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Extraordinary properties of traditional hyperbolic metamaterials, not found in nature, arise from their man-made subwavelength structures causing unique light-matter interactions. However, their preparation requiring nanofabrication processes is highly challenging and merely provides nanoscale two-dimensional structures. Stabilizing their bulk forms via scalable procedures has been a sought-goal for broad applications of this technology. Herein, we report a new strategy of designing and realizing bulk metamaterials with finely tunable hyperbolic responses. We develop a facile two-step process: (1) self-assembly to obtain heterostructured nanohybrids of building blocks and (2) consolidation to convert nanohybrid powders to dense bulk pellets. Our samples have centimeter-scale dimensions typically, readily further scalable. Importantly, the thickness of building blocks and their relative concentration in bulk materials serve as a delicate means of controlling hyperbolic responses. The resulting new bulk heterostructured material system consists of the alternating h-BN and graphite/graphene nanolayers and exhibits significant modulation in both type-I and type-II hyperbolic resonance modes. It is the first example of real bulk hyperbolic metamaterials, consequently displaying the capability of tuning their responses along both in-plane and out-of-plane directions of the materials for the first time. It also distinctly interacts with unpolarized and polarized transverse magnetic and electronic beams to give unique hyperbolic responses. Our achievement can be a new platform to create various bulk metamaterials without complicated nanofabrication techniques. Our facile synthesis method using common laboratory techniques can open doors to broad-range researchers for active interdisciplinary studies for this otherwise hardly accessible technology.

Nature materials (2021). doi:10.1038/s41563-021-01064-6, Published by Nature Publishing Group, Basingstoke

Liver fibrosis is a critical liver disease which can lead to liver cirrhosis, cancer, and liver failure. Among various etiological factors, activated stellate cells are a major factor that can induce liver fibrosis. Several studies have presented in vitro models to identify drugs for liver fibrosis; however, there are still limitations in terms of the 2D culture conditions, random co-culture of liver cells, and lack of extracellular matrix components. Therefore, a 3D liver fibrosis-on-a-chip was developed with three liver cell types (hepatocytes, activated stellate cells, and endothelial cells) using a novel cell-printing technique with gelatin bioinks, which were used to deliver each nonparenchymal liver cell type as a multilayer construct. Liver fibrosis-specific gene expression, collagen accumulation, cell apoptosis, and reduced liver functions caused by activated stellate cells were also evaluated. Furthermore, previously reported chemicals were added to the 3D liver fibrosis-on-a-chip to examine the downregulation of activated hepatic stellate cells. In conclusion, the developed 3D liver fibrosis-on-a-chip could be used as a potential in vitro model in the research field.

Retinal pigment epithelium (RPE) is a monolayer of the pigmented cells that lies on the thin extracellular matrix called Bruch&rsquo, s membrane. This monolayer is the main component of the outer blood&ndash, retinal barrier (BRB), which plays a multifunctional role. Due to their crucial roles, the damage of this epithelium causes a wide range of diseases related to retinal degeneration including age-related macular degeneration, retinitis pigmentosa, and Stargardt disease. Unfortunately, there is presently no cure for these diseases. Clinically implantable RPE for humans is under development, and there is no practical examination platform for drug development. Here, we developed porcine Bruch&rsquo, s membrane-derived bioink (BM-ECM). Compared to conventional laminin, the RPE cells on BM-ECM showed enhanced functionality of RPE. Furthermore, we developed the Bruch&rsquo, s membrane-mimetic substrate (BMS) via the integration of BM-ECM and 3D printing technology, which revealed structure and extracellular matrix components similar to those of natural Bruch&rsquo, s membrane. The developed BMS facilitated the appropriate functions of RPE, including barrier and clearance functions, the secretion of anti-angiogenic growth factors, and enzyme formation for phototransduction. Moreover, it could be used as a basement frame for RPE transplantation. We established BMS using 3D printing technology to grow RPE cells with functions that could be used for an in vitro model and RPE transplantation.

Bi2Te3-based materials are a representative thermoelectric system operating near ambient temperature. Their n-type family is very limited and underperforms the p-type counterpart, which is a major concern in the thermoelectric community. Here we report that alkali earth metals (AE = Mg, Ca, Sr, Ba) in Group 2 unusually induce n-type thermoelectric properties in Bi2Te3. Mg is the most efficient electron donor among them. The x = 0.01 sample of MgxBi2-xTe3 (x = 0.005, 0.01, 0.015) system exhibits remarkably enhanced power factor and ZT of ~0.8 at 350 K in comparison with pristine Bi2Te3. The improved performance is attributed to simultaneously enhanced electrical conductivity and reduced lattice thermal conductivity. Remarkably, MgxBi2-xTe3 materials show larger Seebeck coefficients than those expected by the theoretical Pisarenko relation.

3D cell-printing technique has been under spotlight as an appealing biofabrication platform due to its ability to precisely pattern living cells in pre-defined spatial locations . In skin tissue engineering , a major remaining challenge is to seek for a suitable source of bioink capable of supporting and stimulating printed cells for tissue development. However, current bioinks for skin printing rely on homogeneous biomaterials , which has several shortcomings such as insufficient mechanical properties and recapitulation of microenvironment . In this study, we investigated the capability of skin-derived extracellular matrix (S-dECM) bioink for 3D cell printing-based skin tissue engineering. S-dECM was for the first time formulated as a printable material and retained the major ECM compositions of skin as well as favorable growth factors and cytokines. This bioink was used to print a full thickness 3D human skin model. The matured 3D cell-printed skin tissue using S-dECM bioink was stabilized with minimal shrinkage, whereas the collagen-based skin tissue was significantly contracted during in vitro tissue culture. This physical stabilization and the tissue-specific microenvironment from our bioink improved epidermal organization, dermal ECM secretion, and barrier function. We further used this bioink to print 3D pre-vascularized skin patch able to promote in vivo wound healing. In vivo results revealed that endothelial progenitor cells (EPCs)-laden 3D-printed skin patch together with adipose-derived stem cells (ASCs) accelerates wound closure, re-epithelization, and neovascularization as well as blood flow. We envision that the results of this paper can provide an insightful step towards the next generation source for bioink manufacturing.

The generation of physiologically aligned multinucleated myotubes is critical in the fabrication of functional engineered skeletal muscle. Although micro-/nano-topographical contact guidance, such as groove/ridge structures, has induced the alignment of muscle fibers by providing cells with extracellular matrix (ECM) topography, the complex biochemical microenvironment of the ECM cannot be recapitulated. Here, we report the enhancement of myogenic differentiation and maturation using muscle decellularized ECM (mdECM) and sinusoidal wavy surfaces, which provided a biochemical microenvironment and microscale contact guidance, respectively. Sinusoidal wavy polystyrene surfaces with wavelengths of 20, 40, and 80 μm were fabricated by a deep X-ray lithography-based process. The mdECM was prepared by decellularization of porcine tibialis anterior skeletal muscle. An mdECM coating significantly improved the surface wettability of polystyrene substrates and exhibited higher seeding efficiency, cell viability, and proliferation compared with collagen- and non-coating cases. The sinusoidal wavy surfaces induced well-aligned myotubes and showed significantly enhanced formation of myotubes and myogenic differentiation when the surface was coated with mdECM. Particularly, there was an approximately 1.5-2 fold improvement in morphological analysis and gene expression for mdECM-compared to non-coated sinusoidal wavy surfaces. These results suggest that the consideration of both topographical and biochemical environmental cues can generate a highly mimicked ECM environment, thereby providing cells with a synergistic effect on myogenic differentiation and maturation. The outcome of this study will be useful in developing of functional engineered muscle for application in tissue regeneration or a high-throughput in vitro model for drug screening.

Polybenzimidazole containing graphitic carbon nitride moiety (PBICN) is prepared by in situ polymerization of 3,3′-diaminobenzidine (DAB), isophthalic acid (IPA), and graphitic carbon nitride (g-CN) for the application in high-temperature fuel cell membrane. Since g-CN has a nanosheet structure and lots of amine end groups, it can be involved in the polymerization process producing PBI-grafted g-CN. The PBICN membrane shows much improved thermal property, oxidative stability, mechanical strength, and proton conductivity compared to pristine PBI membrane and the PBI composite membrane prepared simply by mixing PBI and g-CN. In addition, it is confirmed that the PBI-grafted g-CN structure formed during the in situ polymerization can contribute to the increase of the dimensional stability for the PBICN membrane. Especially, PBICN membrane prepared by the in situ polymerization using g-CN exhibits much improved fuel cell performance. For example, the power density value of the membrane electrode assembly (MEA) fabricated using PBICN membrane prepared using 0.5 wt% of g-CN is 400 mW cm−2, which is much larger than those of MEA fabricated using PBI membrane (241 mW cm−2) and the PBI composite membrane containing 0.5 wt% of g-CN (326 mW cm−2) membrane during the fuel cell performance test performed at 160 °C without humidification.

The liver is an important organ and plays major roles in the human body. Because of the lack of liver donors after liver failure and drug-induced liver injury, much research has focused on developing liver alternatives and liver in vitro models for transplantation and drug screening. Although numerous studies have been conducted, these systems cannot faithfully mimic the complexity of the liver. Recently, three-dimensional (3D) cell printing technology has emerged as one of a number of innovative technologies that may help to overcome this limitation. However, a great deal of work in developing biomaterials optimized for 3D cell printing-based liver tissue engineering remains. Therefore, in this work, we developed a liver decellularized extracellular matrix (dECM) bioink for 3D cell printing applications and evaluated its characteristics. The liver dECM bioink retained the major ECM components of the liver while cellular components were effectively removed and further exhibited suitable and adjustable properties for 3D cell printing. We further studied printing parameters with the liver dECM bioink to verify the versatility and fidelity of the printing process. Stem cell differentiation and HepG2 cell functions in the liver dECM bioink in comparison to those of commercial collagen bioink were also evaluated, and the liver dECM bioink was found to induce stem cell differentiation and enhance HepG2 cell function. Consequently, the results demonstrate that the proposed liver dECM bioink is a promising bioink candidate for 3D cell printing-based liver tissue engineering.

3D cell printing technology is in the spotlight for producing 3D tissue or organ constructs useful for various medical applications. In printing of neuromuscular tissue, a bioink satisfying all the requirements is a challenging issue. Gel integrity and motor neuron activity are two major characters because a harmonious combination of extracellular materials essential to motor neuron activity consists of disadvantages in mechanical properties. Here, a method for fabrication of 3D neuromuscular tissue is presented using a porcine central nervous system tissue decellularized extracellular matrix (CNSdECM) bioink. CNSdECM retains CNS tissue-specific extracellular molecules, provides rheological properties crucial for extrusion-based 3D cell printing, and reveals positive effects on the growth and maturity of axons of motor neurons compared with Matrigel. It also allows long-term cultivation of human-induced-pluripotent-stem-cell-derived lower motor neurons and sufficiently supports their cellular behavior to carry motor signals to muscle fibers. CNSdECM bioink holds great promise for producing a tissue-engineered motor system using 3D cell printing.

To overcome the drawbacks of in vitro liver testing during drug development, numerous liver-on-a-chip models have been developed. However, current liver-on-a-chip technologies are labor-intensive, lack extracellular matrix (ECM) essential for liver cells, and lack a biliary system essential for excreting bile acids, which contribute to intestinal digestion but are known to be toxic to hepatocytes. Therefore, fabrication methods for development of liver-on-a-chip models that overcome the above limitations are required. Cell-printing technology enables construction of complex 3D structures with multiple cell types and biomaterials. We used cell-printing to develop a 3D liver-on-a-chip with multiple cell types for co-culture of liver cells, liver decellularized ECM bioink for a 3D microenvironment, and vascular/biliary fluidic channels for creating vascular and biliary systems. A chip with a biliary fluidic channel induced better biliary system creation and liver-specific gene expression and functions compared to a chip without a biliary system. Further, the 3D liver-on-a-chip showed better functionalities than 2D or 3D cultures. The chip was evaluated using acetaminophen and it showed an effective drug response. In summary, our results demonstrate that the 3D liver-on-a-chip we developed is promising in vitro liver test platform for drug discovery.

© 2015 American Chemical Society. Near-infrared (NIR) dye-sensitized upconversion nanoparticles (UCNPs) can broaden the absorption range and boost upconversion efficiency of UCNPs. Here, we achieved significantly enhanced upconversion luminescence in dye-sensitized core/active shell UCNPs via the doping of ytterbium ions (Yb3+) in the UCNP shell, which bridged the energy transfer from the dye to the UCNP core. As a result, we synergized the two most practical upconversion booster effectors (dye-sensitizing and core/shell enhancement) to amplify upconversion efficiency. We demonstrated two biomedical applications using these UCNPs. By using dye-sensitized core/active shell UCNP embedded poly(methyl methacrylate) polymer implantable systems, we successfully shifted the optogenetic neuron excitation window to a biocompatible and deep tissue penetrable 800 nm wavelength. Furthermore, UCNPs were water-solubilized with Pluronic F127 with high upconversion efficiency and can be imaged in a mouse model.

The synthetic elastomer based on acrylonitrile butadiene rubber (NBR) has been recently developed as a kind of dielectric elastomer actuators (DEAs). Its advantages are that its properties can be modified according to the requirements of applications. In this paper, we report a comprehensive study on the effects of plasticizers including diisodecyl phthalate (DIDP), dioctyladipate (DOA), and dioctyl phthalate (DOP) as well as a high dielectric additive, which is, barium titanate (BaTiO3) with respect to the overall performance of the synthetic elastomer. We investigate how the significant parameters representing the actuator performance can be changed according to the composition of the additives and how the actuation performances can be improved. In addition, we address how the environmental conditions such as exposure to the light and the air have influence on the properties of the synthetic elastomer, and a method for extending the lifetime of DEA is also addressed. Open image in new window

Recently, numerous three-dimensional (3D) bioprinting systems have been introduced for the artificial regeneration of tissues. Among them, the extrusion-based dispensing module is the most widely used because of the processability it gives various biomaterials. The module uses high forces and temperature to dispense materials through a micro-nozzle. Generally, the harsh conditions induce thermal degradation of the material in the dispensing procedure. The thermal degradation affects the properties of the materials, and the change of the properties should be carefully controlled, because it severely affects the regeneration of tissues. Therefore, in this research, the relationship between the dispensing module and the thermal degradation of material was investigated. Extrusion-based dispensing modules can be divided into the syringe type (ST) and filament type (FT) based on working principles. We prepared a poly lactic-co-glycolic acid (PLGA) scaffold with the two methods at various time points. Then, the characteristics of the printed scaffolds were assessed by measuring molecular weight (M w), glass transition temperature (T g), in vitro degradation, compressive modulus, and cytocompatibility. The results showed that the PLGA scaffold with the FT dispensing module maintained its properties regardless of printing time points. In contrast, severe thermal degradation was observed in the scaffold group prepared by the ST dispensing module. Consequentially, it was obvious that the FT dispensing module was more suitable for producing scaffolds without severe thermal degradation.

Due to its simplicity and effectiveness, the physical blending of polymers is considered to be a practical strategy for developing a versatile scaffold having desirable mechanical and biochemical properties. In the present work, an indirect three-dimensional (i3D) printing technique was proposed to fabricate a 3D free-form scaffold using a blend of immiscible materials, such as polycaprolactone (PCL) and gelatin. The i3D printing technique includes 3D printing of a mold and a sacrificial molding process. PCL/chloroform and gelatin/water were physically mixed to prepare the blend solution, which was subsequently injected into the cavity of a 3D printed mold. After solvent removal and gelatin cross-linking, the mold was dissolved to obtain a PCL-gelatin (PG) scaffold, with a specific 3D structure. Scanning electron microscopy and Fourier transform infrared spectroscopy analysis indicated that PCL masses and gelatin fibers in the PG scaffold homogenously coexisted without chemical bonding. Compression tests confirmed that gelatin incorporation into the PCL enhanced its mechanical flexibility and softness, to the point of being suitable for soft-tissue engineering, as opposed to pure PCL. Human adipose-derived stem cells, cultured on a PG scaffold, exhibited enhanced in vitro chondrogenic differentiation and tissue formation, compared with those on a PCL scaffold. The i3D printing technique can be used to blend a variety of materials, facilitating 3D scaffold fabrication for specific tissue regeneration. Furthermore, this convenient and versatile technique may lead to wider application of 3D printing in tissue engineering.

(n-Hexadecylsulfonyl)methyl-substituted poly(oxyethylene) (16SP), (n-hexadecylthio)methyl-substituted poly(oxyethylene) (16TP), [(6-n-nonylsulfonyl)hexylthio]methyl-substituted poly(oxyethylene) (9S6TP), and [(6-n-nonylsulfonyl)hexylsulfonyl]methyl-substituted poly(oxyethylene) (9S6SP) were synthesized. 9S6SP and 16SP containing sulfonylmethyl side groups showed highly ordered smectic layer structures at room temperature and liquid crystalline behavior at higher temperatures, while 9S6TP and 16TP containing thiomethyl side groups did not show any liquid crystalline behavior. The ordered phases of the polymers were studied using differential scanning calorimetry, cross-polarizing optical microscopy, and X-ray diffraction. The unusual liquid crystallinity of 16SP and 9S6SP was ascribed to the amphiphilic character of these polymers.

In order to establish a noninvasive cancer therapy with minimal side effects, low cost, and specific in targeting tumor cells. The team engineered novel and biocompatible Upconversion Nanoparticles (UCNPs) with a calcium fluoride shell α-NaYF4:Yb, Er@CaF2 and conjugated with an FDA approved prodrug 5-Aminolevulinic Acid (ALA). In conjunction with photodynamic therapy (PDT), deep tissue penetration was achieved. UCNPs convert near-infrared light into visible light when excited at ~980nm. Emission of the red light from the UCNPs activate the photosensitizer protoporphyrin (PpIX), causing the production of reactive oxygen species (ROS) causing the death of targeted tumor.