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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
             Visscher et al.   To develop a hydrogel-  In vitro  N/A  Direct printing  Extrusion  Cells in bioink +   Resembling   Bioink  Porcine ear   UV crosslinking   Histopathology;  •  A photo-crosslinkable cartilage-derived   In vitro only
             (2021)  [28]  based bioink that recreates                               scaffold printed   pinna; other                       cartilage     after printing  mechanical   ECM-based bioink was successfully developed   •  Large protein
                         the complex cartilage                                       together; scaffold   shape                                                         testing; other   for auricular cartilage reconstruction and   heterogeneity observed
                         microenvironment.                                           only                                                                               such as mass   supported the activity and maturation of   between samples in
                                                                                                                                                                        spectrometry   chondrocytes in bioprinted constructs.  the mass spectrometric
                                                                                                                                                                        proteome    •  Decellularized cartilage-derived ECM can be   analyses, which makes
                                                                                                                                                                        analysis      used for cell-based 3D bioprinting.  it difficult to draw a
                                                                                                                                                                                    •  The inclusion of gelatin, HA, and glycerol   specific conclusion
                                                                                                                                                                                      improved printability and initial structural   on effects of protein
                                                                                                                                                                                      integrity, while UV polymerization increased   abundance on growth
                                                                                                                                                                                      stiffness.
                                                                                                                                                                                    •  The stiffness of the gel may affect cell
                                                                                                                                                                                      behavior.
             Bhamare et al.   To synthesize pinna from   In vitro;  Rat  Direct printing  Extrusion  Cells in bioink +   Resembling   Bioink  Goat cartilage used  Ethylene oxide   Histopathology;  •  The ear had biodegradable properties despite   Small study in animals only
             (2021)  [26]  printable bioink. Ear pinna   in vivo                     scaffold printed   pinna                              in bioink     used to sterilize   ultrasound   containing polymers.
                         bioink was prepared from   animal                           together                                                            scaffold before   scan; micro-  •  Mechanical strength of 3D-printed pinna
                         xenogenic goat cartilage                                                                                                        implantation. It was  CT scan;   showed similar results like normal ear pinna.
                         by adding polymers and                                                                                                          trimmed into pieces  mechanical   •  Pinna was biocompatible (in ovo and in
                         optimized for 3D printing.                                                                                                      (10 mm in width),   testing  vivo) having newly developed chondrocytes,
                                                                                                                                                         and rinsed with              elastin fibers, progenitor cells of ECM after
                                                                                                                                                         saline containing            transplantation.
                                                                                                                                                         antibiotic solution.       •  Within 30 days, the transplanted 3D-printed
                                                                                                                                                                                      pinna regenerated chondrocytes, GAG,
                                                                                                                                                                                      elastin fibers, collagen, and retained its ECM.
                                                                                                                                                                                    •  The occurrence of angiogenesis after grafting
                                                                                                                                                                                      showed that the 3D-printed ear pinna was
                                                                                                                                                                                      accepted by the rat ear and had non-toxic
                                                                                                                                                                                      properties similar to those of a native ear pinna.
             Dong et al.   To determine whether   In vitro;  Rat  Direct printing  Extrusion  Scaffold printed   Other shape     PLA       Bovine auricular   Chondrocytes in   Histopathology  •  Scaffolds were fabricated using injection   Using bovine cells is a
             (2021)  [10]  3D-printed, biocompatible   in vivo                       first and then                                        chondrocytes  collagen hydrogels           molding to protect auricular cartilage   necessary step toward
                         scaffolds would     animal                                  seeded with cells                                                   were added to the            constructs from external compression and   eventually using human
                         “protect” maturing                                                                                                              printed constructs.          intrinsic contractile forces, resulting in   cells to produce clinically
                         hydrogel constructs                                                                                                             Cell-loaded                  significant reduction of contraction and   translatable results. Using
                         from contraction and                                                                                                            constructs were              preservation of complex topography.  a rodent model is limiting
                         topography distortion.                                                                                                          cultured in DMEM           •  Injection molding allows for the creation of a   because the loose nature
                                                                                                                                                         overnight before             more fully interconnected porous network and  of rodent skin does not
                                                                                                                                                         implantation.                is particularly effective for quickly producing   accurately replicate
                                                                                                                                                                                      homogenous volumes with high accuracy.  the compressive forces
                                                                                                                                                                                    •  Mechanically attaching a cell-seeded collagen   experienced by scaffolds
                                                                                                                                                                                      construct to an external structure helps   under human auricular or
                                                                                                                                                                                      maintain shape retention during extended   scalp skin.
                                                                                                                                                                                      culture in vitro.
                                                                                                                                                                                    •  Larger (12-mm wide) porous PLA discs
                                                                                                                                                                                      featuring a ridge on the surface were designed
                                                                                                                                                                                      to simulate the shape of the helical rim and
                                                                                                                                                                                      compensate for anticipated contraction,
                                                                                                                                                                                      blunting, and distortion. After 3 months
                                                                                                                                                                                      in vivo, the helical rim feature was better
                                                                                                                                                                                      preserved in the injection molded (SInj) and
                                                                                                                                                                                      scaffolded (S) groups compared to the naked
                                                                                                                                                                                      (N) group, which lost the rim feature and
                                                                                                                                                                                      became a flat disc of cartilage.
                                                                                                                                                                                    •  The presence of an external PLA scaffold did
                                                                                                                                                                                      not hinder the formation of healthy cartilage
                                                                                                                                                                                      within the constructs.




            Volume 9 Issue 6 (2023)                        284                        https://doi.org/10.36922/ijb.0898
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