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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. 

Abstract Ingestible capsules have the potential to become an attractive alternative to traditional means of treating and detecting gastrointestinal (GI) disease. As device complexity increases, so too does the demand for more effective capsule packaging technologies to elegantly target specific GI locations. While pH-responsive coatings have been traditionally used for the passive targeting of specific GI regions, their application is limited due to the geometric restrictions imposed by standard coating methods. Dip, pan, and spray coating methods only enable the protection of microscale unsupported openings against the harsh GI environment. However, some emerging technologies have millimeter-scale components for performing functions such as sensing and drug delivery. To this end, we present the freestanding region-responsive bilayer (FRRB), a packaging technology for ingestible capsules that can be readily applied for various functional ingestible capsule components. The bilayer is composed of rigid polyethylene glycol (PEG) under a flexible pH-responsive Eudragit^®FL 30 D 55, which protects the contents of the capsule until it arrives in the targeted intestinal environment. The FRRB can be fabricated in a multitude of shapes that facilitate various functional packaging mechanisms, some of which are demonstrated here. In this paper, we characterize and validate the use of this technology in a simulated intestinal environment, confirming that the FRRB can be tuned for small intestinal release. We also show a case example where the FRRB is used to protect and expose a thermomechanical actuator for targeted drug delivery.