In this focused progress review, the recent developments and trends of hydrogel‐forming microneedles (HFMs) and potential future directions are presented. Previously, microneedles (solid, hollow, coated, and dissolving microneedles) have primarily been used to enhance the effectiveness of transdermal drug delivery to facilitate a wide range of applications such as vaccinations and antibiotic delivery. However, the recent trend in microneedle development has resulted in microneedles formed from hydrogels which have the ability to offer transdermal drug delivery and, due to the hydrogel swelling nature, passively extract interstitial fluid from the skin, meaning they have the potential to be used for biocompatible minimally invasive monitoring devices. Thus, in this review, these recent trends are highlighted, which consolidate microneedle design considerations, hydrogel formulations, fabrication processes, applications of HFMs and the potential future opportunities for utilizing HFMs for personalized healthcare monitoring and treatment.
Conductive polymeric microneedle (MN) arrays as biointerface materials show promise for the minimally invasive monitoring of analytes in biodevices and wearables. There is increasing interest in microneedles as electrodes for biosensing, but efforts have been limited to metallic substrates, which lack biological stability and are associated with high manufacturing costs and laborious fabrication methods, which create translational barriers. In this work, additive manufacturing, which provides the user with design flexibility and upscale manufacturing, is employed to fabricate acrylic‐based microneedle devices. These microneedle devices are used as platforms to produce intrinsically‐conductive, polymer‐based surfaces based on polypyrrole (PPy) and poly(3,4‐ethylenedioxythiophene)‐poly(styrenesulfonate) (PEDOT:PSS). These entirely polymer‐based solid microneedle arrays act as dry conductive electrodes while omitting the requirement of a metallic seed layer. Two distinct coating methods of 3D‐printed solid microneedles, in situ polymerization and drop casting, enable conductive functionality. The microneedle arrays penetrate ex vivo porcine skin grafts without compromising conductivity or microneedle morphology and demonstrate coating durability over multiple penetration cycles. The non‐cytotoxic nature of the conductive microneedles is evaluated using human fibroblast cells. The proposed fabrication strategy offers a compelling approach to manufacturing polymer‐based conductive microneedle surfaces that can be further exploited as platforms for biosensing.
Hollow microneedle devices as a technology for interstitial fluid extraction show promise for the minimally invasive point‐of‐care detection of analytes. Despite increasing efforts toward on‐patch diagnostics, the use of hollow microneedles has been limited due to the complexity caused by integrating hollow microneedles with established point‐of‐care diagnostic techniques. Herein, a 3D printing method is utilized, to provide low‐cost manufacturing of custom‐designed hollow microneedle devices, allowing for easy integration with lateral flow assays for rapid and blood‐free diagnostics. Microneedle surface modification through PEGylation results in prolonged and enhanced hydrophilicity, enabling passive uptake of small volume samples (≈22.5 µL) and an enhanced shelf life. The hollow microneedle devices are deemed non‐cytotoxic to cell types found within the skin following short‐term and prolonged exposure in accordance with ISO10993. Furthermore, the devices demonstrate high mechanical strength and successfully penetrate porcine skin grafts without damaging the surrounding skin morphology. This work also demonstrates for the first time the use of hollow microneedles for the simultaneous detection, at clinically relevant concentrations, of C‐reactive protein (LoD = 10 µg mL−1) and procalcitonin (LoD = 1 ng mL−1), through porcine skin, ultimately demonstrating the beneficial use of manufactured 3D‐printed hollow microneedles towards low‐cost blood‐free diagnostics of inflammation markers.
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