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.

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.

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.

Perfusable Vessel-on-a-Chip for Antiangiogenic Drug Screening with Coaxial Bioprinting.

Vessel-on-a-chips, which can be used to study microscale fluid dynamics, tissue-level biological molecules delivery and intercellular communication under favorable three-dimensional (3D) extracellular matrix microenvironment, are increasingly gaining traction. However, not many of them can allow for long-term perfusion and easy observation of angiogenesis process. Since angiogenesis is necessary for the expansion of tumor, antiangiogenic drugs play a significant role in cancer treatment. In this study, we established an innovative and reliable antiangiogenic drug screening chip that was highly modularly integrated for long-term perfusion (up to 10 days depending on the hydrogel formula) and real-time monitoring. To maintain an unobstructed flow of cell-laden tubes for subsequent perfusion culture on the premise of excellent bioactivities, a polycaprolactone stent inspired by coronary artery stents was introduced to hold up the tubular lumen from the inside, while the perfusion chip was also elaborately designed to allow for convenient observation. After 3 days of perfusion screening, distinct differences in human umbilical vein endothelial cell sprouting were observed for a gradient of concentrations of bevacizumab, which pointed to the effectiveness and reliability of the drug screening perfusion system. Overall, a perfusion system for antiangiogenic drug screening was developed, which can not only conduct drug evaluation, but also be potentially useful in other vessel-mimicking scenarios in the area of tissue engineering, drug screening, pharmacokinetics, and regenerative medicine.

Thermo-sensitive Sacrificial Microsphere-based Bioink for Centimeter-scale Tissue with Angiogenesis.

Centimeter-scale tissue with angiogenesis has become more and more significant in organ regeneration and drug screening. However, traditional bioink has obvious limitations such as balance of nutrient supporting, printability, and vascularization. Here, with "secondary bioprinting" of printed microspheres, an innovative bioink system was proposed, in which the thermo-crosslinked sacrificial gelatin microspheres encapsulating human umbilical vein endothelial cells (HUVECs) printed by electrospraying serve as auxiliary component while gelatin methacryloyl precursor solution mixed with subject cells serve as subject component. Benefiting from the reversible thermo-crosslinking feature, gelatin microspheres would experience solid-liquid conversion during 37°C culturing and form controllable porous nutrient network for promoting the nutrient/oxygen delivery in large-scale tissue and accelerate the functionalization of the encapsulated cells. Meanwhile, the encapsulated HUVECs would be released and attach to the pore boundary, which would further form three-dimensional vessel network inside the tissue with suitable inducing conditions. As an example, vascularized breast tumor tissue over 1 cm was successfully built and the HUVECs showed obvious sprout inside, which indicate the great potential of this bioink system in various biomedical applications.

Wireless Flexible Magnetic Tactile Sensor with Super-Resolution in Large-Areas.

Tactile recognition is among the basic survival skills of human beings, and advances in tactile sensor technology have been adopted in various fields, bringing benefits such as outstanding performance in manipulating objects and general human-robot interactions. However, promoting enhanced perception of the existing tactile sensors is limited by their sensor array arrangement and wire-connected design. Here we present a wireless flexible magnetic tactile sensor (FMTS) consisting of a multidirection magnetized flexible film (perception module) and a contactless Hall sensor (signal receiving module). The flexible magnetic film is composed of NdFeB microparticles and soft silicone elastomer microparticles, and it transfers the unambiguous transduction of external force position and magnitude into magnetic signals. Benefiting from the specific magnetization arrangement and clustering algorithm, only one Hall sensor is needed in FMTS to perceive the magnitude and position of the contact spot simultaneously with super-resolution (2.1 mm average error) on a large area (3600 mm2), and the effective working distance is also greatly extended (∼30 mm), allowing for the full softness and adaptability to diverse conditions. We anticipate that this design will promote the development of soft tactile sensors and their integration into human-robot interaction and humanoid robot perception.

In situ 3D bioprinting with bioconcrete bioink.

In-situ bioprinting is attractive for directly depositing the therapy bioink at the defective organs to repair them, especially for occupations such as soldiers, athletes, and drivers who can be injured in emergency. However, traditional bioink displays obvious limitations in its complex operation environments. Here, we design a bioconcrete bioink with electrosprayed cell-laden microgels as the aggregate and gelatin methacryloyl (GelMA) precursor solution as the cement. Promising printability is guaranteed with a wide temperature range benefiting from robust rheological properties of photocrosslinked microgel aggregate and fluidity of GelMA cement. Composite components simultaneously self-adapt to biocompatibility and different tissue mechanical microenvironment. Strong binding on tissue-hydrogel interface is achieved by hydrogen bonds and friction when the cement is photocrosslinked. This bioink owns good portability and can be easily prepared in urgent accidents. Meanwhile, microgels can be cultured to mini tissues and then mixed as bioink aggregates, indicating our bioconcrete can be functionalized faster than normal bioinks. The cranial defects repair results verify the superiority of this bioink and its potential in clinical settings required in in-situ treatment.

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.

Printability during projection-based 3D bioprinting.

Since projection-based 3D bioprinting (PBP) could provide high resolution, it is well suited for printing delicate structures for tissue regeneration. However, the low crosslinking density and low photo-crosslinking rate of photocurable bioink make it difficult to print fine structures. Currently, an in-depth understanding of the is lacking. Here, a research framework is established for the analysis of printability during PBP. The gelatin methacryloyl (GelMA)-based bioink is used as an example, and the printability is systematically investigated. We analyze the photo-crosslinking reactions during the PBP process and summarize the specific requirements of bioinks for PBP. Two standard quantized models are established to evaluate 2D and 3D printing errors. Finally, the better strategies for bioprinting five typical structures, including solid organs, vascular structures, nerve conduits, thin-wall scaffolds, and micro needles, are presented.

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.

Recyclable conductive nanoclay for direct in situ printing flexible electronics.

Liquid-metal (LM)-based flexible and stretchable electronics have attracted widespread interest in wearable health monitoring, electronic skins, and soft robotics. However, it is challenging to directly pattern LMs on soft substrates to form desirable functional circuits due to their huge surface tension and weak wettability. Here, a recyclable, self-healing conductive nanoclay is prepared by introducing nanoclay into the LM system, which possesses low fluidity and excellent adhesion to soft substrates, and combined with the stamping process, flexible electronics can be printed directly and quickly in situ. Conductive nanoclay possesses great conductivity, significant electrical response to deformation, very low electric hysteresis and excellent damage mitigation ability, making it an ideal direct-printable ink for rapid manufacturing of flexible electronics. Owing to unique structure composition, conductive nanoclay can grow in a vacuum and maintain excellent conductivity, based on which vacuum-on switches that can be used in extreme environments such as outer space are fabricated without complex structural design. Furthermore, the electronic tattoos possessing excellent conformity with the skin were directly printed in situ on the wrist and can be employed to monitor the motion of the wrist along two different bending directions.

Electrospinning of Nanofibrous Membrane and Its Applications in Air Filtration: A Review.

Air pollution caused by particulate matter and toxic gases is violating individual's health and safety. Nanofibrous membrane, being a reliable filter medium for particulate matter, has been extensively studied and applied in the field of air purification. Among the different fabrication approaches of nanofibrous membrane, electrospinning is considered as the most favorable and effective due to its advantages of controllable process, high production efficiency, and low cost. The electrospun membranes, made of different materials and unique structures, exhibit good PM2.5 filtration performance and multi-functions, and are used as masks and filters against PM2.5. This review presents a brief overview of electrospinning techniques, different structures of electrospun nanofibrous membranes, unique characteristics and functions of the fabricated membranes, and summarization of the outdoor and indoor applications in PM filtration.

3D Printing of Physical Organ Models: Recent Developments and Challenges.

Physical organ models are the objects that replicate the patient-specific anatomy and have played important roles in modern medical diagnosis and disease treatment. 3D printing, as a powerful multi-function manufacturing technology, breaks the limitations of traditional methods and provides a great potential for manufacturing organ models. However, the clinical application of organ model is still in small scale, facing the challenges including high cost, poor mimicking performance and insufficient accuracy. In this review, the mainstream 3D printing technologies are introduced, and the existing manufacturing methods are divided into "directly printing" and "indirectly printing", with an emphasis on choosing suitable techniques and materials. This review also summarizes the ideas to address these challenges and focuses on three points: 1) what are the characteristics and requirements of organ models in different application scenarios, 2) how to choose the suitable 3D printing methods and materials according to different application categories, and 3) how to reduce the cost of organ models and make the process simple and convenient. Moreover, the state-of-the-art in organ models are summarized and the contribution of 3D printed organ models to various surgical procedures is highlighted. Finally, current limitations, evaluation criteria and future perspectives for this emerging area are discussed.

Research on the Fused Deposition Modeling of Polyether Ether Ketone.

As a special engineering polymer, polyether ether ketone (PEEK) has been used widely due to its excellent mechanical properties, high thermal stability, and chemical resistance. Fused deposition modeling (FDM) is a promising process for fabricating PEEK parts. However, due to the semi-crystalline property and high melting point of PEEK, determining appropriate process parameters is important to reduce warpage deformation and improve the mechanical properties of PEEK. In this article, the influence of raster angle and infill density was determined by single factor experiment, which are the two most important parameters. The results showed that samples with 0°/90° raster angle and 50% infill density had the best comprehensive properties in terms of warpage deformation, tensile strength, and specific strength. Subsequently, based on the results above, the effects of printing speed, nozzle temperature, platform temperature, raster width, and layer thickness were analyzed by orthogonal experiment. The results indicated that platform temperature had the greatest impact on warpage deformation while printing speed and nozzle temperature were significant parameters on tensile strength. Through optimization, warpage deformation of the samples could be reduced to almost 0 and tensile strength could increase by 19.6% (from 40.56 to 48.50 MPa). This will support the development of FDM for PEEK.

High-Performance Auxetic Bilayer Conductive Mesh-Based Multi-Material Integrated Stretchable Strain Sensors.

High-performance stretchable strain sensors, particularly those with high sensitivity and broad sensing range, are highly important for wearable devices. Herein, a novel auxetic bilayer conductive mesh strain sensor (ABSS), composed of multi-hardness silicones, is proposed and fabricated by the direct ink writing 3D printing and ink spraying technique. The bilayer conductive mesh comprises a thin layer of high-conductive and crack-prone single-walled carbon nanotubes (SWCNTs) coated on a stretchable carbon-black-doped Ecoflex silicone rubber (CB/Ecoflex) mesh. The former serves as the dominant sensing material by generating SWCNT cracks in the full strain range, while the latter mainly plays the roles of both generating the resistance change and maintaining the conductive paths under high strain conditions. The presence of high-hardness auxetic frame contributes to the formation of longitudinal SWCNT cracks on transverse meshes, enhancing the sensitivity of the sensors. It is shown that the synergistic effect of the bilayer conductive mesh, strain concentration, and auxetic deformation strategy endow ABSS with a high gauge factor (∼ 13.4) that is 6.6 times larger than that of the common sensor. Additionally, this study demonstrates the superior sensing performance of the ABSS for wearable applications including swallowing recognition, respiration monitoring, and joint movement detection.

Automatic magnetic projection for one-step separation of mixed plastics using ring magnets.

Magnetic projection, a novel separation method proposed recently, can separate multiple mixed materials in an efficient and low-cost way. Although promising, existing magnetic projection method cannot achieve the automatic feeding of mixed materials, which limits its applications. To address this challenge, ring magnets were used to replace conventional square magnets in this research. Specifically, a mixture of particles with different densities were fed through the hole of ring magnets and then projected to the corresponding area. Moreover, to increase the magnetic field strength, magnets were superimposed. To predict the projection process, magnetic field analysis was conducted. And from the results, an interesting trap area was found, where the separated materials may be constrained, leading to the failure of projection. The simulation of the projection process revealed that with the increase of the number of magnets (1-3 magnets), the magnetic field strength increased. However, the projection distance will not keep increasing with the increase of the magnetic field strength, which also was verified by experiments (Err within 10%). Based on this principle, an automatic feeding device with ring track and pendulum was designed and manufactured. In the separation experiment, six different plastics, that were PP, ABS, PC, PLA, PET and PVC, were used to verify the separation effect. The experimental results showed that the proposed method can automatically separate a plastic mixture with a recovery rate of over 95%. This study presents a break-through in magnetic projection, laying the foundation for the practical application of magnetic projection.

Fabrication of a dual-layer cell-laden tubular scaffold for nerve regeneration and bile duct reconstruction.

Tubular scaffolds serve as a controllable extracellular environment to guide the repair and regeneration of tissues. But it is still a challenge to achieve both excellent mechanical properties and cell compatibility of artificial scaffolds for long-term structural and biological stability. In this study, a four-step solution casting method was developed to fabricate dual-layer cell-laden tubular scaffolds for nerve and bile duct regeneration. The dual-layer tubular scaffold consisted of a bone marrow mesenchymal stem cells (BMSCs)-laden hydrogel inner layer and an outer layer of gelatin methacrylate (GelMA)/polyethylene glycol diacrylate. While the inner layer had a good biocompatibility, the outer layer had desired mechanical properties. The interfacial toughness, Young's modulus, maximum tensile strain, and compressive modulus of dual-layer tubular scaffolds were 65 J m-2, 122.37 ± 23.21 kPa, 100.87 ± 40.10%, and 39.14 ± 18.56 N m-1, respectively. More importantly, the fabrication procedure was very cell-friendly, since the BMSC viability encapsulated in the inner layer of 10% (w/v) GelMA reached 94.68 ± 0.43% after 5 d of culture. Then, a preliminary evaluation of the potential application of dual-layer tubular scaffolds as nerve conduits and biliary scaffolds was performed, and demonstrated that the cell-laden dual-layer tubular scaffolds proposed in this work are expected to extend the application of tubular scaffolds in tissue engineering.

A flexible porous chiral auxetic tracheal stent with ciliated epithelium.

Tracheal stent placement is a principal treatment for tracheobronchial stenosis, but complications such as mucus plugging, secondary stenosis, migration, and strong foreign body sensation remain unavoidable challenges. In this study, we designed a flexible porous chiral tracheal stent intended to reduce or overcome these complications. The stent was innovatively designed with a flexible tetrachiral and anti-tetrachiral hybrid structure as the frame and hollows filled with porous silicone sponge. Detailed finite element analysis (FEA) showed that the designed frame can maintain a Poisson's ratio that is negative or close to zero at up to 50% tensile strain. This contributes to improved airway ventilation and better resistance to migration during physiological activities such as respiration and neck movement. The preparation process combined indirect 3D printing with gas foaming and particulate leaching methods to efficiently fabricate the stent. The stent was then subjected to uniaxial tension and local radial compression tests, which indicated that it not only has the same desirable auxetic performance but also has flexibility similar to the native trachea. The porous sponge facilitated the adhesion of cells, allowed nutrient diffusion, and would prevent the ingrowth of granulation tissue. Furthermore, a ciliated tracheal epithelium similar to that of the native trachea was differentiated from normal human bronchial primary epithelial cells on the internal wall of the stent under air-liquid interface conditions. These results suggest that the designed stent has the potential for application in the treatment of tracheobronchial stenosis.

A Mechanically Robust and Versatile Liquid-Free Ionic Conductive Elastomer.

Soft ionic conductors, such as hydrogels and ionogels, have enabled stretchable and transparent ionotronics, but they suffer from key limitations inherent to the liquid components, which may leak and evaporate. Here, novel liquid-free ionic conductive elastomers (ICE) that are copolymer networks hosting lithium cations and associated anions via lithium bonds and hydrogen bonds are demonstrated, such that they are intrinsically immune from leakage and evaporation. The ICEs show extraordinary mechanical versatility including excellent stretchability, high strength and toughness, self-healing, quick self-recovery, and 3D-printability. More intriguingly, the ICEs can defeat the conflict of strength versus toughness-a compromise well recognized in mechanics and material science-and simultaneously overcome the conflict between ionic conductivity and mechanical properties, which is common for ionogels. Several liquid-free ionotronics based on the ICE are further developed, including resistive force sensors, multifunctional ionic skins, and triboelectric nanogenerators (TENGs), which are not subject to limitations of previous gel-based devices, such as leakage, evaporation, and weak hydrogel-elastomer interfaces. Also, the 3D printability of the ICEs is demonstrated by printing a series of structures with fine features. The findings offer promise for a variety of ionotronics requiring environmental stability and durability.