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International Journal of Bioprinting                          Unique characteristics of 3D-printed microneedles




            performance of microneedles. Heat treatment is a basic   have resorted to the utilization of cadaver skin, a practice
            method for enhancing the hardness of light cured resins,   not without ethical and moral implications. Conversely,
            but it adds additional processing complexity and may   animal skin, such as pig skin and mouse skin, are
            not produce optimal results. Consequently, balancing the   extensively used in microneedle experimentation. Among
            ratios of multiple materials poses a considerable challenge   commonly utilized animal skin models, pig skin bears the
            for 3D printing microneedles.                      most structural resemblance to human skin, making it the
                                                               most prevalent experimental model in clinical research.
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               Metal 3D printing is typically available via PBF
            techniques.  However,  the  resolution  of  commercially   Despite the 10-fold difference in thickness compared to
                                                               human skin,  mouse skin offers advantages such as the
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            available PBF metal printers is insufficient for microneedle   ability to provide an intuitive readout of drug delivery
            manufacturing due to limitations on the minimum powder   efficiency, biocompatibility, stability, and other microneedle
            size. Although several metal 3D printing techniques 3,140    performance metrics. Rabbit skin and chicken breast have
            have been reported to achieve micron or even submicron   also been used as models to assess microneedle puncture
            resolution, they are still in the early development stage and   capabilities due to their toughness akin to human skin. 130,148
            hence not widely accessible. Furthermore, the throughput   However, animal skin has certain limitations, such as high
            of these micrometal 3D printing techniques is typically   shape variability, the need for pre-treatment, and elastic
            too low for microneedle fabrication. Therefore, there   properties not comparable to human skin.
            is no viable solution for the manufacturing of metal
            microneedles via 3D printing.                         Artificial skin can simulate the mechanical
                                                               properties and/or permeability of human skin, and can
            4.4.2. Low manufacturing throughput                be used as alternative to animal skin. Paraffin film,
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            Another drawback of 3D printing is its relatively slow   polydimethylsiloxane (PDMS)  films, and alginate
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            manufacturing speed, particularly when striving for high   hydrogel  have been adopted for this purpose. Artificial
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            resolution. McKee et al.  reported that 12 h are needed to   skin offers the advantages of standardization and
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            manufacture a 7 × 7 array of conical microneedles. The novel   reproducibility, thereby reducing experimental variations.
            SOPL technology offers unprecedented manufacturing   Their use is also compliant with ethical standards.
            speed, enabling the fabrication of microneedle arrays in as   Nonetheless, non-active artificial skins cannot mimic
            short as 5 s,  even for array containing microneedles with   physiological responses such as skin irritation, allergy, and
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            different shapes or hollow structures. It also eliminates   bleeding.  Despite these limitations and the lack practical
            stepped structures but requires materials with certain   data, artificial skin models can be used to set benchmark for
            degree of transparency. MRDL can also produce smooth-  microneedle evaluation. Although the problem concerning
            surfaced microneedles in a few seconds, but this method   skin models is not exclusive to 3D-printed microneedles
            requires complex systems for producing and controlling   but rather a shared concern for all types of microneedles,
            the required magnetic field.  Nonetheless, SOPL and   its significance necessitates particular emphasis, thus
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            MRDL, while offering significant advantages in terms   warranting a detailed discussion in this section.
            speed, are not widely accessible 3D printing technologies
            and come with their own limitations.               5. Conclusion and outlook
               Traditional molding techniques, such as injection   This paper provides a concise overview of manufacturing
            molding,  hot press molding,  and solution casting,    methods, both traditional and additive, for microneedles. The
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            are prevailing methods for efficient large-scale microneedle   most promising applications for 3D-printed microneedles
            manufacturing. Consequently, achieving low-cost mass   were also presented. This review comprehensively analyzes
            production of microneedles using 3D printing  is hampered   the unique advantages and limitations of 3D-printed
            by its very low throughput.                        microneedles. Traditional manufacturing methods,
                                                               although inexpensive and scalable, have poor resolution and
            4.4.3. Lack of physiological models for testing    are severely constrained in the structures that can be made.
            3D-printed microneedles                            In contrast, 3D printing methods can create microneedles
            Currently, the majority of  microneedles studies are geared   with intricate 3D structures such as hollow interiors,
            toward transdermal drug delivery. To expedite the clinical   diverse tip profiles, and other biomimetic structures like
            integration and commercialization of microneedles,   barbs to enhance microneedle functionality. 3D printing
            sufficient high-quality experimental data acquired with skin   effectively addresses many of the significant longstanding
            models are imperative. Human skin is an ideal experimental   shortcomings of traditional manufacturing. Moreover, 3D
            model. However, it poses formidable challenge to secure   printing is heavily automated and requires less material
            sufficient human skin tissues.  In response, researchers   and fewer processes compared to traditional methods.
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            Volume 10 Issue 4 (2024)                        74                                doi: 10.36922/ijb.1896
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