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1. 3D Printing of Biodegradable Polymeric Microneedles for Transdermal Drug Delivery Applications

   https://doi.org/10.3390/pharmaceutics16020237  

   Aldawood, Faisal Khaled; Parupelli, Santosh Kumar; Andar, Abhay; Desai, Salil (February 2024, Pharmaceutics)

   Microneedle (MN) technology is an optimal choice for the delivery of drugs via the transdermal route, with a minimally invasive procedure. MN applications are varied from drug delivery, cosmetics, tissue engineering, vaccine delivery, and disease diagnostics. The MN is a biomedical device that offers many advantages including but not limited to a painless experience, being time-effective, and real-time sensing. This research implements additive manufacturing (AM) technology to fabricate MN arrays for advanced therapeutic applications. Stereolithography (SLA) was used to fabricate six MN designs with three aspect ratios. The MN array included conical-shaped 100 needles (10 × 10 needle) in each array. The microneedles were characterized using optical and scanning electron microscopy to evaluate the dimensional accuracy. Further, mechanical and insertion tests were performed to analyze the mechanical strength and skin penetration capabilities of the polymeric MN. MNs with higher aspect ratios had higher deformation characteristics suitable for penetration to deeper levels beyond the stratum corneum. MNs with both 0.3 mm and 0.4 mm base diameters displayed consistent force–displacement behavior during a skin-equivalent penetration test. This research establishes guidelines for fabricating polymeric MN for high-accuracy and low-cost 3D printing. 

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2. Micromolding of Amphotericin-B-Loaded Methoxyethylene–Maleic Anhydride Copolymer Microneedles

   https://doi.org/10.3390/pharmaceutics14081551  

   Azizi Machekposhti, Sina; Nguyen, Alexander K.; Vanderwal, Lyndsi; Stafslien, Shane; Narayan, Roger J. (August 2022, Pharmaceutics)

   Biocompatible and biodegradable materials have been used for fabricating polymeric microneedles to deliver therapeutic drug molecules through the skin. Microneedles have advantages over other drug delivery methods, such as low manufacturing cost, controlled drug release, and the reduction or absence of pain. The study examined the delivery of amphotericin B, an antifungal agent, using microneedles that were fabricated using a micromolding technique. The microneedle matrix was made from GantrezTM AN-119 BF, a benzene-free methyl vinyl ether/maleic anhydride copolymer. The GantrezTM AN-119 BF was mixed with water; after water evaporation, the polymer exhibited sufficient strength for microneedle fabrication. Molds cured at room temperature remained sharp and straight. SEM images showed straight and sharp needle tips; a confocal microscope was used to determine the height and tip diameter for the microneedles. Nanoindentation was used to obtain the hardness and Young’s modulus values of the polymer. Load–displacement testing was used to assess the failure force of the needles under compressive loading. These two mechanical tests confirmed the mechanical properties of the needles. In vitro studies validated the presence of amphotericin B in the needles and the antifungal properties of the needles. Amphotericin B GantrezTM microneedles fabricated in this study showed appropriate characteristics for clinical translation in terms of mechanical properties, sharpness, and antifungal properties. 

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3. 3D microfluidics via cyclic olefin polymer-based in situ direct laser writing

   https://doi.org/10.1039/C9LC00542K  

   Alsharhan, Abdullah T.; Acevedo, Ruben; Warren, Roseanne; Sochol, Ryan D. (August 2019, Lab on a Chip)

   In situ direct laser writing ( is DLW) strategies that facilitate the printing of three-dimensional (3D) nanostructured components directly inside of, and fully sealed to, enclosed microchannels are uniquely suited for manufacturing geometrically complex microfluidic technologies. Recent efforts have demonstrated the benefits of using micromolding and bonding protocols for is DLW; however, the reliance on polydimethylsiloxane (PDMS) leads to limited fluidic sealing ( e.g. , operational pressures <50–75 kPa) and poor compatibility with standard organic solvent-based developers. To bypass these issues, here we explore the use of cyclic olefin polymer (COP) as an enabling microchannel material for is DLW by investigating three fundamental classes of microfluidic systems corresponding to increasing degrees of sophistication: (i) “2.5D” functionally static fluidic barriers (10–100 μm in height), which supported uncompromised structure-to-channel sealing under applied input pressures of up to 500 kPa; (ii) 3D static interwoven microvessel-inspired structures (inner diameters < 10 μm) that exhibited effective isolation of distinct fluorescently labelled microfluidic flow streams; and (iii) 3D dynamically actuated microfluidic transistors, which comprised bellowed sealing elements (wall thickness = 500 nm) that could be actively deformed via an applied gate pressure to fully obstruct source-to-drain fluid flow. In combination, these results suggest that COP-based is DLW offers a promising pathway to wide-ranging fluidic applications that demand significant architectural versatility at submicron scales with invariable sealing integrity, such as for biomimetic organ-on-a-chip systems and integrated microfluidic circuits. 

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4. Laser Fabrication of Polymeric Microneedles for Transdermal Drug Delivery

   Aldawood, Faisal; Desai, Salil; Andar, Abhay (January 2021, Proceedings of the 2021 IISE Annual Conference)

   null (Ed.)

   Microneedles provide a transdermal pathway for drug delivery, cosmetic infusion, vaccine administration, and disease diagnostics. Microneedle fabrication relies on the interplay of several variables which include design parameters, material properties, and processing conditions. In this research, our group explores the effect of design parameters and process variables for laser ablation of microneedles within a Polymethyl methacrylate (PMMA) mold. An Ytterbium laser (200W) was utilized to study the effect of five inputs factors (laser power, pulse width, number of repetitions, laser waveform, and interval time between laser pulses) on two output factors (diameter and height) of the fabricated microneedles. Polydimethylsiloxane (PDMS) polymer was cast within the PMMA microneedle mold. Scanning electron microscopy (SEM) was employed to image topographical features of the microneedles. Further, mechanical testing of the microneedles was conducted to evaluate the buckling load and deformation behavior of the microneedle array. A 20W pulse laser with trapezoidal waveform resulted in optimal microneedle topography with an aspect ratio of 1.2. ANOVA results (α = 0.05) depicted that laser power and number of repetitions were significant factors determining the geometrical features of the microneedle array. This research establishes a framework for the design and manufacturing of customized microneedles for precision medicine. 

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5. High-throughput genetic manipulation of multicellular organisms using a machine-vision guided embryonic microinjection robot

   https://doi.org/10.1093/genetics/iyae025  

   Alegria, Andrew D; Joshi, Amey S; Mendana, Jorge Blanco; Khosla, Kanav; Smith, Kieran T; Auch, Benjamin; Donovan, Margaret; Bischof, John; Gohl, Daryl M; Kodandaramaiah, Suhasa B (February 2024, GENETICS)

   Wildonger, J (Ed.)

   Abstract Microinjection is a technique used for transgenesis, mutagenesis, cell labeling, cryopreservation, and in vitro fertilization in multiple single and multicellular organisms. Microinjection requires specialized skills and involves rate-limiting and labor-intensive preparatory steps. Here, we constructed a machine-vision guided generalized robot that fully automates the process of microinjection in fruit fly (Drosophila melanogaster) and zebrafish (Danio rerio) embryos. The robot uses machine learning models trained to detect embryos in images of agar plates and identify specific anatomical locations within each embryo in 3D space using dual view microscopes. The robot then serially performs a microinjection in each detected embryo. We constructed and used three such robots to automatically microinject tens of thousands of Drosophila and zebrafish embryos. We systematically optimized robotic microinjection for each species and performed routine transgenesis with proficiency comparable to highly skilled human practitioners while achieving up to 4× increases in microinjection throughput in Drosophila. The robot was utilized to microinject pools of over 20,000 uniquely barcoded plasmids into 1,713 embryos in 2 days to rapidly generate more than 400 unique transgenic Drosophila lines. This experiment enabled a novel measurement of the number of independent germline integration events per successfully injected embryo. Finally, we showed that robotic microinjection of cryoprotective agents in zebrafish embryos significantly improves vitrification rates and survival of cryopreserved embryos post-thaw as compared to manual microinjection. We anticipate that the robot can be used to carry out microinjection for genome-wide manipulation and cryopreservation at scale in a wide range of organisms. 

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