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International Journal of Bioprinting                                Progress in bioprinted ear reconstruction






 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
 Brennan et al.   To evaluate the design   In vivo   Rats  Direct printing  Laser sintering   Scaffold only  Resembling   PCL  N/A  Sterilized by   Histopathology;  •  A 3D-printed bioscaffold was developed   H&E was used to assess
 (2021)  [4]  and initial performance of   animal  PCL with a   pinna  low-temperature   micro-CT scan;   for auricular reconstruction with a realistic   for vascularization.
 the auricular scaffold in a   mixture of 4%   ethylene oxide gas   mechanical   anatomic appearance that meets or exceeds   Quantification of
 preclinical animal model   hydroxyapatite   sterilization prior to  testing  the best outcomes of rib cartilage grafting  angiogenesis has inherent
 study. Our hypothesis was   (Plasma Biotal)   implantation  •  The shape of the construct was durable and   challenges based off how
 that the two-stage approach   where the HA                    did not experience contraction or distortion   the histology captures the
 would limit the overlying   serves primarily as               over the course of the experiment.  blood vessels and the lack
 soft tissue strain and thus   a flowing agent for           •  The scaffold demonstrated robust tissue   of specificity of H&E to
 result in lower rates of soft   powder spreading              ingrowth and angiogenesis, suggesting it could   stain vessels. So other stains
 tissue ulceration, necrosis,   during the laser               support the growth of cartilaginous tissue.  should be used.
 and related complications   sintering process               •  The technique resulted in unparalleled ear   Additional work is
 compared to the single-                                       appearance in vivo.            necessary to assess the
 stage reconstruction.                                       •  Ulceration was a problem in all the rats,   potential to cellularize the
                                                               regardless of single or two staging.  scaffold with the ultimate
                                                             •  Minor superficial ulcers occurred most   goal of gradual replacement
                                                               commonly at the lateral (86% of animals)   with a native cartilage
                                                               and superior (29% of animals) helix of the   matrix.
                                                               scaffold.
                                                             •  Promisingly, there were high rates of
                                                               improvement in ulceration over time with
                                                               only a quarter of models demonstrating
                                                               worsening in ulceration over the course of
                                                               experimentation. Bolstered by findings of
                                                               robust angiogenesis, the authors speculated
                                                               that the improvement in wound healing
                                                               was secondary to the angiogenesis and
                                                               transformation of a bare PCL scaffold to an
                                                               integrated, vascularized tissue implant.
                                                             •  The porous architecture design may improve
                                                               outcomes by reducing skin complications
                                                               and allowing increased tissue and vascular
                                                               ingrowth to enhance reconstruction and
                                                               accelerate healing of skin ulceration.
 Chang et al.   To analyze the use of highly  In vivo   Rat  Direct printing  Extrusion  Scaffold printed   Resembling   PCL  Porcine punch   All scaffolds were   Histopathology;  •  Vascularization was observed in both   No statistically significant
 (2020)  [47]  translatable 3D–printed   animal  first and then   pinna  biopsies inserted   sterilized with   micro-CT scan  unseeded and seeded scaffolds, indicating that  difference was observed
 auricular scaffolds with   seeded with cells  into scaffolds   ethylene oxide  non-autologous tissue implants do not inhibit  between cartilage-seeded
 and without novel cartilage   to facilitate   Prior to        vessel formation.              and unseeded scaffolds
 tissue inserts in a rodent   chondrocyte   implantation. Half   •  This technique is readily clinically translatable  in any category of
 model.             seeding       of the sample was            as it eliminates in vitro requirements and   ulceration. This may be
                                  cartilage-seeded,            accompanying regulatory burden.  due to the small sample
                                  with the other             •  The 3D-printed auricles with and without   size or the methods used
                                  unseeded.                    cartilage inserts were structurally similar to   to measure ulceration.
                                                               human ears and measurements remained   The use of additional
                                                               consistent.                    immunohistochemistry
                                                             •  There was no significant retraction or   might clarify whether
                                                               degradation of scaffolds during the   chondrocytes are present
                                                               experiment, suggesting resistance to   beyond the limits of the
                                                               contractile forces and sustained feasibility of   cartilage punch biopsy and
                                                               such implants.                 from which tissue they
                                                             •  Micro-CT imaging showed infiltration of soft   arise.
                                                               tissue into the pores of hybrid scaffolds.
                                                             •  Healing of ulceration was seen in both
                                                               conditions, with smaller rates of scaffold-
                                                               induced ulceration in cartilage-seeded
                                                               scaffolds.
                                                                                                         (Continued)



            Volume 9 Issue 6 (2023)                        295                        https://doi.org/10.36922/ijb.0898
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