Injectable Hydrogel Guides Neurons Growth with Specific Directionality.

Visual disabilities affect more than 250 million people, with 43 million suffering from irreversible blindness. The eyes are an extension of the central nervous system which cannot regenerate. Neural tissue engineering is a potential method to cure the disease. Injectability is a desirable property for tissue engineering scaffolds which can eliminate some surgical procedures and reduce possible complications and health risks. We report the development of the anisotropic structured hydrogel scaffold created by a co-injection of cellulose nanofiber (CNF) solution and co-polypeptide solution. The positively charged poly (L-lysine)-r-poly(L-glutamic acid) with 20 mol% of glutamic acid (PLLGA) is crosslinked with negatively charged CNF while promoting cellular activity from the acid nerve stimulate. We found that CNF easily aligns under shear forces from injection and is able to form hydrogel with an ordered structure. Hydrogel is mechanically strong and able to support, guide, and stimulate neurite growth. The anisotropy of our hydrogel was quantitatively determined in situ by 2D optical microscopy and 3D X-ray tomography. The effects of PLLGA:CNF blend ratios on cell viability, neurite growth, and neuronal signaling are systematically investigated in this study. We determined the optimal blend composition for stimulating directional neurite growth yielded a 16% increase in length compared with control, reaching anisotropy of 30.30% at 10°/57.58% at 30°. Using measurements of calcium signaling in vitro, we found a 2.45-fold increase vs. control. Based on our results, we conclude this novel material and unique injection method has a high potential for application in neural tissue engineering.

The feedback loop between miR-21, PDCD4 and AP-1 functions as a driving force for renal fibrogenesis.

Renal fibrosis is a final common pathway of chronic kidney disease. Sustained activation of fibroblasts is considered to play a key role in perpetuating renal fibrosis but the driving force in the perpetuation stage is only partially understood. To date, some investigations have specifically identified overexpression of microRNA 21 (miR-21) in the progression of kidney fibrosis. Nevertheless, the precise role of miR-21 in fibroblast activation remains largely unknown. In this study, we found that miR-21 was significantly upregulated in activated fibroblasts and that it maintained itself at constant high levels by employing an auto-regulatory loop between miR-21, PDCD4 and AP-1. Persistently upregulated miR-21 suppressed protein expression of Smad7 and, eventually, enhanced the TGF-ß1/Smad pathway to promote fibroblast activation. More importantly, we found miR-21 sequestration with miR-21 antagomir or AP-1 inhibitors attenuated unilateral ureteral obstruction (UUO)-induced renal fibrosis. miR-21-knockout mice also suffered far less interstitial fibrosis in response to kidney injury. Altogether, these data suggest that miR-21 is a main driving force of fibroblast activation and keeps its high expression level by employing a double negative autoregulatory loop. Targeting this aberrantly activated feedback loop may provide new therapeutic strategy in treating fibrotic kidneys.

Achieving High-Performance Perovskite Photovoltaic by Morphology Engineering of Low-Temperature Processed Zn-Doped TiO2 Electron Transport Layer.

Perovskite solar cells (PSCs) have become one of the most promising renewable energy converting devices. However, in order to reach a sufficiently high power conversion efficiency (PCE), the PSCs typically require a high-temperature sintering process to prepare mesostructured TiO2 as an efficient electron transport layer (ETL), which prohibits the PSCs from commercialization in the future. This work investigates a low-temperature synthesis of TiO2 nanocrystals and introduces a two-fluid spray coating process to produce a nanostructured ETL for the following deposition of perovskite layer. The temperature during the whole deposition process can be maintained under 150 °C. Compared to the typical planar TiO2 layer, the perovskite layer fabricated on a nanostructured TiO2 layer shows uniform compactness, preferred orientation, and high crystallinity, leading to reproducible and promising device performance. The detail mechanisms are revealed by the contact angle test, morphology characterization, grazing incident wide angle X-Ray scattering measurement, and space charge limited currents analysis. Finally, optimized device performance can be achieved through adequate Zn doping in the TiO2 layer, demonstrating an average PCE of 19.87% with champion PCE of 21.36%. The efficiency can maintain over 80% of its original value after 3000 h storage in ambient atmosphere. This study suggests a promising approach to offer high-efficiency PSCs using the low-temperature process.

Oligo(ethylene glycol) side chain effect on the physical properties and molecular arrangement of oligothiophene-isoindigo based conjugated polymers.

Oligo(ethylene glycol) (OEG) side chains are widely used in donor-acceptor conjugated polymers (D-A CPs) and enable the polymers to dissolve and be processed in environmentally friendly and cost-effective nonchlorinated solvents, such as water. However, the OEG effect on the physical properties of D-A CPs has not been thoroughly studied and sometimes the results are controversial. In this study, two oligothiophene-isoindigo based conjugated polymers, P3TI and P4TI, are selected as model polymers to investigate the OEG effect. PnTI has octyl side chains on the oligothiophene unit and 2-hexyldecyl side chains on the isoindigo unit. The replacement of an alkyl side chain with OEG not only changes the optical and thermal properties but also the molecular arrangements of the polymers such as π-π d-spacing, crystallinity, and packing orientation. The domination of the crystallization behavior changes from the oligothiophene unit to the isoindigo unit when the bulky alkyl group is replaced by the flexible and linear OEG. The packing changes from edge-on to face-on orientation. The results are intriguing and provide new insights into this class of polymers.

Polybenzyl Glutamate Biocompatible Scaffold Promotes the Efficiency of Retinal Differentiation toward Retinal Ganglion Cell Lineage from Human-Induced Pluripotent Stem Cells.

Optic neuropathy is one of the leading causes of irreversible blindness caused by retinal ganglion cell (RGC) degeneration. The development of induced pluripotent stem cell (iPSC)-based therapy opens a therapeutic window for RGC degeneration, and tissue engineering may further promote the efficiency of differentiation process of iPSCs. The present study was designed to evaluate the effects of a novel biomimetic polybenzyl glutamate (PBG) scaffold on culturing iPSC-derived RGC progenitors. The iPSC-derived neural spheres cultured on PBG scaffold increased the differentiated retinal neurons and promoted the neurite outgrowth in the RGC progenitor layer. Additionally, iPSCs cultured on PBG scaffold formed the organoid-like structures compared to that of iPSCs cultured on cover glass within the same culture period. With RNA-seq, we found that cells of the PBG group were differentiated toward retinal lineage and may be related to the glutamate signaling pathway. Further ontological analysis and the gene network analysis showed that the differentially expressed genes between cells of the PBG group and the control group were mainly associated with neuronal differentiation, neuronal maturation, and more specifically, retinal differentiation and maturation. The novel electrospinning PBG scaffold is beneficial for culturing iPSC-derived RGC progenitors as well as retinal organoids. Cells cultured on PBG scaffold differentiate effectively and shorten the process of RGC differentiation compared to that of cells cultured on coverslip. The new culture system may be helpful in future disease modeling, pharmacological screening, autologous transplantation, as well as narrowing the gap to clinical application.

Highly Conductive 2D Metal-Organic Framework Thin Film Fabricated by Liquid-Liquid Interfacial Reaction Using One-Pot-Synthesized Benzenehexathiol.

Metal-organic frameworks (MOF) are studied extensively in applications like catalysts, gas storage, and sensors due to their various functional groups and structures. Two-dimensional (2D) MOFs such as triphenylene-based materials show excellent charge transport properties, but thin-film fabrication and organic ligand synthesis are difficult. In this work, we synthesize thiol-based organic ligand, benzenehexathiol (BHT), by a simple one-pot reaction. This facile method is safer and faster than conventional synthesis procedure that requires using liquid ammonia as solvent. Two novel 2D MOF materials, Ag3BHT2 and Au3BHT2, are fabricated by coordinating BHT with either silver (Ag) or gold (Au) ions through liquid-liquid interfacial reaction. The Ag3BHT2 thin film reaches a high electrical conductivity of 363 S cm-1, which has potential applications in electronic devices and sensors.

Quantitative correlation of the effects of crystallinity and additives on nanomorphology and solar cell performance of isoindigo-based copolymers.

The high power conversion efficiency of bulk heterojunction (BHJ) polymer solar cells can be achieved from either low crystallinity (P3TI) or high crystallinity (P6TI) of isoindigo-based donor-acceptor alternating copolymers blended with PC71BM by controlling nanophase separation using additives. P3TI shows similar device performance regardless of the type of additives, while P6TI is significantly affected by whether the additive is aliphatic or aromatic. To understand the interplays of crystallinity of polymers and the type of additive on the formation of nanomorphology of BHJ, we employed the simultaneous grazing-incidence small- and wide-angle X-ray scattering (GISAXS and GIWAXS) technique to perform the quantitative investigation. By incorporating additives, the PC71BM molecules can be easily intercalated into the P3TI polymer-rich domain and the size of the PC71BM clusters is reduced from about 24 nm to about 5 nm by either aliphatic 1,8-diiodooctane (DIO) or aromatic 1-chloronaphthalene (CN). On comparison, it is found to be more difficult for PC71BM molecules to be intercalated into the highly crystalline P6TI dense domain, and the PC71BM molecules have a higher tendency to be self-aggregated, which results in a larger size of PC71BM clusters of about 58 nm. The clusters can be reduced to about 7 nm by DIO and 13 nm by CN. The presence of crystallites in the P6TI domain can interact with the additive to tailor the crystallization of PC71BM clusters to a size similar to that of P6TI crystallites (∼12 nm) and form a connected network for efficient charge transportation. Thus, the power conversion efficiency of P6TI:PC71BM reaches its maximum of 7.04% using aromatic CN additives. This is a new finding of the effect of crystallinity, which is not observed in the common low crystalline donor-acceptor alternating copolymers such as PTB7. Our results provide a useful guideline to manipulate the desired morphology of BHJ films constructed from alternating copolymer with different crystallinity, which is critical for achieving high power conversion efficiency of solar cells.

Secreted fibroblast-derived miR-34a induces tubular cell apoptosis in fibrotic kidney.

Tubular epithelial cell apoptosis contributes to tubulointerstitial fibrosis but its regulation remains unclear. Here, in fibrotic kidney induced by unilateral ureteral obstruction (UUO), we demonstrate that miR-34a is markedly upregulated in tubulointerstitial spaces and microvesicles isolated from obstructed kidney. However, miR-34a is not de novo synthesized by proximal tubular epithelial cells but by fibroblasts after incubation with TGF-ß1. miR-34a is markedly upregulated in microvesicles isolated from the cell culture medium of TGF-ß1-treated fibroblasts. These microvesicles act as a vector for delivery of upregulated miR-34a from fibroblasts to tubular cells. The fibroblast-derived miR-34a-containing microvesicles induce the apoptosis of tubular cells. The exogenous miR-34a regulates tubular apoptosis by modulating the expression of the anti-apoptotic protein Bcl-2. Moreover, injection of exogenous miR-34a-containing microvesicles enhances tubular cell apoptosis in mice. This study suggests that secreted fibroblast miR-34a transported by microvesicles induces tubular cell apoptosis in obstructed kidney. This study reveals a new mechanism whereby microvesicle-mediated communication of miRNA between fibroblasts and tubular cells is involved in regulating tubular cell apoptosis, which might provide new therapeutic targets for renal tubulointerstitial fibrosis.

Romantic Story or Raman Scattering? Rose Petals as Ecofriendly, Low-Cost Substrates for Ultrasensitive Surface-Enhanced Raman Scattering.

In this Article, we present a facile approach for the preparation of ecofriendly substrates, based on common rose petals, for ultrasensitive surface-enhanced Raman scattering (SERS). The hydrophobic concentrating effect of the rose petals allows us to concentrate metal nanoparticle (NP) aggregates and analytes onto their surfaces. From a systematic investigation of the SERS performance when using upper and lower epidermises as substrates, we find that the lower epidermis, with its quasi-three-dimensional (quasi-3D) nanofold structure, is the superior biotemplate for SERS applications. The metal NPs and analytes are both closely packed in the quasi-3D structure of the lower epidermis, thereby enhancing the Raman signals dramatically within the depth of focus (DOF) of the Raman optical system. We have also found the effect of the pigment of the petals on the SERS performance. With the novel petal-based substrate, the SERS measurements reveal a detection limit for rhodamine 6G below the femtomolar regime (10(-15) M), with high reproducibility. Moreover, when we employ an upside-down drying process, the unique effect of the Wenzal state of the hydrophobic petal surface further concentrate the analytes and enhanced the SERS signals. Rose petals are green, natural materials that appear to have great potential for use in biosensors and biophotonics.

Kinetically Enhanced Approach for Rapid and Tunable Self-Assembly of Rod-Coil Block Copolymers.

A facile approach is reported to process rod-coil block copolymers (BCPs) into highly ordered nanostructures in a rapid, low-energy process. By introducing a selective plasticizer into the rod-coil BCPs during annealing, both the annealing temperature and time to achieve thermodynamic equilibrium and highly ordered structures can be decreased. This process improvement is attributed to enhanced chain mobility, reduced rod-rod interaction, and decreased rod-coil interaction from the additive. The novel method is based on kinetically facilitating thermodynamic equilibrium. The process requires no modification of polymer structure, indicating that a wide variety of desired polymer functionalities can be designed into BCPs for specific applications.

miR-125b/Ets1 axis regulates transdifferentiation and calcification of vascular smooth muscle cells in a high-phosphate environment.

OBJECTIVES: Vascular calcification is highly prevalent in patients with chronic kidney disease (CKD) and contributes to increased risk of cardiovascular disease and mortality. Accumulated evidences suggested that vascular smooth muscle cells (VSMCs) to osteoblast-like cells transdifferentiation (VOT) plays a crucial role in promoting vascular calcification. MicroRNAs (miRNAs) are a novel class of small RNAs that negatively regulate gene expression via repression of the target mRNAs. In the present work, we sought to determine the role of miRNAs in VSMCs phenotypic transition and calcification induced by ß-glycerophosphoric acid. APPROACH AND RESULTS: Primary cultured rat aortic VSMCs were treated with ß-glycerophosphoric acid for different periods of time. In VSMCs, after ß-glycerophosphoric acid treatment, the expressions of cbf ß1, osteocalcin and osteopontin were significantly increased and SM-22ß expression was decreased. ALP activity was induced by ß-glycerophosphoric acid in a time or dose dependent manner. Calcium deposition was detected in VSMCs incubated with calcification media; then, miR-125b expression was detected by real-time RT PCR. miR-125b expression was significantly decreased in VSMCs after incubated with ß-glycerophosphoric acid. Overexpression of miR-125b could inhibit ß-glycerophosphoric acid-induced osteogenic markers expression and calcification of VSMCs whereas knockdown of miR-125b promoted the phenotypic transition of VSMCs and calcification. Moreover, miR-125b targeted Ets1 and regulated its protein expression in VSMCs. Downregulating Ets1 expression by its siRNA inhibited ß-glycerophosphoric acid-induced the VSMCs phenotypic transition and calcification. CONCLUSION: Our study suggests that down-regulation of miR-125b after ß-glycerophosphoric acid treatment facilitates VSMCs transdifferentiation and calcification through targeting Ets1.

Liquid crystalline epoxy nanocomposite material for dental application.

BACKGROUND/PURPOSE: Novel liquid crystalline epoxy nanocomposites, which exhibit reduced polymerization shrinkage and effectively bond to tooth structures, can be applied in esthetic dentistry, including core and post systems, direct and indirect restorations, and dental brackets. The purposes of this study were to investigate the properties of liquid crystalline epoxy nanocomposites including biocompatibility, microhardness, and frictional forces of bracket-like blocks with different filler contents for further clinical applications. METHODS: In this study, we evaluated liquid crystalline epoxy nanocomposite materials that exhibited various filler contents, by assessing their cell activity performance using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and their microhardness with or without thermocycling. We also evaluated the frictional force between bracket-like duplicates and commercially available esthetic bracket systems using Instron 5566. RESULTS: The liquid crystalline epoxy nanocomposite materials showed good biocompatibility. The materials having high filler content demonstrated greater microhardness compared with commercially available bracket materials, before and after the thermocycling treatment. Thus, manufacturing processes are important to reduce frictional force experienced by orthodontic brackets. CONCLUSION: The microhardness of the bracket-like blocks made by our new material is superior to the commercially available brackets, even after thermocycling. Our results indicate that the evaluated liquid crystalline epoxy nanocomposite materials are of an appropriate quality for application in dental core and post systems and in various restorations. By applying technology to refine manufacturing processes, these new materials could also be used to fabricate esthetic brackets for orthodontic treatment.

Plasmonic nanoparticle-film calipers for rapid and ultrasensitive dimensional and refractometric detection.

In this study, we develop an ultrasensitive nanoparticle (NP)-film caliper that functions with high resolution (angstrom scale) in response to both the dimensions and refractive index of the spacer sandwiched between the NPs and the film. The anisotropy of the plasmonic gap mode in the NP-film caliper can be characterized readily using spectroscopic ellipsometry (SE) without the need for further optical modeling. To the best of our knowledge, this paper is the first to report the use of SE to study the plasmonic gap modes in NP-film calipers and to demonstrate that SE is a robust and convenient method for analyzing NP-film calipers. The high sensitivity of this system originates from the plasmonic gap mode in the NP-film caliper, induced by electromagnetic coupling between the NPs and the film. The refractometric sensitivity of this NP-film caliper reaches up to 314 nm per RIU, which is superior to those of other NP-based sensors. The NP-film caliper also provides high dimensional resolution, down to the angstrom scale. In this study, the shift in wavelength in response to the change in gap spacing is approximately 9 nm Å(-1). Taking advantage of the ultrasensitivity of this NP-film caliper, we develop a platform for discriminating among thiol-containing amino acids.

Block Sequence Effects on the Self-Assembly Behaviors of Polypeptide-Based Penta-Block Copolymer Hydrogels.

Peptide-based hydrogels have great potential for applications in tissue engineering, drug delivery, and so on. We systematically synthesize, characterize, and investigate the self-assembly behaviors of a series of polypeptide-based penta-block copolymers by varying block sequences and lengths. The copolymers contain hydrophobic blocks of poly(γ-benzyl-l-glutamate) (PBG, Bx) and two kinds of hydrophilic blocks, poly(l-lysine) (PLL, Ky) and poly(ethylene glycol) (PEG, EG34), where x and y are the number of repeating units of each block, where PBG and PLL blocks have unique functions for nerve regeneration and cell adhesion. It shows that a sufficient length of the middle hydrophilic segment capped with hydrophobic end PBG blocks is required. They first self-assemble into flower-like micelles and sequentially form transparent hydrogels (as low as 2.3 wt %) with increased polymer concentration. The hydrogels contain a microscale porous structure, a desired property for tissue engineering to facilitate the access of nutrient flow for cell growth and drug delivery systems with high efficiency of drug storage. We hypothesize that the structure of Bx-Ky-EG34-Ky-Bx agglomerates is beyond micron size (transparent), while that of Ky-Bx-EG34-Bx-Ky is on the submicron scale (opaque). We establish a working strategy to synthesize a polypeptide-based block copolymer with a wide window of sol-gel transition. The study offers insight into rational polypeptide hydrogel design with specific morphology, exploring the novel materials as potential candidates for neural tissue engineering.

Conjugated polymer/nanoparticles nanocomposites for high efficient and real-time volatile organic compounds sensors.

The present work demonstrates a high efficient and low cost volatile organic compounds (VOCs) sensor. Nowadays, VOCs, which are typically toxic, explosive, flammable, and an environmental hazard, are extensively used in R&D laboratories and industrial productions. Real-time and accurately monitoring the presence of harmful VOC during the usage, storage, or transport of VOCs is extremely important which protects humans and the environment from exposure in case of an accident and leakage of VOCs. The present work utilizes conducting polymer/nanoparticles blends to sense various VOCs by detecting the variation of optical properties. The novel sensor features high sensitivity, high accuracy, quick response, and very low cost. Furthermore, it is easy to fabricate into a sensing chip and can be equipped anywhere such as a laboratory or a factory where the VOCs are either used or produced and on each joint between transporting pipes or each switch of VOC storage tanks. Real-time sensing is achievable on the basis of the instant response to VOC concentrations of explosive limits. Therefore, an alarm can be delivered within a few minutes for in time remedies. This research starts from investigating fundamental properties, processing adjustments, and a performance test and finally extends to real device fabrication that practically performs the sensing capability. The demonstrated results significantly advance the current sensor technology and are promising in commercial validity in the near future for human and environmental safety concerns against hazardous VOCs.

Dual-Function Fibrous Co-Polypeptide Scaffolds for Neural Tissue Engineering.

This paper reports dual-function (high cell attachment and cell viability) fibrous scaffolds featuring aligned fibers, displaying good biocompatibility and no cytotoxicity. These scaffolds are fabricated through the electrospinning of a co-polypeptide comprising molar equivalents of N6 -carbobenzyloxy-l-lysine and γ-benzyl-l-glutamate, with the lysine moieties enhancing cell adhesion and the neural-stimulating glutamate moieties improving cell viability. These new scaffolds allow neural cells to attach and grow effectively without any special surface treatment or coating. Pheochromocytoma (PC-12) cells grown on these scaffolds exhibit better neuronal activity and longer neurite length, relative to those grown on scaffolds prepared from their respective homo-polypeptides. When the scaffolds are partially hydrolyzed such that they present net positive charge and increased hydrophilicity, the cell viability and neurite growth both increase further. Accordingly, these novel co-polypeptide fibrous scaffolds have potential applications in neural tissue engineering.

Correction: Exploration of biomimetic poly(γ-benzyl-L-glutamate) fibrous scaffolds for corneal nerve regeneration.

Correction for 'Exploration of biomimetic poly(γ-benzyl-L-glutamate) fibrous scaffolds for corneal nerve regeneration' by Tien-Li Ma et al., J. Mater. Chem. B, 2022, 10, 6372-6379, https://doi.org/10.1039/D2TB01250B.

High-Performance Perovskite Solar Cells and Modules Fabricated by Slot-Die Coating with Nontoxic Solvents.

Energy shortage has become a global issue in the twenty-firt century, as energy consumption grows at an alarming rate as the fossil fuel supply exhausts. Perovskite solar cells (PSCs) are a promising photovoltaic technology that has grown quickly in recent years. Its power conversion efficiency (PCE) is comparable to that of traditional silicon-based solar cells, and scale-up costs can be substantially reduced due to its utilization of solution-processable fabrication. Nevertheless, most PSCs research uses hazardous solvents, such as dimethylformamide (DMF) and chlorobenzene (CB), which are not suitable for large-scale ambient operations and industrial production. In this study, we have successfully deposited all of the layers of PSCs, except the top metal electrode, under ambient conditions using a slot-die coating process and nontoxic solvents. The fully slot-die coated PSCs exhibited PCEs of 13.86% and 13.54% in a single device (0.09 cm2) and mini-module (0.75 cm2), respectively.

Eco-friendly plasmonic sensors: using the photothermal effect to prepare metal nanoparticle-containing test papers for highly sensitive colorimetric detection.

Convenient, rapid, and accurate detection of chemical and biomolecules would be a great benefit to medical, pharmaceutical, and environmental sciences. Many chemical and biosensors based on metal nanoparticles (NPs) have been developed. However, as a result of the inconvenience and complexity of most of the current preparation techniques, surface plasmon-based test papers are not as common as, for example, litmus paper, which finds daily use. In this paper, we propose a convenient and practical technique, based on the photothermal effect, to fabricate the plasmonic test paper. This technique is superior to other reported methods for its rapid fabrication time (a few seconds), large-area throughput, selectivity in the positioning of the NPs, and the capability of preparing NP arrays in high density on various paper substrates. In addition to their low cost, portability, flexibility, and biodegradability, plasmonic test paper can be burned after detecting contagious biomolecules, making them safe and eco-friendly.

Synthesis and photocatalytic performance of titanium dioxide nanofibers and the fabrication of flexible composite films from nanofibers.

Titanium dioxide nanofibers were synthesized and applied in flexible composite films that are easy to handle and recycle after use. The nanofibers were obtained in a multi-step procedure. First, sodium titanate nanofibers were prepared from TiO2 nanoparticles through the alkali hydrothermal method. In the next step, sodium hydrogen titanate nanofibers were made by washing the sodium titanate nanofibers in HCl solution. Finally, the sodium hydrogen titanate nanofibers were transformed to TiO2 anatase nanofibers by calcination in air. The photocatalytic activity of TiO2 anatase nanofibers were evaluated and compared to a TiO2 nanoparticle catalyst by decomposing methyl orange dye in aqueous solutions. The achieved reaction rate constant of TiO2 anatase nanofibers was comparable to that of Degussa P25. Paper-like flexible composite films were prepared by co-filtrating aqueous dispersions of TiO2 catalyst materials and cellulose. The composite films made from the nanofibers exhibit better mechanical integrity than those of the nanoparticle-cellulose composites.