Search Results (35)

Microneedle (MN) technologies have emerged as a groundbreaking platform for transdermal and intradermal drug delivery, offering a minimally invasive alternative to oral and parenteral routes. Unlike passive transdermal systems, MNs allow the permeation of hydrophilic macromolecules, such as peptides, proteins, and vaccines, by penetrating the stratum corneum barrier without causing pain or tissue damage, unlike hypodermic needles. Recent advances in materials science, microfabrication, and biomedical engineering have enabled the development of various MN types, including solid, coated, dissolving, hollow, hydrogel-forming, and hybrid designs. Each type has unique mechanisms, fabrication techniques, and pharmacokinetic profiles, providing customized solutions for a range of therapeutic applications. The integration of 3D printing technologies and stimulus-responsive polymers into MN systems has enabled patches that combine drug delivery with real-time physiological sensing. Over the years, MN applications have grown beyond vaccines to include the delivery of insulin, anticancer agents, contraceptives, and various cosmeceutical ingredients, highlighting the versatility of this platform. Despite this progress, broader clinical and commercial adoption is still limited by issues such as scalable and reliable manufacturing, patient acceptance, and meeting regulatory expectations. Overcoming these barriers will require coordinated efforts across engineering, clinical research, and regulatory science. This review thoroughly summarizes MN technologies, beginning with their classification and drug-delivery mechanisms, and then explores innovations, therapeutic uses, and translational challenges. It concludes with a critical analysis of clinical case studies and a future outlook for global healthcare. By comparing technological progress with regulatory and commercial hurdles, this article highlights the opportunities and limitations of MN systems as a next-generation drug-delivery platform. Full article

Hollow microneedle (HMN) systems can deliver insulin with minimal pain, but most rely on external pumps that add bulk, cost, and failure modes. This paper reports the design, fabrication, and mechanical characterisation of a pump-free, refillable HMN patch that integrates a syringe-loadable, self-sealing reservoir and delivers by passive diffusion. A 3 × 4 array of side-orifice conical HMNs with a target height of 1 mm and a bore of 0.8 mm was stereolithography-printed in dental-grade resin and coupled to an elastic-grade resin septum that maintains a leak-free seal after repeated needle puncture. A surface-response design of experiments (DoE) probed wall thickness of 0.10–0.20 mm, post-cure time of 20–60 min, and temperatures of 35–80 °C. The microneedle characteristics include geometric fidelity, insertion into multilayer Parafilm, and axial compression to 150 N. All patches were printed with a hollow channel and side orifices with tips were slightly blunted. Relative to the original design, height undershoot was from −24.5% to −60.5% while base diameters were within −11% to +20%. Parafilm insertion exhibited a peak then force drop at about 0.22 mm displacement with 1.2–1.5 N pierced the first layer. It was found that about 90% of needles penetrated about 381 µm and more than 20% reached 635 µm. Patches withstood 150 N without fracture with strains of 9.7–15.6% and modulus of 8–48 MPa. ANOVA identified wall thickness as a significant factor, with curing temperature not being significant. Contour analysis defined an operating window near a 0.15 mm wall and about 40 min post-cure balancing dimensional fidelity and post-compression height retention. These results define a manufacturable path to compact, pump-free insulin patches with low insertion force and robust mechanics, opening a clinically scalable route to simpler everyday insulin therapy. Full article

Traditional emitters used for downhole acoustic detection have limited radiation frequency and energy, making it difficult to transmit high-precision acoustic signals over long distances. This paper presents a plasma emitter in which high-pressure discharge generates a powerful spherical impulse wave with a wide frequency range. First, the discharge characteristics of the plasma needle-plate emitter are analyzed using high-voltage discharge experiments and discharge simulation models for underwater emitters. Subsequently, advanced modifications are made to the structure of the needle–plate emitter to meet the requirements of downhole detection. A new type of hollow needle–plate emitter with a spherical tip is developed. The results show that the structural optimization of the hollow needle–plate emitter with a spherical tip resulted in a 27.2% increase in impulse wave amplitude, a 28.1% improvement in electro-acoustic conversion efficiency, and a radiation frequency band covering up to 100 kHz. This development is conducive to more accurate and longer-range downhole structure detection. The detection range outside the borehole can reach tens to hundreds of meters. This enables the precise control of the wellbore path and reduces the demands on the rig’s build rate. The emitter has significant application potential in areas such as onshore and offshore oil and gas exploration, unconventional resource detection, impulse wave fracturing and wellbore clearance, and rescue and U-well drilling. Full article

Additive manufacturing (AM) has become a key element of Industry 4.0, particularly the extrusion AM (EAM) of thermoplastic materials, which is recognized as the most widely used technology. Fused Filament Fabrication (FFF), however, depends on expensive commercially available filaments, making pellet extruder-based EAM techniques more desirable. Large-format EAM systems could benefit from printing lightweight objects with reduced material use and lower power consumption by utilizing hollow rather than solid extrudates. In this study, a custom extruder head was designed and an EAM system capable of extruding inflatable hollow extrudates from a variety of materials was developed. By integrating a co-axial nozzle-needle system, a thermoplastic shell was extruded while creating a hollow core using pressurized nitrogen gas. This method allows for the production of objects with gradient part density and varied mechanical properties by controlling the inflation of the hollow extrudates. The effects of process parameters— such as extrusion temperature, extrusion speed, and gas pressure were investigated—using poly-lactic acid (PLA) and styrene-ethylene-butylene-styrene (SEBS) pellets. The preliminary tests identified the optimal range of these parameters for consistent hollow extrudates. We then varied the parameters to determine their impact on the dimensions of the extrudates, supported by analyses of microscopic images taken with an optical microscope. Our findings reveal that pressure is the most influential factor affecting extrudate dimensions. In contrast, variations in temperature and extrusion speed had a relatively minor impact, whereas changes in pressure led to significant alterations in the extrudate’s size and shape. Full article

Background/Objectives: Microneedle(MN)-based drug delivery is one of the potential approaches to overcome the limitations of oral and hypodermic needle delivery. An in silico model has been developed for hollow microneedle (HMN)-based drug delivery in the skin and its subsequent absorption in the blood and tissue compartments in the presence of interstitial flow. The drug’s reversible specific saturable binding to its receptors and the kinetics of reversible absorption across the blood and tissue compartments have been taken into account. Methods: The governing equations representing the flow of interstitial fluid, the transport of verapamil in the viable skin and the concentrations in the blood and tissue compartments are solved using combined Marker and Cell and Immersed Boundary Methods to gain a quantitative understanding of the model under consideration. Results: The viscoelastic skin is predicted to impede the transport of verapamil in the viable skin and, hence, reduce the concentrations of all forms in the blood and the tissue compartments. The findings reveal that a higher mean concentration in the viable skin is not always associated with a longer MN length. Simulations also predict that the concentrations of verapamil in the blood and bound verapamil in the tissue compartment rise with decreasing tip diameters. In contrast, the concentration of free verapamil in the tissue increases with increasing injection velocities. Conclusions: The novelty of this study includes verapamil metabolism in two-dimensional viscoelastic irregular viable skin and the nonlinear, specific, saturable, and reversible binding of verapamil in the tissue compartment. The tip diameter and the drug’s injection velocity are thought to serve as regulatory parameters for the effectiveness and efficacy of MN-mediated therapy if the MN is robust enough to sustain the force needed to penetrate a wider tip into the skin. Full article

Additive manufacturing (AM) has emerged as one of the core components of the fourth industrial revolution, Industry 4.0. Among others, the extrusion AM (EAM) of thermoplastic materials has been named as the most widely adopted technology. Fused filament fabrication (FFF) relies on the commercial availability of expensive filaments; hence, pellet extruder-based EAM techniques are desired. Large-format EAM systems would benefit from the ability to print lightweight objects with less materials and lower power consumption, which is possible with the use of hollow extrudates rather than solid extrudates to print objects. In this work, we designed a custom extruder head and developed an EAM system that allows the extrusion of inflatable hollow extrudates of a relatively wide material choice. By incorporating a co-axial nozzle–needle system, a thermoplastic shell was extruded while the hollow core was generated by using pressurized nitrogen gas. The ability to print using hollow extrudates with controllable inflation allows us to print objects with gradient part density with different degrees of mechanical properties. In this article, the effect of different process parameters, namely, extrusion temperature, extrusion speed, and gas pressure, were studied using poly-lactic acid (PLA) pellets. Initially, a set of preliminary tests was conducted to identify the maximum and minimum ranges of these parameters that result in consistent hollow extrudates. Finally, the parameters were varied to understand how they affect the core diameter and shell thickness of the hollow extrudates. These findings were supported by analyses of microscopic images taken under an optical microscope. Full article

Temperature can reflect vital activities, and researchers have attempted to guide Chinese medicine diagnosis and treatment by observing acupoint temperature changes. Integrating a temperature sensor at the needle tip enables in situ acupoint temperature measurement. However, the sensor needles for acupoint temperature monitoring designed in previous studies were fabricated by manually soldering thermistor beads and metal wires, making mass production difficult. In this work, using MEMS manufacturing technology, a flexible temperature sensor that can be integrated at the needle tip is proposed and can be mass-produced on silicon wafers. The sensor uses a Pt thermistor as the temperature-sensing element and has a slender flexible structure with dimensions of 125 μm width by 3.2 cm length. As the sensor is inserted into a hollow needle, the Pt thermistor is glued to the needle tip. In the temperature range of 30 °C to 50 °C, the fabricated temperature sensor has a sensitivity of 5.00 Ω∙°C⁻¹, a nonlinearity of ±0.39%FS, and a repeatability error of ±2.62%FS. Additionally, the sensor has been applied to in vivo acupoint temperature monitoring experiments in rats and demonstrated good performance, suggesting its promise for future research on acupoint temperature. Full article

A large number of non-degradable materials have severely damaged the ecological environment. Now, people are increasingly pursuing the use of environmentally friendly materials to replace traditional chemical materials. Polyhydroxyalkonates (PHAs) are receiving increasing attention because of the unique biodegradability and biocompatibility they offer. However, the applications of PHAs are still limited due to high production costs and insufficient study. This project examines the optimal electrospinning parameters for the production of PHA-based fibrous membranes for air filtration. A common biodegradable polyester, Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), was electrospun into a nanofibrous membrane with a well-controlled surface microstructure. In order to produce smooth, bead-free fibers with micron-scale diameters, the effect of the process parameters (applied electric field, solution flow rate, inner diameter of hollow needle, and polymer concentration) on the electrospun fiber microstructure was optimized. The well-defined fibrous structure was optimized at an applied electric field of 20 kV, flow rate of 0.5 mL/h, solution concentration of 12 wt.%, and needle inner diameter of 0.21 mm. The morphology of the electrospun PHBV fibrous membrane was observed by scanning electron microscopy (SEM). Fourier transform infrared (FTIR) and Raman spectroscopy were used to explore the chemical signatures and phases of the electrospun PHBV nanofiber. The ball burst strength (BBS) was measured to assess the mechanical strength of the membrane. The small pore size of the nanofiber membranes ensured they had good application prospects in the field of air filtration. The particle filtration efficiency (PFE) of the optimized electrospun PHBV fibrous membrane was above 98% at standard atmospheric pressure. Full article

In the past years the number of hospital autopsies have declined steadily, becoming almost excluded from medical training. Medicolegal (forensic) autopsies account for almost all autopsies, whereas hospital autopsies are becoming increasingly rare. Minimally invasive tissue sampling (MITS) using post mortem ultrasound offers the opportunity to increase the number of post mortem examinations in a clinical and even forensic context. MITS is a needle-based post mortem procedure that uses (radiological) imaging techniques to examine major organs of the body, acquire tissue samples and aspirate fluid from the body cavities or hollow organs. In this study, MITS was used to determine the presence of other co-existing diseases in a deceased infected 97-year-old woman with severe acute respiratory syndrome coronavirus 2. The examination of her body was carried out using ultrasound as an imaging tool and to gather ultrasound-guided biopsies as conventional autopsy was rejected by the next of kin. Ultrasound and histology identified an intravesical mass leading to an obstruction of the urinary outlet resulting in bilateral hydronephrosis and purulent pyelonephritis, which was unknown during her lifetime. Histopathological examination revealed the tumor mass to be a squamous cell carcinoma. This study has shown that MITS can be used to determine the cause of death and the presence of concomitant diseases in the infectious deceased. Full article

The Development of bioresponsive extrudable hydrogels for 3D bioprinting is imperative to address the growing demand for scaffold design as well as efficient and reliable methods of tissue engineering and regenerative medicine. This study proposed genipin (5 mg) cross-linked gelatin (1 to 1.5 g)-hyaluronic acid (0.3 g) hydrogel bioink (20 mL) tailored for 3D bioprinting. The focus is on high cell loading and a less artificial extra-cellular matrix (ECM) effect, as well as exploring their potential applications in tissue engineering. The bioresponsiveness of these hydrogel scaffolds was successfully evaluated at 37 °C and room temperature (at pH 2.5, 7.4, and 9). The rheological and mechanical properties (more than three times) increased with the increase in gelatin content in the hydrogel; however, the hydrogel with the least amount of gelatin showed the best extrusion capability. This optimized hydrogel’s high extrusion ability and post-printing shape fidelity were evident from 3D and four-axis printing of complex structures such as hollow tubes, stars, pyramids, and zigzag porous tubular (four-axis) scaffolds (printed at 90 kPa pressure, 70 mm/s speed, 22G needle, fourth axis rotation of 4 rpm). 3 million/mL MC3T3-E1 mouse osteoblast cells were used in preparing 3D bioprinted samples. The in vitro cell culture studies have been carried out in a CO₂ incubator (at 37 °C, 5% CO₂). In the cytocompatibility study, almost three times more cell viability was observed in 3 days compared to day 1 control, proving the non-toxicity and cell-supportiveness of these hydrogels. High cell viability and cell-to-cell interactions observed at the end of day 3 using this moderately stable hydrogel in 3D bioprinting exhibit high potential for precise cell delivery modes in tissue engineering as well as regenerative medicine. Full article

Of the digital concrete-additive-manufacturing techniques, extrusion-based systems are probably the most widespread and studied. Despite the significant potential offered by 3D printing, several challenges must still be overcome. For instance, although several solutions have already been explored, the automated reinforcement of the layer-wise printed structures represents a challenge. The inline quality control of the fresh-state properties of 3D-printed materials is also an open question that needs to be addressed to find an efficient shared practice. This study proposes a new device designed to simultaneously reinforce 3D-printed structures along and through the layers and to be used as an inline quality-control device. This device consists in a sewing system, which is composed of a rotating system, and a hollow needle, which drives a reinforcing cable or yarn and can be used to inject cement grout to fill holes and improve bonding with reinforcement. The rotation is induced by a stepper motor, which measures the torque that is required to make the needle penetrate. This measurement can be used as a quality-control index to ensure material homogeneity. This paper aims to present an original reinforcement system that can be fully automated and simultaneously create reinforcement patterns in different directions of the printed structure while controlling the material’s fresh properties. Full article

Microneedles (MNs) are considered to be a novel smart injection system that causes significantly low skin invasion upon puncturing, due to the micron-sized dimensions that pierce into the skin painlessly. This allows transdermal delivery of numerous therapeutic molecules, such as insulin and vaccines. The fabrication of MNs is carried out through conventional old methods such as molding, as well as through newer and more sophisticated technologies, such as three-dimensional (3D) printing, which is considered to be a superior, more accurate, and more time- and production-efficient method than conventional methods. Three-dimensional printing is becoming an innovative method that is used in education through building intricate models, as well as being employed in the synthesis of fabrics, medical devices, medical implants, and orthoses/prostheses. Moreover, it has revolutionary applications in the pharmaceutical, cosmeceutical, and medical fields. Having the capacity to design patient-tailored devices according to their dimensions, along with specified dosage forms, has allowed 3D printing to stand out in the medical field. The different techniques of 3D printing allow for the production of many types of needles with different materials, such as hollow MNs and solid MNs. This review covers the benefits and drawbacks of 3D printing, methods used in 3D printing, types of 3D-printed MNs, characterization of 3D-printed MNs, general applications of 3D printing, and transdermal delivery using 3D-printed MNs. Full article

Interventional biopsy needles need to be accurately localized to the target tissue during magnetic resonance imaging (MRI) interventions. In this context, severe susceptibility artifacts affect the visibility of structures in the MR images depending on the needle’s material composition. In particular, standard needles for the spinal cord made of nickel-titanium alloys (NiTi) generate massive susceptibility artifacts during MRI. Consequently, this does not allow the precise placement of the needle to the target. The aim was to prove that using a non-metallic material for the needle can significantly reduce the appearance of artifacts. Hence, this work used a new combination of non-metallic materials based on an enforced fiber bundle as an inner core with different outer hollow sheets to fabricate seven prototypes of interventional spinal needles to optimize their visualization in MRI scans. Susceptibility artifacts for the non-metallic needles were evaluated in MRI images by an automatic quantification based on a K-means algorithm and compared with manual quantification. The width and length of the artifacts were measured for each needle. The non-metallic needles showed significantly lower artifacts in comparison to the standard needle. K-means provided the capability for detecting needle artifacts in MRI images, facilitating qualitative and quantitative assessment of MRI artifacts. Full article

Liquid crystal (LC) grating has drawn extensive attention due to its merits, including tunability, easy preparation process, cost effectiveness, and high diffraction efficiency. However, limited efforts have been made to explore LC grating for the generation of customized diffraction patterns, despite the fact that the patterning size of LC molecular director orientation has been tremendously reduced even to subwavelength scale via high-precision photoalignment techniques. Here, we propose a versatile method based on the binary particle swarm optimization algorithm to efficiently design aperiodic LC gratings for customized optical patterns generation, including needle beam, multi-foci, and hollow beam. The optical performance of the LC gratings was simulated using both the vectorial Rayleigh–Sommerfeld method (with discrete zero or π phase, in this article) and the actual director orientations. These results matched each other well, which proves the effectiveness of the optimization method based on discrete phase. This study paves the way for designing LC gratings with engineered functionalities, which may find applications in optical tweezers, laser delivery systems, and laser scanning imaging. Full article

Fabrication of micro- and nanofibers are critical for a wide range of applications from microelectronics to biotechnology. Alginate microfibers with diameters of tens to hundreds of microns play an important role in tissue engineering and fibers of these diameters are impossible to fabricate via electrospinning and can only be produced via fluidic spinning. Typically, microfluidic spinning based on photopolymerization produces fibers that are not easily dissolvable, while fluidic spinning with chemical cross-linking employs complex setups of microfabricated chips or coaxial needles, aimed at precise control of the fiber diameter; however, fluidic spinning introduces significant cost and complexity to the microfluidic setup. We demonstrate immersed microfluidic spinning where a calcium alginate microfiber is produced via displacement of alginate solution through a single needle that is immersed in a cross-linking bath of calcium chloride solution. The resulting diameter of the fiber is characterized and the fiber diameter and topology of the deposited fiber is related to the concentration of the alginate solution (2 wt%, 4 wt%, and 6 wt%), needle gauge (30 g, 25 g, and 20 g), and the volumetric flow rate of the alginate solution (1 mL/min, 2 mL/min, and 2.7 mL/min). The resulting fiber diameter is smaller than the internal diameter of the needle and this dependence is explained by the continuity of the flow and increased rate of fall of the liquid jet upon its issuing from the needle. The fiber diameter (demonstrated diameter of fibers range from 100 microns to 1 mm) depends weakly on the volumetric flow rate and depends strongly on the needle diameter. It also seems that for a smaller needle size, a greater concentration of alginate results in smaller diameter fibers and that this trend is not evident as the needle diameter is increased. In terms of topology of the deposited fiber, the higher wt% alginate fiber produces larger loops, while smaller wt% alginate solution yields a denser topology of the overlaid fiber loops. These fibers can be dissolved in DMEM/EDTA/DSC solution in 20–30 min (depending on the fiber diameter), leaving behind the hollow channels in the hydrogel matrix. We believe that the demonstrated simple setup of the immersed microfluidic spinning of the calcium alginate microfibers will be useful for creating tissue constructs, including the vascularized tissue implants. Full article