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Microneedles are highly sought after for medicinal and cosmetic applications. However, the current manufacturing process for microneedles remains complicated, hindering its applicability to a broader variety of applications. As diffraction lithography has been recently reported as a simple method for fabricating solid microneedles, this paper presents the experimental validation of the use of ultraviolet light diffraction to control the liquid-to-solid transition of photosensitive resin to define the microneedle shape. The shapes of the resultant microneedles were investigated utilizing the primary experimental parameters including the photopattern size, ultraviolet light intensity, and the exposure time. Our fabrication results indicated that the fabricated microneedles became taller and larger in general when the experimental parameters were increased. Additionally, our investigation revealed four unique crosslinked resin morphologies during the first growth of the microneedle: microlens, first harmonic, first bell-tip, and second harmonic shapes. Additionally, by tilting the light exposure direction, a novel inclined microneedle array was fabricated for the first time. The fabricated microneedles were characterized with skin insertion and force-displacement tests. This experimental study enables the shapes and mechanical properties of the microneedles to be predicted in advance for mass production and wide practical use for biomedical or cosmetic applications.
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Laser Fabrication of Polymeric Microneedles for Transdermal Drug Delivery
Microneedles provide a transdermal pathway for drug delivery, cosmetic infusion, vaccine administration, and disease diagnostics. Microneedle fabrication relies on the interplay of several variables which include design parameters, material properties, and processing conditions. In this research, our group explores the effect of design parameters and process variables for laser ablation of microneedles within a Polymethyl methacrylate (PMMA) mold. An Ytterbium laser (200W) was utilized to study the effect of five inputs factors (laser power, pulse width, number of repetitions, laser waveform, and interval time between laser pulses) on two output factors (diameter and height) of the fabricated microneedles. Polydimethylsiloxane (PDMS) polymer was cast within the PMMA microneedle mold. Scanning electron microscopy (SEM) was employed to image topographical features of the microneedles. Further, mechanical testing of the microneedles was conducted to evaluate the buckling load and deformation behavior of the microneedle array. A 20W pulse laser with trapezoidal waveform resulted in optimal microneedle topography with an aspect ratio of 1.2. ANOVA results (α = 0.05) depicted that laser power and number of repetitions were significant factors determining the geometrical features of the microneedle array. This research establishes a framework for the design and manufacturing of customized microneedles for precision medicine.
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- Award ID(s):
- 1663128
- PAR ID:
- 10297495
- Date Published:
- Journal Name:
- Proceedings of the 2021 IISE Annual Conference
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Microneedle arrays show many advantages in drug delivery applications due to their convenience and reduced risk of infection. Compared to other microscale manufacturing methods, 3D printing easily overcomes challenges in the fabrication of microneedles with complex geometric shapes and multifunctional performance. However, due to material characteristics and limitations on printing capability, there are still bottlenecks to overcome for 3D printed microneedles to achieve the mechanical performance needed for various clinical applications. The hierarchical structures in limpet teeth, which are extraordinarily strong, result from aligned fibers of mineralized tissue and protein‐based polymer reinforced frameworks. These structures provide design inspiration for mechanically reinforced biomedical microneedles. Here, a bioinspired microneedle array is fabricated using magnetic field‐assisted 3D printing (MF‐3DP). Micro‐bundles of aligned iron oxide nanoparticles (aIOs) are encapsulated by polymer matrix during the printing process. A bioinspired 3D‐printed painless microneedle array is fabricated, and suitability of this microneedle patch for drug delivery during long‐term wear is demonstrated. The results reported here provide insights into how the geometrical morphology of microneedles can be optimized for the painless drug delivery in clinical trials.more » « less
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Microneedles are micron-sized devices that are used for the transdermal administration of a wide range of active pharmaceutics substances with minimally invasive pain. In the past decade, various additive manufacturing technologies have been used for the fabrication of microneedles; however, they have limitations due to material compatibility and bioavailability and are time-consuming and expensive processes. Additive manufacturing (AM), which is popularly known as 3D-printing, is an innovative technology that builds three-dimensional solid objects (3D). This article provides a comprehensive review of the different 3D-printing technologies that have the potential to revolutionize the manufacturing of microneedles. The application of 3D-printed microneedles in various fields, such as drug delivery, vaccine delivery, cosmetics, therapy, tissue engineering, and diagnostics, are presented. This review also enumerates the challenges that are posed by the 3D-printing technologies, including the manufacturing cost, which limits its viability for large-scale production, the compatibility of the microneedle-based materials with human cells, and concerns around the efficient administration of large dosages of loaded microneedles. Furthermore, the optimization of microneedle design parameters and features for the best printing outcomes is of paramount interest. The Food and Drug Administration (FDA) regulatory guidelines relating to the safe use of microneedle devices are outlined. Finally, this review delineates the implementation of futuristic technologies, such as artificial intelligence algorithms, for 3D-printed microneedles and 4D-printing capabilities.more » « less
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Microinjection protocols that involve using a hollow, high-aspect-ratio microneedle to deliver foreign material (e.g., cells, DNA, viruses, and micro/nanoparticles) into biological targets (e.g., embryos, tissues, and organisms) are essential to diverse biomedical applications in both research and clinical settings. A key deficit of such protocols, however, is that standard microneedle architectures are inherently susceptible to clogging-induced failure modes, which can diminish experimental rigor and lead to failed microinjections. Additive manufacturing (or “three-dimensional (3D) printing”) strategies based on “Two-Photon Direct Laser Writing (DLW)” offer a promising route to address clogging failure phenomena by rearchitecting the needle tip, yet achieving 3D-printed microneedles with the mechanical strength necessary to penetrate into biological targets (e.g., embryos) has remained a critical barrier to efficacy. To overcome this barrier, here we harness a recently reported polyhedral oligomeric silsequioxane (POSS) photomaterial to DLW-print fused silica glass high-aspect-ratio microinjection needles with enhanced mechanical strength. Experimental results for POSS-based 3D-nanoprinted microneedles with inner and outer diameters of 10 μm and 15 μm, respectively, and heights ranging from 500–750 μm revealed that the needles not only enabled successful puncture and penetration into early-stage zebrafish embryos, but also significantly reduced the magnitude of undesired deformations to the embryos during needle puncture and penetration from 61.0±12.1 μm for standard glass-pulled control microneedles to 42.4±11.5 μm for the POSS-enabled 3D microneedles (p < 0.01). In combination, these results suggest that wide-ranging biomedical fields could benefit from the presented 3D microinjection needles.more » « less
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