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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.
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3D‐Printed Microinjection Needle Arrays via a Hybrid DLP‐Direct Laser Writing Strategy
Abstract Microinjection protocols are ubiquitous throughout biomedical fields, with hollow microneedle arrays (MNAs) offering distinctive benefits in both research and clinical settings. Unfortunately, manufacturing‐associated barriers remain a critical impediment to emerging applications that demand high‐density arrays of hollow, high‐aspect‐ratio microneedles. To address such challenges, here, a hybrid additive manufacturing approach that combines digital light processing (DLP) 3D printing with “ex situ direct laser writing (esDLW)” is presented to enable new classes of MNAs for fluidic microinjections. Experimental results foresDLW‐based 3D printing of arrays of high‐aspect‐ratio microneedles—with 30 µm inner diameters, 50 µm outer diameters, and 550 µm heights, and arrayed with 100 µm needle‐to‐needle spacing—directly onto DLP‐printed capillaries reveal uncompromised fluidic integrity at the MNA‐capillary interface during microfluidic cyclic burst‐pressure testing for input pressures in excess of 250 kPa (n = 100 cycles). Ex vivo experiments perform using excised mouse brains reveal that the MNAs not only physically withstand penetration into and retraction from brain tissue but also yield effective and distributed microinjection of surrogate fluids and nanoparticle suspensions directly into the brains. In combination, the results suggest that the presented strategy for fabricating high‐aspect‐ratio, high‐density, hollow MNAs could hold unique promise for biomedical microinjection applications.
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- Award ID(s):
- 1943356
- PAR ID:
- 10395480
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Materials Technologies
- Volume:
- 8
- Issue:
- 5
- ISSN:
- 2365-709X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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