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

using TPP technology is shown in Figure 6A. In regions fabricated a microneedle tip with grooves, as shown in
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with larger outer diameters, the base of the microneedles Figure 6D. These grooves facilitate effective piercing of the
widens, a design incorporated to reduce fluid resistance. skin and guide the flow of the drug to desired locations.
Additionally, the lumen near the needle tip deviates from
the central axis and is bent to one side. These distinctive 4.3. Intricate functional 3D structures
features collectively improve the detection quality while Nature provides many inspirations for biomimetic
preserving the mechanical properties of the microneedle. microneedle designs. For example, the backward barbed
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Ren et al. manufactured microneedles with varying structure observed in the stinger of certain insects can
aspect ratios and hollow structures using 3D printing, be copied to enhance the adhesion and mechanical
and these microneedles were subsequently used to deliver properties of microneedles while reducing the insertion
drugs to mice with psoriasis. The experimental results force. 127,128 Traditional manufacturing methods, such as
showed an equivalent therapeutic efficacy with only 0.1 lithography and etching, and 3D laser lithography can
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times the oral dosage. Notably, traditional manufacturing create serrated microneedles. However, these methods
methods encounter significant challenges when it comes to entail complicated processes, specialized equipment, and
producing arrays of microneedles with varying parameters, full clean room environments.
highlighting a clear advantage of 3D printing in this regard. Although 3D printing excels in creating complex
In addition, conventional hollow microneedles solely rely structures, accomplishing unsupported microneedles
on the osmotic pressure to deliver drugs, with a single with backward barbs still presents a challenge. Four-
delivery mechanism and low efficiency. 122,123 Conversely, dimensional (4D) printing refers to a type of additive
3D printing enables the integration of hollow microneedles manufacturing technology that produces parts capable
with other microstructures for additional functionality. of morphing in shape, color, or even scent upon
Yeung et al. embedded hollow microneedles inside a environmental stimulation. This innovative approach
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3D spiral microfluidic structure to control the drug flow proposed by Han et al. enhances traditional 3D printing,
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rate at the inlet (Figure 6B). Combining microneedles making it possible to create complex structures without
with microfluidics opens new avenues for designing more relying on support structures (Figure 7). The microneedles
flexible and versatile transdermal drug delivery techniques. were 3D-printed with parallel barbs, and the crosslinking
Evidently, 3D printing provides simplified and intelligent density gradient generated during printing was exploited
solutions that are tailored to different disease requirements to transform the parallel barbs into backward-facing barbs
and human anatomical structures. upon stimulation. Experimental results verified that these
4.2. Diverse tip profile backward barbs significantly enhanced the tissue adhesion
The hollow structure discussed above refers to the internal to microneedles, achieving an impressive increase in
structure of microneedles, whereas the tip profile primarily adhesion of up to 18 folds compared to the traditional
refers to the external shape of the microneedles. The needles. This approach effectively overcomes the problem
microneedles tip profile is usually conical or pyramid- of microneedle detachment after insertion due to poor
shaped to facilitate skin piercing. With 3D printing, skin adhesion. The resulting highly stable microneedle has
additional features may be added to the tip profile to suit promising applications in long-term human monitoring
unique biomedical applications. In recent years, with the and controlled drug release.
rise in outbreaks such the one caused by coronavirus disease 4.4. Challenges
2019 (COVID-19), the need for rapid and comprehensive
vaccination coverage in the general population has become 4.4.1. Limited material selection
a public health priority. Li et al. drew inspiration from Although 3D printing enables impressive creativity and has
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the natural structure of mushrooms and used 3D printing straightforward operations, it has limitations in material
to reshape the traditional tip contour, forming a narrow selection, as compared to traditional manufacturing
transition with the substrate (Figure 6C). This biomimetic technologies. Some commonly used metals offer excellent
microneedle can easily degrade and release water-soluble biocompatibility and are widely used in the manufacturing
vaccines into the skin, greatly reducing the risk of infection of microneedles. 21,131,132 Commercially available CE-marked
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arising from the retention of microneedle tips in the microneedle roller predominantly uses titanium. Certain
skin. In addition, 3D printing has also enabled irregular carbon microneedles and ceramic microneedles created via
physiological lesions to be effectively microtargeted using micromechanical processes or micromolding also exhibit
microneedles with custom geometries, revolutionizing excellent biocompatibility. 134,135 Traditional manufacturing
the geometric adaptability of microtargeting irregular methods are compatible with a wide range of materials
physiological lesions. Xu et al. successfully designed and and can easily produce microneedle arrays with high
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Volume 10 Issue 4 (2024) 72 doi: 10.36922/ijb.1896