Cleanroom‐Free Fabrication of Microneedles for Multimodal Drug Delivery

Abstract

Microneedles have recently emerged as a powerful tool for minimally invasive drug delivery and body fluid sampling. To date, high‐resolution fabrication of microneedle arrays (MNAs) is mostly achieved by the utilization of sophisticated facilities and expertise. Particularly, hollow microneedles have usually been manufactured in cleanrooms out of silicon, resin, or metallic materials. Such strategies do not support the fabrication of microneedles from biocompatible/biodegradable materials and limit the capability of multimodal drug delivery for the controlled release of different therapeutics through a combination of injection and sustained diffusion. This study implements low‐cost 3D printers to fabricate relatively large needle arrays, followed by repeatable shrink‐molding of hydrogels to form high‐resolution molds for solid and hollow MNAs with controllable sizes. The developed strategy further enables modulating surface topography of MNAs to tailor their surface area and instantaneous wettability for controllable drug delivery and body fluid sampling. Hybrid gelatin methacryloyl (GelMA)/polyethylene glycol diacrylate (PEGDA) MNAs are fabricated using the developed strategy that can easily penetrate the skin and enable multimodal drug delivery. The proposed method holds promise for affordable, controllable, and scalable fabrication of MNAs by researchers and clinicians for controlled spatiotemporal administration of therapeutics and sample collection.

Design and fabrication of customizable microneedles enabled by 3D printing for biomedical applications

“…However, as these commercial resins were not originally formulated with biodegradability in mind, their functionality within biomedical applications may be limited. A number of studies have been conducted on formulation of biocompatible polymers for VP fabrication [ 34 , 82 , 83 ], allowing for the possibility to incorporate different properties into the printed parts.…”

“…This method involves printing a MN master template, which is used to make a negative mold. Hydrogel formulations are then casted into the negative mold to obtain dehydrated or shrunken MNs of the desired shape and size [ 83 , 101 ]. While preservation of the original structure and geometry during shrinking is a concern, Wang et al has showed that by attaching the base of the hydrogel MN to a polycarbonate film, uniform shrinking of the MN patch is achieved [ 101 ].…”

“…Interestingly, it was found that for both the conical and pyramidal MNs, contraction rate was higher in the Z-axis. In another study, Ghanbariamin et al further capitalized the shrink-molding method by first printing the MN master mold using SLA, subsequently using the shrunken hydrogel MNs to make negative molds and repeating this process several times to obtain MNs with increasingly higher resolution [ 83 ]. By varying the PEGDA hydrogel concentration, they could tune the rate of shrinkage, MN dimensions and mechanical properties.…”

Applications and prospects of microneedles in tumor drug delivery

“…124 3D printing has the advantages of high resolution printing, high printing speed and low printing cost, and it has become the preferred process for preparing hollow microneedles and microneedles with complex structures. Ghanbariamin et al 125 used low-cost 3D printing technology to prepare PEGDA/GelMA hydrogel microneedles with large sizes and then repeatedly contracted the hydrogel microneedles to prepare solid and hollow microneedles with controllable sizes.…”

Modern microelectronics and microfluidics on microneedles

“…The disadvantage is that it is too brittle to break easily like silicon. 42 According to the characteristics of different processing behaviors, there are thermoplastic and thermosetting resins. Commonly used are polyvinylpyrrolidone (PVP), polycarbonate (PC), epoxy resin and so on, among which PVP is a thermoplastic resin polymerized from ethylene.…”