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International Journal of Bioprinting                                Progress in bioprinted ear reconstruction




            technology is able to produce biocompatible scaffolds, which   search terms ((3D *print*) OR (additive manufacturing))
            can then be seeded with cells, or molds in which cartilage   AND ((auricle OR pinna OR ear) reconstruction) was
            can be cultivated into the desired shape. Several time-  conducted. The date  of the  last search  was 22 October
            consuming, multi-staged surgical steps (particularly rib   2022, but the search was not otherwise time-limited. The
            harvesting and shaping) could be bypassed [3,4] .  identified papers were  then  imported into  Covidence
               Before  engineering  a  substitute,  the  structure  of  the   software by Cochrane to conduct the review and follow
            auricle should be considered. At the most basic level,   the PRISMA standard. This process identified 202 original
            the structure is skin-covered cartilage with associated   studies.  After  duplicates  were  removed,  the  titles  and
            vasculature. The complex structure has distinct 3D parts   abstracts of 141 studies were screened. Seventy-three
            such as the helix, antihelix, concha, tragus, and lobule. It   studies were identified and underwent full-text review.
            is primarily composed of elastic cartilage covered by skin,   Of these, 27 studies were finally included (see Figure 2 for
            with a thin layer of connective tissue, the perichondrium,   workflow and inclusion and exclusion criteria).
            in between. Auricular cartilage comprises proteoglycans,   3D printing technologies (see  Figure 3) can aid and
            type II collagen, and an elastin network. Elastic fibers   enhance all of the existing reconstructive options. However,
            allow the ear to undergo extensive deformation, while   in this review, focus was placed on methods that could
            glycosaminoglycans (GAG) confer compressibility . Both   directly enhance surgical reconstruction by creating new
                                                    [9]
            properties, along with the complex shape, are important   implantable tissue-engineered personalized auricles for
            for  the  auricle’s  functionality  and,  unfortunately,  from  a   patients. Thus, additional studies on, for example, surgeons
            reconstructive perspective, are quite distinct from most   using costal cartilage models to practice autografting , to
                                                                                                         [17]
            other cartilages found in the human body .         create templates and guides  along which to cut , or to
                                                                                                      [18]
                                             [10]
                                                               plan the placement of bone-anchored prosthetic devices
                                                                                                           [19]
               Cartilage is an avascular and aneural tissue, and thus
            has a poor intrinsic self-repair capacity . However,   were excluded.
                                               [14]
            from a tissue engineering perspective, this avascularity is
            advantageous because if new elastic cartilage can be grown   3. Results
            or printed in vitro, a functioning vasculature does not have   In terms of design, all of the studies included (see Table 2)
            to be generated with it. Vessels around the engineered   were non-randomized experimental studies, except for the
            ear should be able to provide essential substances to   single landmark pilot clinical trial in human subjects by
            chondrocytes through diffusion .                   Zhou et al. . While the majority (n = 15) of the studies
                                     [15]
                                                                        [20]
               3D printing, as an additive manufacturing technique,   involved both in vitro and in vivo experiments (including
            fabricates physical constructs from digital models, layer by   the human study), some were purely in vitro (n = 6) and
            layer. This technology potentially facilitates the creation of   some purely in vivo (n = 6) animal studies.
            patient-specific, anatomically complex scaffolds. However,   Several animal models were used, with the majority
            limitations include time intensity for complex structures,   being in rodents (n = 16) but also in rabbits (n = 2), sheep
            potential discrepancies between the mechanical properties   (n = 1), pigs (n = 1), and goats (n = 1). It should be noted
            of printed materials and native tissues, and resolution   that  the  species into which the scaffold was  implanted
            constraints that may impact the replication of intricate   did not always match the donor tissue for the scaffold.
            auricular structures. Despite these challenges, 3D printing   For example, miniature pigs’ cartilage was inserted into
            presents a unique advantage in customization compared to   scaffolds that were eventually implanted into mice .
                                                                                                           [11]
            traditional fabrication methods [3,4,16] .         Several rodent model studies  noted that since rodents’
               At least theoretically, 3D-printed auricles promise   skin is different to human skin (lacking sweat glands,
            relative  ease  of  implantation,  anatomic  accuracy and   proportionally thinner, containing an additional muscle
            compatibility, and thus, excellent aesthetic results.  layer, and healing by withering), they may not be the ideal
                                                               animal model . On the other hand, sheep have similar
                                                                          [3]
            2. Methodology                                     fascial characteristics to humans . However, even then,
                                                                                         [21]
                                                               the physiology differs; thus, all studies noted that the goal
            This comprehensive literature review sought to investigate   was to establish human trials.
            the potential role of 3D printing in creating implantable
            constructs for reconstructive auricular surgery and how far   3.1. Direct versus indirect printing
            it is from being routinely implemented in clinical practice.
                                                               Five of the 27 included studies utilized indirect 3D
               In order to answer this, a broad systematic search in the   printing, in which a negative mold of the desired
            PubMed, Cochrane, and Web of Science databases using the   auricular shape is printed, meaning that the accurate and


            Volume 9 Issue 6 (2023)                        276                        https://doi.org/10.36922/ijb.0898
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