous implantation of the scaffolds   scaffold
                         an in vivo animal model.                                                                                                        type I collagen/             resulted in excellent external appearance of   •  Study size unstated
                                                                                                                                                         HA composite gel.            both anterior and posterior auricular surfaces.
                                                                                                                                                         Seeded constructs          •  Comparing two different microporous
                                                                                                                                                         were cultured in             scaffold architectures demonstrated the
                                                                                                                                                         sterile, dynamic             importance of scaffold design in optimizing
                                                                                                                                                         conditions with              auricular cartilage growth.
                                                                                                                                                         incubation at 37°C,        •  Results suggest that a defined arrangement of
                                                                                                                                                         5% CO . After 4              spherical pores yielded more robust auricular
                                                                                                                                                              2
                                                                                                                                                         weeks of in vitro            tissue growth.
                                                                                                                                                         culture, they were         •  The creation of spherical micropores within
                                                                                                                                                         implanted into               the scaffold architecture appears to impart
                                                                                                                                                         rodents.                     greater chondrogenicity to the bioscaffold.
             Apelgren et al.   To evaluate if an integrated   In vivo   Rat  Direct printing  Extrusion 3D   Cells in bioink +   Other shape  Bioink  Human bone   After printing,   Histopathology  •  3D-bioprinted cartilage that has been allowed  •  Since rodents heal by
             (2018)  [3]  3D bioprinted cartilage   animal             bioprinter using   scaffold printed                                 marrow–derived   constructs were           to integrate in vivo is a sufficient base for a   withering, they may
                         construct has the capacity                    nano-fibrillated   together                                         mesenchymal stem  crosslinked with         full-thickness skin graft.       not be the ideal model
                         to serve as a bed for a full-                 cellulose/alginate                                                  cells & human   100 mM CaCl  for         •  Transplanted skin survived subcutaneously in   for studying the human
                                                                                                                                                                  2
                         thickness skin graft.                         bioink                                                              nasal chondrocytes  5 minutes in 37°C.     all the 20 surviving animals.    healing process in all
                                                                                                                                                         The constructs             •  No necrosis was observed. There were no   aspects.
                                                                                                                                                         were washed                  macroscopic signs of complications.  •  Moreover, rodents’
                                                                                                                                                         with a balanced            •  However, lymphocytic infiltration was   skin lacks apocrine
                                                                                                                                                         salt solution.               observed as a sign of inflammatory activity.  sweat glands and is
                                                                                                                                                         The printed                •  The majority of the chondrocytes did not   proportionally much
                                                                                                                                                         constructs were              survive (speculated to be due to diffusion   thinner than humans’
                                                                                                                                                         then immediately             limit).                          and has an additional
                                                                                                                                                         implanted                                                     muscle layer that makes
                                                                                                                                                         subcutaneously into                                           the comparisons difficult.
                                                                                                                                                         the mice.                                                   •  Short study time. The
                                                                                                                                                                                                                       long-term outcome of
                                                                                                                                                                                                                       shape stability, elastic
                                                                                                                                                                                                                       features, and tissue
                                                                                                                                                                                                                       integrity are crucial
                                                                                                                                                                                                                       factors that have to be
                                                                                                                                                                                                                       addressed in further
                                                                                                                                                                                                                       studies.



            Volume 9 Issue 6 (2023)                        292                        https://doi.org/10.36922/ijb.0898
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