Recent advances and perspectives of MicroNeedles for biomedical applications

Abstract

Microneedles (MN) technology has emerged as a transformative tool within the biomedical field, offering innovative solutions to challenges in drug delivery, diagnostics, and therapeutic applications. This review article provides an in-depth exploration of the diverse perspectives and applications of MNs, shedding light on their pivotal role in shaping the future of biomedical research and clinical practice. It begins by elucidating the fundamental principles of MNs: design, fabrication techniques, and materials, highlighting their capacity for minimally invasive access to the skin and underlying tissues. These attributes have driven advancements in transdermal drug delivery, facilitating precise and controlled administration of therapeutics, vaccines, and biologics, thus improving patient compliance and treatment outcomes. Furthermore, this review investigates the growing range of applications for MNs, including biomarker extraction, interstitial fluid (ISF) analysis, and continuous glucose monitoring. MNs enable real-time and minimally invasive monitoring of biochemical markers and have the potential to revolutionize disease diagnostics, personalized medicine, and wellness monitoring. Their compatibility with microfluidic systems further enhances their potential for point-of-care testing. This review serves as a comprehensive guide, highlighting the breadth of opportunities and challenges in leveraging MNs to improve healthcare outcomes and emphasizing the need for continued research and development in this dynamic field.

Keywords: Drug delivery; Fluid Extraction; MicroNeedles; Microfabrication; Microfluidic Devices.

Fig. 1

Examples of MNs types. A. SMN adapted from Hamzah et al. (2012). B. CMN adapted from Chen et al. (2015). C. HMN adapted from Davis et al. (2005). D. DMN adapted from Yang et al. (2021). E. HfMN adapted from Turner et al. (2023). F. PMNs adapted from Sadeqi et al. (2022)

Fig. 2

Fabrication methods to produce MNs. A) 3D printing adapted from Krieger et al. (2019); B) Micromilling adapted from Bediz et al. (2014); C) Etching adapted from Tang et al. ; D) Micro-moulding adapted from Yi et al. (2021); E) Laser ablation adapted from Aoyagi (2007); and F) Injection moulding process adapted from Evens et al. (2020)

Fig. 3

Schematic representation of MN applications in biomedical engineering

Fig. 4

A. SEM images showing the different MN shapes (flat (control) (A.1), hypodermic (A.2), pencil (A.3), triangular (A.4), and lancet (A.5)) used in this study (L500, W400, T500), along with the skin prick test (SPT) needle for comparison (A.6). Scale bars represent 1 mm. Adapted from Bisgaard et al. (2023) B. Morphology of the fabricated drug-loaded MNs. (B.1) Overall and (B.2) enlarged view of Rhodamine B-loaded MNs. Scale bars represent 1 mm. Adapted from Chen et al. (2023) C. Schematic of the MN patch-assisted delivery of aPD1 for skin cancer treatment. Schematic of the aPD1 delivered by an MN patch loaded with physiologically self-dissociated NPs with GOx/CAT enzymatic system immobilized inside the NPs by double-emulsion method, the enzyme-mediated conversion of blood glucose to gluconic acid promotes the sustained dissociation of NPs, subsequently leading to the release of aPD1. Adapted from Wang et al. (2016)

Fig. 5

A. In vitro swelling and fluid uptake by the obtained MNs using an agarose model system, adapted from Fonseca et al. (2020). B. Morphology of the fabricated drug-loaded MNs. MNs are functionalized with bespoke peptide nucleic acid (PNA) probes (blue) which are covalently bound to an alginate hydrogel matrix via a photocleavable linker (PCL, yellow), adapted from Ren et al. (2018). C. Schematic view of annular microneedles array (MNA) dry electrode and the principle of recording EEG on hairy scalp, adapted from Maia et al. . D. EEG signals recorded by the Ag/AgCl electrode, Fixed MNA and flexible parylene-based MNA under: (1) the eyes blinking, and (2) the open and closed eyes transition, adapted from Fonseca et al. (2020)

Fig. 6

A. Schematic showing the overall design used to test the therapeutic benefits of MN-CSCs on infarcted heart adapted from Tang et al. . B. A schematic representation of a microfluidics-based system to study mass transport phenomena in biosensors adapted from Trzebinski et al. (2012). C. Schematic of the proposed fluidic system combining a porous MN array and a microfluidic chip for minimally invasive and continuous ISF sampling adapted from Takeuchi et al. (2022). D. Chip design of a working chip adapted from Hileghem et al. (2023)