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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

