Clopidogrel increases risk of pneumonia compared with aspirin in acute ischemic minor stroke patients.

Antiplatelet agents may increase the risk of infections via suppressing platelet-mediated immune response. Here we assessed the contribution of clopidogrel versus aspirin to the development of pneumonia during an acute ischemic stroke admission. A retrospective cohort study was conducted of acute ischemic stroke patients who were admitted to our hospital from 2015 to 2018. Included patients received uninterrupted clopidogrel or aspirin therapy and did not take other antiplatelet agents throughout their stay. The interest outcome was development of pneumonia after stroke. Conditional logistic regression model after propensity score matching and adjusted logistic regression model were used to assess the impact of clopidogrel versus aspirin on post-stroke pneumonia. Among 1470 included patients, 1135 received aspirin and 335 received clopidogrel. Total 149 patients (10.1%) experienced pneumonia during the stroke hospitalization period. No difference was observed between clopidogrel cohort and aspirin cohort in the incidence of post-stroke pneumonia after propensity score matching (relative risk, 1.04; 95% confidence interval (CI) 0.65-1.65; P = 0.875). However, we found that clopidogrel was associated with increased risk of pneumonia compared with aspirin in minor stroke patients (adjusted odds ratio, 2.21; 95% CI 1.12-4.34; P = 0.021), and a statistically insignificant increase of pneumonia in diabetics (adjusted odds ratio, 1.94; 95% CI 0.96-3.94; P = 0.065). Compared with aspirin, clopidogrel is associated with increased pneumonia in minor stroke patients among who the interference of stroke-induced immunosuppression is minimized. Hence, aspirin may be a better choice for minor stroke patients in acute phase of ischemic stroke when pneumonia most frequently occurs.

Axial-Circular Magnetic Levitation: A Three-Dimensional Density Measurement and Manipulation Approach.

Magnetic levitation (MagLev) is a promising technology for density-based analysis and manipulation of diamagnetic objects of various physical forms. However, one major drawback is that MagLev can be performed only along the central axis (one-dimensional MagLev), thereby leading to (i) no knowledge about the magnetic field in regions other than the axial region, (ii) inability to handle objects of similar densities, because they are aggregated in the axial region, and (iii) objects that can be manipulated (e.g., separated or assembled) in only one single direction, that is, the axial direction. This work explores a novel approach called "axial-circular MagLev" to expand the operational space from one dimension to three dimensions, enabling substances to be stably levitated in both the axial and circular regions. Without noticeably sacrificing the total density measurement range, the highest sensitivity of the axial-circular MagLev device can be adjusted up to 1.5 × 104 mm/(g/cm3), approximately 115× better than that of the standard MagLev of two square magnets. Being able to fully utilize the operational space gives this approach greater maneuverability, as the three-dimensional self-assembly of controllable ring-shaped structures is demonstrated. Full space utilization extends the applicability of MagLev to bioengineering, pharmaceuticals, and advanced manufacturing.

Hydrogels: The Next Generation Body Materials for Microfluidic Chips?

The integration of microfluidics with biomedical research is confronted with considerable limitations due to its body materials. With high content of water, hydrogels own superior biocompatibility and degradability. Can hydrogels become another material choice for the construction of microfluidic chips, particularly biofluidics? The present review aims to systematically establish the concept of hydrogel-based microfluidic chips (HMCs) and address three main concerns: i) why choosing hydrogels? ii) how to fabricate HMCs?, and iii) in which fields to apply HMCs? It is envisioned that hydrogels may be used increasingly as substitute for traditional materials and gradually act as the body material for microfluidic chips. The modifications of conventional process are highlighted to overcome issues arising from the incompatibility between the construction methods and hydrogel materials. Specifically targeting at the "soft and wet" hydrogels, an efficient flowchart of "i) high resolution template printing; ii) damage-free demolding; iii) twice-crosslinking bonding" is proposed. Accordingly, a broader microfluidic chip concept is proposed in terms of form and function. Potential biomedical applications of HMCs are discussed. This review also highlights the challenges arising from the material replacement, as well as the future directions of the proposed concept. Finally, the authors' viewpoints and perspectives for this emerging field are discussed.

Electro-Assisted Bioprinting of Low-Concentration GelMA Microdroplets.

Low-concentration gelatin methacryloyl (GelMA) has excellent biocompatibility to cell-laden structures. However, it is still a big challenge to stably fabricate organoids (even microdroplets) using this material due to its extremely low viscosity. Here, a promising electro-assisted bioprinting method is developed, which can print low-concentration pure GelMA microdroplets with low cost, low cell damage, and high efficiency. With the help of electrostatic attraction, uniform GelMA microdroplets measuring about 100 µm are rapidly printed. Due to the application of lower external forces to separate the droplets, cell damage during printing is negligible, which often happens in piezoelectric or thermal inkjet bioprinting. Different printing states and effects of printing parameters (voltages, gas pressure, nozzle size, etc.) on microdroplet diameter are also investigated. The fundamental properties of low-concentration GelMA microspheres are subsequently studied. The results show that the printed microspheres with 5% w/v GelMA can provide a suitable microenvironment for laden bone marrow stem cells. Finally, it is demonstrated that the printed microdroplets can be used in building microspheroidal organoids, in drug controlled release, and in 3D bioprinting as biobricks. This method shows great potential use in cell therapy, drug delivery, and organoid building.

Single-Ring Magnetic Levitation Configuration for Object Manipulation and Density-Based Measurement.

Magnetic levitation is a recent research hot spot; however, most of the extant configurations use two magnets with like poles facing each other. This paper proposes a novel magnetic levitation configuration that is based on a single ring magnet, and this configuration opens a wide operational space that enables object manipulation and density-based measurement. We develop a mathematical model to calculate the magnetic field around the magnet and to numerically correlate the levitation height and density of the object. Experimental results prove that this novel configuration can achieve a high accuracy (±0.0005 to ±0.0078 g/cm3) in density measurement for small-sized (∼5 µL) samples. It can manipulate particles, powders, and oil droplets effectively without any direct contact, and it has high sensitivity in the separation of multiple diamagnetic objects with slight differences in densities as well. The accuracy and sensitivity of the proposed configuration are both higher than those of the extant configurations. All of these results are expected to promote deeper study and applications of the magnetic levitation configuration in the field of density-based characterizations and manipulations.

Fiber-Based Mini Tissue with Morphology-Controllable GelMA Microfibers.

The use of microscale fibers could facilitate nutrient diffusion in fiber-based tissue engineering and improve cell survival. However, in order to build a functional mini tissue such as muscle fibers, nerve conduits, and blood vessels, hydrogel microfibers should not only mimic the structural features of native tissues but also offer a cell-favorable environment and sufficient strength for tissue functionalization. Therefore, an important goal is to fabricate morphology-controllable microfibers with appropriate hydrogel materials to mimic the structural and functional complexity of native tissues. Here, gelatin methacrylate (GelMA) is used as the fiber material due to its excellent biological performance, and a novel coaxial bioprinting method is developed to fabricate morphology-controllable GelMA microfibers encapsulated in calcium alginate. By adjusting the flow rates, GelMA microfibers with straight, wavy, and helical morphologies could be obtained. By varying the coaxial nozzle design, more complex GelMA microfibers such as Janus, multilayered, and double helix structures could be fabricated. Using these microfibers, mini tissues containing human umbilical cord vein endothelial cells are built, in which cells gradually migrate and connect to form lumen resembling blood vessels. The merits of cytocompatibility, structural diversity, and mechanical tunability of the versatile microfibers may open more avenues for further biomedical research.

Airflow-Assisted 3D Bioprinting of Human Heterogeneous Microspheroidal Organoids with Microfluidic Nozzle.

Hydrogel microspheroids are widely used in tissue engineering, such as injection therapy and 3D cell culture, and among which, heterogeneous microspheroids are drawing much attention as a promising tool to carry multiple cell types in separated phases. However, it is still a big challenge to fabricate heterogeneous microspheroids that can reconstruct built-up tissues' microarchitecture with excellent resolution and spatial organization in limited sizes. Here, a novel airflow-assisted 3D bioprinting method is reported, which can print versatile spiral microarchitectures inside the microspheroids, permitting one-step bioprinting of fascinating hydrogel structures, such as the spherical helix, rose, and saddle. A microfluidic nozzle is developed to improve the capability of intricate cell encapsulation with heterotypic contact. Complex structures, such as a rose, Tai chi pattern, and single cell line can be easily printed in spheroids. The theoretical model during printing is established and process parameters are systematically investigated. As a demonstration, a human multicellular organoid of spirally vascularized ossification is reconstructed with this method, which shows that it is a powerful tool to build mini tissues on microspheroids.

Vessel-on-a-chip with Hydrogel-based Microfluidics.

Hydrogel structures equipped with internal microchannels offer more in vivo-relevant models for construction of tissues and organs in vitro. However, currently used microfabrication methods of constructing microfluidic devices are not suitable for the handling of hydrogel. This study presents a novel method of fabricating hydrogel-based microfluidic chips by combining the casting and bonding processes. A twice cross-linking strategy is designed to obtain a bonding interface that has the same strength with the hydrogel bulk, which can be applied to arbitrary combinations of hydrogels. It is convenient to achieve the construction of hydrogel structures with channels in branched, spiral, serpentine, and multilayer forms. The experimental results show that the combination of gelatin and gelatin methacrylate (GelMA) owns the best biocompatibility and can promote cell functionalization. Based on these, a vessel-on-a-chip system with vascular function in both physiological and pathological situations is established, providing a promising model for further investigations such as vascularization, vascular inflammation, tissue engineering, and drug development. Taken together, a facile and cytocompatible approach is developed for engineering a user-defined hydrogel-based chip that can be potentially useful in developing vascularized tissue or organ models.

Self-Sensing of Position-Related Loads in Continuous Carbon Fibers-Embedded 3D-Printed Polymer Structures Using Electrical Resistance Measurement.

Condition monitoring in polymer composites and structures based on continuous carbon fibers show overwhelming advantages over other potentially competitive sensing technologies in long-gauge measurements due to their great electromechanical behavior and excellent reinforcement property. Although carbon fibers have been developed as strain- or stress-sensing agents in composite structures through electrical resistance measurements, the electromechanical behavior under flexural loads in terms of different loading positions still lacks adequate research, which is the most common situation in practical applications. This study establishes the relationship between the fractional change in electrical resistance of carbon fibers and the external loads at different loading positions along the fibers' longitudinal direction. An approach for real-time monitoring of flexural loads at different loading positions was presented simultaneously based on this relationship. The effectiveness and feasibility of the approach were verified by experiments on carbon fiber-embedded three-dimensional (3D) printed thermoplastic polymer beam. The error in using the provided approach to monitor the external loads at different loading positions was less than 1.28%. The study fully taps the potential of continuous carbon fibers as long-gauge sensory agents and reinforcement in the 3D-printed polymer structures.

Study of Pinch-Off Locations during Drop-on-Demand Inkjet Printing of Viscoelastic Alginate Solutions.

The ligament pinch-off process of viscoelastic fluids during jetting is a key step in various biotechnology and dropwise three-dimensional printing applications. Various pinch-off locations have been investigated as a function of material properties and operating conditions during the drop-on-demand (DOD) inkjet printing of viscoelastic alginate solutions. Four breakup types are identified on the basis of the location of the first pinch-off position: front pinching is mainly governed by a balance of inertial and capillary effects, exit pinching is affected by the external actuation-induced hydrodynamic instability and mainly governed by a balance of elastic and capillary effects, middle pinching usually occurs any place along a uniform thin ligament under dominant viscous and elastic effects, and hybrid pinching happens when front pinching and exit pinching occur simultaneously as a special case.

Freeform inkjet printing of cellular structures with bifurcations.

Organ printing offers a great potential for the freeform layer-by-layer fabrication of three-dimensional (3D) living organs using cellular spheroids or bioinks as building blocks. Vascularization is often identified as a main technological barrier for building 3D organs. As such, the fabrication of 3D biological vascular trees is of great importance for the overall feasibility of the envisioned organ printing approach. In this study, vascular-like cellular structures are fabricated using a liquid support-based inkjet printing approach, which utilizes a calcium chloride solution as both a cross-linking agent and support material. This solution enables the freeform printing of spanning and overhang features by providing a buoyant force. A heuristic approach is implemented to compensate for the axially-varying deformation of horizontal tubular structures to achieve a uniform diameter along their axial directions. Vascular-like structures with both horizontal and vertical bifurcations have been successfully printed from sodium alginate only as well as mouse fibroblast-based alginate bioinks. The post-printing fibroblast cell viability of printed cellular tubes was found to be above 90% even after a 24 h incubation, considering the control effect.

Study of droplet formation process during drop-on-demand inkjetting of living cell-laden bioink.

Biofabrication offers a great potential for the fabrication of three-dimensional living tissues and organs by precisely layer-by-layer placing various tissue spheroids as anatomically designed. Inkjet printing of living cell-laden bioink is one of the most promising technologies enabling biofabrication, and the bioink printability must be carefully examined for it to be a viable biofabrication technology. In this study, the cell-laden bioink droplet formation process has been studied in terms of the breakup time, droplet size and velocity, and satellite formation using a time-resolved imaging approach. The bioink has been prepared using fibroblasts and sodium alginate with four different cell concentrations: without cells, 1 × 10(6), 5 × 10(6), and 1 × 10(7) cells/mL to appreciate the effect of cell concentration on the droplet formation process. Furthermore, the bioink droplet formation process is compared with that during the inkjetting of a comparable polystyrene microbead-laden suspension under the identical operating conditions to understand the effect of particle physical properties on the droplet formation process. It is found that (1) as the cell concentration of bioink increases, the droplet size and velocity decrease, the formation of satellite droplets is suppressed, and the breakup time increases, and (2) compared to the hard bead-laden suspension, the bioink tends to have a less ejected fluid volume, lower droplet velocity, and longer breakup time.

Research on a power management system for thermoelectric generators to drive wireless sensors on a spindle unit.

Thermoelectric energy harvesting is emerging as a promising alternative energy source to drive wireless sensors in mechanical systems. Typically, the waste heat from spindle units in machine tools creates potential for thermoelectric generation. However, the problem of low and fluctuant ambient temperature differences in spindle units limits the application of thermoelectric generation to drive a wireless sensor. This study is devoted to presenting a transformer-based power management system and its associated control strategy to make the wireless sensor work stably at different speeds of the spindle. The charging/discharging time of capacitors is optimized through this energy-harvesting strategy. A rotating spindle platform is set up to test the performance of the power management system at different speeds. The experimental results show that a longer sampling cycle time will increase the stability of the wireless sensor. The experiments also prove that utilizing the optimal time can make the power management system work more effectively compared with other systems using the same sample cycle.

Split-Type Magnetic Soft Tactile Sensor with 3D Force Decoupling.

Tactile sensory organs for sensing 3D force, such as human skin and fish lateral lines, are indispensable for organisms. With their sensory properties enhanced by layered structures, typical sensory organs can achieve excellent perception as well as protection under frequent mechanical contact. Here, inspired by these layered structures, a split-type magnetic soft tactile sensor with wireless 3D force sensing and a high accuracy (1.33%) fabricated by developing a centripetal magnetization arrangement and theoretical decoupling model is introduced. The 3D force decoupling capability enables it to achieve a perception close to that of human skin in multiple dimensions without complex calibration. Benefiting from the 3D force decoupling capability and split design with a long effective distance (>20 mm), several sensors are assembled in air and water to achieve delicate robotic operation and water flow-based navigation with an offset <1.03%, illustrating the extensive potential of magnetic tactile sensors in flexible electronics, human-machine interactions, and bionic robots.

Magnetic Soft Catheter Robot System for Minimally Invasive Treatments of Articular Cartilage Defects.

Articular cartilage defects are among the most common orthopedic diseases, which seriously affect patients' health and daily activities, without prompt treatment. The repair biocarrier-based treatment has shown great promise. Total joint injection and open surgery are two main methods to deliver functional repair biocarriers into the knee joint. However, the exhibited drawbacks of these methods hinder their utility. The repair effect of total joint injection is unstable due to the low targeting rate of the repair biocarriers, whereas open surgery causes serious trauma to patients, thereby prolonging the postoperative healing time. In this study, we develop a magnetic soft catheter robot (MSCR) system to perform precise in situ repair of articular cartilage defects with minimal incision. The MSCR processes a size of millimeters, allowing it to enter the joint cavity through a tiny skin incision to reduce postoperative trauma. Meanwhile, a hybrid control strategy combining neural network and visual servo is applied to sequentially complete the coarse and fine positioning of the MSCR on the cartilage defect sites. After reaching the target, the photosensitive hydrogel is injected and anchored into the defect sites through the MSCR, ultimately completing the in situ cartilage repair. The in vitro and ex vivo experiments were conducted on a 3D printed human femur model and an isolated porcine femur, respectively, to demonstrate the potential of our system for the articular cartilage repair.

Biomimetic Hydrodynamic Sensor with Whisker Array Architecture and Multidirectional Perception Ability.

The rapid development of ocean exploration and underwater robot technology has put forward new requirements for underwater sensing methods, which can be used for hydrodynamic characteristics perception, underwater target tracking, and even underwater cluster communication. Here, inspired by the specialized undulated surface structure of the seal whisker and its ability to suppress vortex-induced vibration, a multidirectional hydrodynamic sensor based on biomimetic whisker array structure and magnetic 3D self-decoupling theory is introduced. The magnetic-based sensing method enables wireless connectivity between the magnetic functional structures and electronics, simplifying device design and endowing complete watertightness. The 3D self-decoupling capability enables the sensor, like a seal or other organisms, to perceive arbitrary whisker motions caused by the action of water flow without complex calibration and additional sensing units. The whisker sensor is capable of detecting a variety of hydrodynamic information, including the velocity (RMSE < 0.061 m s-1) and direction of the steady flow field, the frequency (error < 0.05 Hz) of the dynamic vortex wake, and the orientation (error < 7°) of the vortex wake source, demonstrating its extensive potential for underwater environmental perception and communication, especially in deep sea conditions.

Functional Blood-Brain Barrier Model with Tight Connected Minitissue by Liquid Substrates Culture.

The functional blood-brain barrier (BBB) model can provide a reliable tool for better understanding BBB transport mechanisms and in vitro preclinical experimentation. However, recapitulating microenvironmental complexities and physiological functions in an accessible approach remains a major challenge. Here, a new BBB model with a high-cell spatial density and tightly connected biomimetic minitissue is presented. The minitissue, pivotal functional structure of the BBB model, is fabricated by a novel and easy-to-use liquid substrate culture (LSC) method, which allows cells to self-assemble and self-heal into macrosized, tightly connected membranous minitissue. The minitissue with uniform thickness can be easily harvested in their entirety with extracellular matrix. Attributed to the tightly connected minitissue formed by LSC, the fabricated BBB biomimetic model has 1 to 2 orders of magnitude higher transendothelial electric resistance than the commonly reported BBB model. It also better prevents the transmission of large molecular substances, recapitulating the functional features of BBB. Furthermore, the BBB biomimetic model provides feedback regarding BBB-destructive drugs, exhibits selective transmission, and shows efflux pump activity. Overall, this model can serve as an accessible tool for life science or clinical medical researchers to enhance the understanding of human BBB and expedite the development of new brain-permeable drugs.

Liquid Metal Microgels for Three-Dimensional Printing of Smart Electronic Clothes.

Gallium-based liquid metals (LMs), with the combination of liquid fluidity and metallic conductivity, are considered ideal conductive components for flexible electronics. However, huge surface tension and poor wettability seriously hinder the patterning of LMs and their wider applications. Herein, a recyclable liquid-metal-microgel (LMM) ink composed of LM droplets encapsulated into alginate microgel shells is proposed. During the mechanical stirring process, the released Ga3+ can cross-link with sodium alginate to form microgels covering the surface of LM droplets, which exhibits shear-thinning performance due to the formation and rupture of hydrogen bonds under different stress conditions, making the LMM ink possess excellent printability and superior adhesion to various substrates. Although patterns printed with the LMM ink are not initially conductive, they can be activated to recover conductivity by microstrain (<5%), pressing, and freezing. Additionally, the activated LMM circuit exhibits superior Joule heating behaviors and electrical performance in further investigation, including excellent conductivity, significant resistance response to strain with small hysteresis, great durability to nonplanar forces, and so forth. Furthermore, smart electronic clothes were fabricated and investigated by directly printing functional circuits on commercial clothes with the LMM ink, which integrate multiple functions, including tactile sensing, motion monitoring, human-computer interaction, and thermal management.

Balancing the customization and standardization: exploration and layout surrounding the regulation of the growing field of 3D-printed medical devices in China.

Medical devices are instruments and other tools that act on the human body to aid clinical diagnosis and disease treatment, playing an indispensable role in modern medicine. Nowadays, the increasing demand for personalized medical devices poses a significant challenge to traditional manufacturing methods. The emerging manufacturing technology of three-dimensional (3D) printing as an alternative has shown exciting applications in the medical field and is an ideal method for manufacturing such personalized medical devices with complex structures. However, the application of this new technology has also brought new risks to medical devices, making 3D-printed devices face severe challenges due to insufficient regulation and the lack of standards to provide guidance to the industry. This review aims to summarize the current regulatory landscape and existing research on the standardization of 3D-printed medical devices in China, and provide ideas to address these challenges. We focus on the aspects concerned by the regulatory authorities in 3D-printed medical devices, highlighting the quality system of such devices, and discuss the guidelines that manufacturers should follow, as well as the current limitations and the feasible path of regulation and standardization work based on this perspective. The key points of the whole process quality control, performance evaluation methods and the concept of whole life cycle management of 3D-printed medical devices are emphasized. Furthermore, the significance of regulation and standardization is pointed out. Finally, aspects worthy of attention and future perspectives in this field are discussed.

Ultrasonic autofocus imaging of internal voids in multilayer polymer composite structures.

Multilayer polymer composite structures have been playing important roles in various fields, but the voids inside are not allowed in most scenarios. Ultrasonic technology has been widely used to inspect voids in concrete and metal structures. However, the application of ultrasonic imaging in polymer composite structures is severely blocked by the coating and lamination structures and unstable manufacturing induced sound speed variations. In this paper, a method to autofocus imaging of internal voids in multilayer polymer composite structures with ultrasonic phased array is firstly proposed. The method processes the full matrix capture (FMC) and focuses all voids in the multilayer structure automatically without the prior information of the speed of sound (SOS). The method utilizes the focus criterions to evaluate the focusing quality and then estimates the SOS with differential evolution layer by layer from surface to deep, which improves the robustness and computational efficiency. The method was examined with simulation data from three multilayer structures and well-focused all voids with position error less than 0.6 mm and SOS error less than 6 %. Moreover, the method was verified with the experimental data and focused voids with position error less than 1 mm.