Microneedle patches have received much interest in the last two decades as drug/vaccine delivery or fluid sampling systems for diagnostic and monitoring purposes. Microneedles are manufactured using a variety of additive and subtractive micromanufacturing techniques. In the last decade, much attention has been paid to using additive manufacturing techniques in both research and industry, such as 3D printing, fused deposition modeling, inkjet printing, and two-photon polymerization (2PP), with 2PP being the most flexible method for the fabrication of microneedle arrays. 2PP is one of the most versatile and precise additive manufacturing processes, which enables the fabrication of arbitrary three-dimensional (3D) prototypes directly from computer-aided-design (CAD) models with a resolution down to 100 nm. Due to its unprecedented flexibility and high spatial resolution, the use of this technology has been widespread for the fabrication of bio-microdevices and bio-nanodevices such as microneedles and microfluidic devices. This is a pioneering transformative technology that facilitates the fabrication of complex miniaturized structures that cannot be fabricated with established multistep manufacturing methods such as injection molding, photolithography, and etching. Thus, microstructures are designed according to structural and fluid dynamics considerations rather than the manufacturing constraints imposed by methods such as machining or etching processes. This article presents the fundamentals of 2PP and the recent development of microneedle array fabrication through 2PP as a precise and unique method for the manufacture of microstructures, which may overcome the shortcomings of conventional manufacturing processes.

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High-resolution two-photon polymerization: the most versatile technique for the fabrication of microneedle arrays.

Novel 3D-printed hollow microneedles facilitate safe, reliable, and informative sampling of perilymph from guinea pigs

https://link.springer.com/content/pdf/10.1186/s43094-020-00176-1.pdf

Emerging era of microneedle array for pharmaceutical and biomedical applications: recent advances and toxicological perspectives

The ongoing search for biodegradable and biocompatible microneedles (MNs) that are strong enough to penetrate skin barriers, easy to prepare, and can be translated for clinical use continues. As such, this review paper is focused upon discussing the key points (e.g., choice polymeric MNs) for the translation of MNs from laboratory to clinical practice. The review reveals that polymers are most appropriately used for dissolvable and swellable MNs due to their wide range of tunable properties and that natural polymers are an ideal material choice as they structurally mimic native cellular environments. It has also been concluded that natural and synthetic polymer combinations are useful as polymers usually lack mechanical strength, stability, or other desired properties for the fabrication and insertion of MNs. This review evaluates fabrication methods and materials choice, disease and health conditions, clinical challenges, and the future of MNs in public healthcare services, focusing on literature from the last decade.

https://www.mdpi.com/1999-4923/13/8/1132/pdf

Translation of Polymeric Microneedles for Treatment of Human Diseases: Recent Trends, Progress, and Challenges.

Investigations of two-photon polymerization of inorganic-organic hybrid materials initiated by femtosecond Ti:sapphire laser pulses are performed. First applications of this technique for the fabrication of three-dimensional microstructures and photonic crystals in inorganic-organic hybrid polymers with a structure size down to 200 nm and a periodicity of 450 nm are discussed.

Femtosecond Laser-Induced Two-Photon Polymerization of Inorganic-Organtic Hybrid Materials for Applications in Photonics

Drug delivery into the inner ear is a significant challenge due to its inaccessibility as a fluid-filled cavity within the temporal bone of the skull. The round window membrane (RWM) is the only delivery portal from the middle ear to the inner ear that does not require perforation of bone. Recent advances in microneedle fabrication enable the RWM to be perforated safely with polymeric microneedles as a means to enhance the rate of drug delivery from the middle ear to the inner ear. However, the polymeric material is not biocompatible and also lacks the strength of other materials. Herein we describe the design and development of gold-coated metallic microneedles suitable for RWM perforation. When developing microneedle technology for drug delivery, we considered three important general attributes: (1) high strength and ductility material, (2) high accuracy and precision of fabrication, and (3) broad design freedom. We developed a hybrid additive manufacturing method using two-photon lithography and electrochemical deposition to fabricate ultra-sharp gold-coated copper microneedles with these attributes. We refer to the microneedle fabrication methodology as two-photon templated electrodeposition (2PTE). We demonstrate the use of these microneedles by inducing a perforation with a minimal degree of trauma in a guinea pig RWM while the microneedle itself remains undamaged. Thus, this microneedle has the potential literally of opening the RWM for enhanced drug delivery into the inner ear. Finally, the 2PTE methodology can be applied to many different classes of microneedles for other drug delivery purposes as well the fabrication of small scale structures and devices for non-medical applications. Graphical Abstract Fully metallic ultra-sharp microneedle mounted at end of a 24-gauge stainless steel blunt syringe needle tip: (left) Size of microneedle shown relative to date stamp on U.S. one-cent coin; (right) Perforation through guinea pig round window membrane introduced with microneedle.

Amber M Parker

Papers

Drug delivery device for the inner ear: ultra-sharp fully metallic microneedles