Rubber-glass nanocomposites fabricated using mixed emulsions.

Many composites consist of matrices of elastomers and nanoparticles of stiff materials. Such composites often have superior properties and are widely used. Embedding elastomers with nanoparticles commonly necessitates intense shear, using machines like extruders and roll millers, which cut polymer chains and degrade properties. Here, we prepare a rubber-glass nanocomposite by using two aqueous emulsions. Each emulsion is separately prepared with a single species of polymer chains. Each polymer chain is copolymerized with a small amount of silane coupling agent. Upon mixing the two emulsions, as water evaporates, the glassy particles retain the shape, and the rubbery particles change shape to form a continuous matrix. Subsequently, the silane coupling agent condensates, which cross-links the rubbery chains and interlinks the rubbery chains to the glassy particles. The cross-links and interlinks stabilize the nanostructure and lead to superior properties. The nanocomposite simultaneously achieves high modulus (~30 MPa), high toughness (~100 kJ m-2), and high fatigue threshold (~1,000 J m-2). The method of mixed emulsion is environmentally friendly and compatible with various open-air manufacturing processes, such as coat, cast, spray, print, and brush. Additionally, the silane coupling agent can interlink the nanocomposite to other materials. The method of mixed emulsion can be used to fabricate objects of complex shapes, fine features, and prescribed spatial variations of compositions.

Conducting Polymer Coatings Prepared by Mixed Emulsions Are Highly Conductive and Stable in Water.

An aqueous emulsion of conducting polymer is commonly applied on a substrate to form a coating after drying. The coating, however, disintegrates in water. This paper reports a coating prepared using a mixture of two emulsions: an aqueous emulsion of conducting polymer, and an aqueous emulsion of hydrophobic and rubbery chains copolymerized with silane coupling agents. When applied on a substrate and dried, particles of the mixed emulsion merge into a continuous film. While the conducting polymer forms percolated nanocrystals, the silane groups crosslink the rubbery chains and interlink the rubbery chains to the substrate. The percolated nanocrystals make the coating highly conductive. The covalent network of hydrophobic polymer chains stabilizes the coating in water. The high conductivity and stability in water may enable broad applications.

3D spatiotemporally scalable in vivo neural probes based on fluorinated elastomers.

Electronic devices for recording neural activity in the nervous system need to be scalable across large spatial and temporal scales while also providing millisecond and single-cell spatiotemporal resolution. However, existing high-resolution neural recording devices cannot achieve simultaneous scalability on both spatial and temporal levels due to a trade-off between sensor density and mechanical flexibility. Here we introduce a three-dimensional (3D) stacking implantable electronic platform, based on perfluorinated dielectric elastomers and tissue-level soft multilayer electrodes, that enables spatiotemporally scalable single-cell neural electrophysiology in the nervous system. Our elastomers exhibit stable dielectric performance for over a year in physiological solutions and are 10,000 times softer than conventional plastic dielectrics. By leveraging these unique characteristics we develop the packaging of lithographed nanometre-thick electrode arrays in a 3D configuration with a cross-sectional density of 7.6 electrodes per 100 µm2. The resulting 3D integrated multilayer soft electrode array retains tissue-level flexibility, reducing chronic immune responses in mouse neural tissues, and demonstrates the ability to reliably track electrical activity in the mouse brain or spinal cord over months without disrupting animal behaviour.

Fatigue-Resistant Polymer Electrolyte Membranes for Fuel Cells.

In a hydrogen fuel cell, an electrolyte membrane conducts protons, but blocks electrons, hydrogen molecules, and oxygen molecules. The fuel cell often runs unsteadily, resulting in fluctuating water production, causing the membrane to swell and contract. The cyclic deformation can cause fatigue crack growth. This paper describes an approach to develop a fatigue-resistant polymer electrolyte membrane. The membrane is prepared by forming an interpenetrating network of a plastic electrolyte and a rubber. The former conducts protons, and the latter enhances fatigue resistance. The introduction of the rubber modestly reduces electrochemical performance, but significantly increases fatigue threshold and lifespan. Compared to pristine plastic electrolyte, Nafion, an interpenetrating network of Nafion and perfluoropolyether (PFPE) reduces the maximum power density by 20%, but increases the fatigue threshold by 175%. Under the wet/dry accelerated stress test, the fuel cell with the Nafion-PFPE membrane has a lifespan 1.7 times that of a fuel cell with the Nafion membrane.

Multiscale stress deconcentration amplifies fatigue resistance of rubber.

Rubbers reinforced with rigid particles are used in high-volume applications, including tyres, dampers, belts and hoses1. Many applications require high modulus to resist excessive deformation and high fatigue threshold to resist crack growth under cyclic load. The particles are known to greatly increase modulus but not fatigue threshold. For example, adding carbon particles to natural rubber increases its modulus by one to two orders of magnitude1-3, but its fatigue threshold, reinforced or not, has remained approximately 100 J m-2 for decades4-7. Here we amplify the fatigue threshold of particle-reinforced rubbers by multiscale stress deconcentration. We synthesize a rubber in which highly entangled long polymers strongly adhere with rigid particles. At a crack tip, stress deconcentrates across two length scales: first through polymers and then through particles. This rubber achieves a fatigue threshold of approximately 1,000 J m-2. Mounts and grippers made of this rubber bear high loads and resist crack growth over repeated operation. Multiscale stress deconcentration expands the space of materials properties, opening doors to curtailing polymer pollution and building high-performance soft machines.

Amphiphilic monomers bridge hydrophobic polymers and water.

Water dissolves a hydrophilic polymer, but not a hydrophobic polymer. Many monomers of hydrophilic polymers, however, are amphiphilic, with a hydrophobic vinyl group for radical polymerization, as well as a hydrophilic group. Consequently, such an amphiphilic monomer may form solutions with both water and hydrophobic polymers. Ternary mixtures of amphiphilic monomer, hydrophobic polymer, and water have recently been used as precursors for interpenetrating polymer networks of hydrophilic polymers and hydrophobic polymers of unusual properties. However, the phase behavior of the ternary mixtures of amphiphilic monomer, hydrophobic polymer, and water themselves has not been studied. Here we mix the amphiphilic monomer acrylic acid, the hydrophobic polymer poly(methyl methacrylate), and water. In the mixture, the hydrophobic polymer can form various morphologies, including solution, micelle, gel, and polymer glass. We interpret these findings by invoking that the hydrophobic and hydrophilic groups of the amphiphilic monomer enable it to function as a bridge. That is, the hydrophobic functional group binds with the hydrophobic polymer, and the hydrophilic functional group binds with water. This picture leads to a simple modification to the Flory-Huggins theory, which agrees well with our experimental data. Amphiphilic monomers offer a rich area for further study for scientific insight, as well as for expanding opportunities to develop materials of self-assembled structures with unusual properties.

Low-intensity mixing process of high molecular weight polymer chains leads to elastomers of long network strands and high fatigue threshold.

Many polymer networks are prepared by crosslinking polymer chains. The polymer chains and crosslinkers are commonly mixed in internal mixers or roll mills. These intense processes break the polymer chains, lower viscosity, and ease mixing. The resulting polymer networks have short chains and a fatigue threshold of ∼100 J m-2. Here, we show that a low-intensity process, a combination of kneading and annealing, preserves long chains, leading to a network of polybutadiene to achieve a fatigue threshold of 440 J m-2. In a network, each chain has multiple crosslinks, which divides the chain into multiple strands. At the ends of the chain are two dangling strands that do not bear the load. The larger the number of crosslinks per chain, the lower the fraction of dangling strands. High fatigue threshold requires long strands, as well as a low fraction of dangling strands. Once intense mixing cuts chains short, each short chain can only have a few crosslinks; the strands are short and the fraction of dangling strands is high-both lower the fatigue threshold. By contrast, a low-intensity mixing process preserves long chains, which can have many crosslinks; the strands are long and the fraction of dangling strands is low-both increase the fatigue threshold. It is hoped that this work will aid the development of fatigue-resistant elastomers.

Hydrogels of arrested phase separation simultaneously achieve high strength and low hysteresis.

Hydrogels are being developed to bear loads. Applications include artificial tendons and muscles, which require high strength to bear loads and low hysteresis to reduce energy loss. However, simultaneously achieving high strength and low hysteresis has been challenging. This challenge is met here by synthesizing hydrogels of arrested phase separation. Such a hydrogel has interpenetrating hydrophilic and hydrophobic networks, which separate into a water-rich phase and a water-poor phase. The two phases arrest at the microscale. The soft hydrophilic phase deconcentrates stress in the strong hydrophobic phase, leading to high strength. The two phases are elastic and adhere through topological entanglements, leading to low hysteresis. For example, a hydrogel of 76 weight % water, made of poly(ethyl acrylate) and poly(acrylic acid), achieves a tensile strength of 6.9 megapascals and a hysteresis of 16.6%. This combination of properties has not been realized among previously existing hydrogels.

Flaw-insensitive fatigue resistance of chemically fixed collagenous soft tissues.

Bovine pericardium (BP) has been used as leaflets of prosthetic heart valves. The leaflets are sutured on metallic stents and can survive 400 million flaps (~10-year life span), unaffected by the suture holes. This flaw-insensitive fatigue resistance is unmatched by synthetic leaflets. We show that the endurance strength of BP under cyclic stretch is insensitive to cuts as long as 1 centimeter, about two orders of magnitude longer than that of a thermoplastic polyurethane (TPU). The flaw-insensitive fatigue resistance of BP results from the high strength of collagen fibers and soft matrix between them. When BP is stretched, the soft matrix enables a collagen fiber to transmit tension over a long length. The energy in the long length dissipates when the fiber breaks. We demonstrate that a BP leaflet greatly outperforms a TPU leaflet. It is hoped that these findings will aid the development of soft materials for flaw-insensitive fatigue resistance.

Making Highly Elastic and Tough Hydrogels from Doughs.

A hydrogel is often fabricated from preexisting polymer chains by covalently crosslinking them into a polymer network. The crosslinks make the hydrogel swell-resistant but brittle. This conflict is resolved here by making a hydrogel from a dough. The dough is formed by mixing long polymer chains with a small amount of water and photoinitiator. The dough is then homogenized by kneading and annealing at elevated temperatures, during which the crowded polymer chains densely entangle. The polymer chains are then sparsely crosslinked into a polymer network under an ultraviolet lamp, and submerged in water to swell to equilibrium. The resulting hydrogel is both swell-resistant and tough. The hydrogel also has near-perfect elasticity, high strength, high fatigue resistance, and low friction. The method is demonstrated with two widely used polymers, poly(ethylene glycol) and cellulose. These hydrogels have never been made swell-resistant, elastic, and tough before. The method is generally applicable to synthetic and natural polymers, and is compatible with industrial processing technologies, opening doors to the development of sustainable, high-performance hydrogels.

Self-assembled nanocomposites of high water content and load-bearing capacity.

Biological tissues, such as cartilage, tendon, ligament, skin, and plant cell wall, simultaneously achieve high water content and high load-bearing capacity. The high water content enables the transport of nutrients and wastes, and the high load-bearing capacity provides structural support for the organisms. These functions are achieved through nanostructures. This biological fact has inspired synthetic mimics, but simultaneously achieving both functions has been challenging. The main difficulty is to construct nanostructures of high load-bearing capacity, characterized by multiple properties, including elastic modulus, strength, toughness, and fatigue threshold. Here we develop a process that self-assembles a nanocomposite using a hydrogel-forming polymer and a glass-forming polymer. The process separates the polymers into a hydrogel phase and a glass phase. The two phases arrest at the nanoscale and are bicontinuous. Submerged in water, the nanocomposite maintains the structure and resists further swelling. We demonstrate the process using commercial polymers, achieving high water content, as well as load-bearing capacity comparable to that of polyethylene. During the process, a rubbery stage exists, enabling us to fabricate objects of complex shapes and fine features. We conduct further experiments to discuss likely molecular origins of arrested phase separation, swell resistance, and ductility. Potential applications of the nanocomposites include artificial tissues, high-pressure filters, low-friction coatings, and solid electrolytes.

Cinobufagin inhibits tumor progression and reduces doxorubicin resistance by enhancing FOXO1-mediated transcription of FCGBP in osteosarcoma.

ETHNOPHARMACOLOGICAL RELEVANCE: Cinobufagin (Huachansu), an aqueous extract from the dried skin of the toad Bufo bufo gargarizans Cantor (frog skin), is a biologically active ingredient of a traditional Chinese medicine cinobufacini that can treat multiple bone pathological conditions such as bone pain, bone tumors, and osteosarcoma. AIM OF THE STUDY: The study aimed to explore the roles and molecular mechanisms of cinobufagin underlying osteosarcoma development and doxorubicin (ADR) resistance. MATERIALS AND METHODS: Cell viability, migration, and invasion were examined by CCK-8, wound healing, and Transwell invasion assays, respectively. RNA sequencing analysis was performed in MNNG/HOS cells treated with or without cinobufagin. The relationships of cinobufagin, forkhead box O1 (FOXO1), and Fc fragment of IgG binding protein (FCGBP) were examined by luciferase reporter, immunofluorescence (IF), RT-qPCR, and chromatin immunoprecipitation (ChIP) assays together with weighted gene co-expression network analysis (WGCNA) analysis. Epithelial-mesenchymal transition (EMT) marker levels were examined through the Western blot assay. The function and molecular basis of cinobufagin in osteosarcoma were further investigated by mouse xenograft experiments. RESULTS: Cinobufagin reduced cell viability, weakened ADR resistance, and inhibited cell migration/invasion/EMT in osteosarcoma cells. Cinobufagin enhanced FOXO1-mediated transcription of downstream genes including FCGBP. FCGBP knockdown partly abrogated the effect of cinobufagin on osteosarcoma cell development. Cinobufagin inhibited the growth of mouse osteosarcoma xenografts in vivo. Cinobufagin reduced the expression of Ki-67 and MMP9 and facilitated caspase-3 expression in osteosarcoma xenografts. CONCLUSION: Cinobufagin suppressed tumor progression and reduced ADR resistance by potentiating FOXO1-mediated transcription of FCGBP in osteosarcoma.

Strain-stiffening seal.

An elastomeric seal needs to be soft to accommodate installation but stiff to block fluid flow. Here we show that the two requirements are better fulfilled by a strain-stiffening elastomer than a neo-Hookean elastomer. We represent the strain-stiffening elastomer using the Gent model, and calculate the deformation in the elastomeric seal using an approach analogous to the lubrication theory of a viscous fluid between rigid walls. We determine the sealing pressure on the basis of two modes of leak. The seal leaks by elastic deformation when the fluid pressure exceeds the contact pressure between the seal and the rigid wall. The seal leaks by rupture when the energy release rate of a crack exceeds the toughness of the elastomer. For both modes of leak, a strain-stiffening elastomer enhances the sealing pressure compared to a neo-Hookean elastomer. We construct diagrams in which the two modes of leak are demarcated. It is hoped that this study will aid in the development of materials and geometries of seals.

Topoarchitected polymer networks expand the space of material properties.

Many living tissues achieve functions through architected constituents with strong adhesion. An Achilles tendon, for example, transmits force, elastically and repeatedly, from a muscle to a bone through staggered alignment of stiff collagen fibrils in a soft proteoglycan matrix. The collagen fibrils align orderly and adhere to the proteoglycan strongly. However, synthesizing architected materials with strong adhesion has been challenging. Here we fabricate architected polymer networks by sequential polymerization and photolithography, and attain adherent interface by topological entanglement. We fabricate tendon-inspired hydrogels by embedding hard blocks in topological entanglement with a soft matrix. The staggered architecture and strong adhesion enable high elastic limit strain and high toughness simultaneously. This combination of attributes is commonly desired in applications, but rarely achieved in synthetic materials. We further demonstrate architected polymer networks of various geometric patterns and material combinations to show the potential for expanding the space of material properties.

Adhesive anastomosis for organ transplantation.

The recent development of tough tissue adhesives has stimulated intense interests among material scientists and medical doctors. However, these adhesives have seldom been tested in clinically demanding surgeries. Here we demonstrate adhesive anastomosis in organ transplantation. Anastomosis is commonly conducted by dense sutures and takes a long time, during which all the vessels are occluded. Prolonged occlusion may damage organs and even cause death. We formulate a tough, biocompatible, bioabsorbable adhesive that can sustain tissue tension and pressurized flow. We expose the endothelial surface of vessels onto a gasket, press two endothelial surfaces to the adhesive using a pair of magnetic rings, and reopen the bloodstream immediately. The time for adhesive anastomosis is shortened compared to the time for sutured anastomosis. We have achieved adhesive anastomosis of a great vein in transplanting the liver of a pig. After the surgery, the adhesive is absorbed, the vein heals, and the pig lives for over one month.

Temperature sensing using junctions between mobile ions and mobile electrons.

Sensing technology is under intense development to enable the Internet of everything and everyone in new and useful ways. Here we demonstrate a method of stretchable and self-powered temperature sensing. The basic sensing element consists of three layers: an electrolyte, a dielectric, and an electrode. The electrolyte/dielectric interface accumulates ions, and the dielectric/electrode interface accumulates electrons (in either excess or deficiency). The ions and electrons at the two interfaces are usually not charge-neutral, and this charge imbalance sets up an ionic cloud in the electrolyte. The design functions as a charged temperature-sensitive capacitor. When temperature changes, the ionic cloud changes thickness, and the electrode changes open-circuit voltage. We demonstrate high sensitivity (∼1 mV/K) and fast response (∼10 ms). Such temperature sensors can be made small, stable, and transparent. Depending on the arrangement of the electrolyte, dielectric, and electrode, we develop four designs for the temperature sensor. In addition, the temperature sensor has good linearity in the range of tens of Kelvin. We further show that the temperature sensors can be integrated into stretchable electronics and soft robots.

Subdural neural interfaces for long-term electrical recording, optical microscopy and magnetic resonance imaging.

Though commonly used, metal electrodes are incompatible with brain tissues, often leading to injury and failure to achieve long-term implantation. Here we report a subdural neural interface of hydrogel functioning as an ionic conductor, and elastomer as a dielectric. We demonstrate that it incurs a far less glial reaction and less cerebrovascular destruction than a metal electrode. Using a cat model, the hydrogel electrode was able to record electrical signals comparably in quality to a metal electrode. The hydrogel-elastomer neural interface also readily facilitated multimodal functions. Both the hydrogel and elastomer are transparent, enabling in vivo optical microscopy. For imaging, cerebral vessels and calcium signals were imaged using two-photon microscopy. The new electrode is compatible with magnetic resonance imaging and does not cause artifact images. Such a new multimodal neural interface could represent immediate opportunity for use in broad areas of application in neuroscience research and clinical neurology.

Posttranscriptional inhibition of γ-adducin promotes the proliferation and migration of osteosarcoma cells.

OBJECTIVE: The expression of cytoskeleton-related protein γ-adducin (ADD3) was abnormally reduced in some tumors. Functional experiments demonstrated that it could inhibit the malignant progression of lung cancer and glioma, whereas the involvement of ADD3 in osteosarcoma was not clear. This study aimed to investigate the role of ADD3 in osteosarcoma and its upstream regulatory mechanisms. METHODS: ADD3 was knocked down by siRNA transfection and the expression level of ADD3 was determined using quantitative real-time PCR assay and Western blot. CCK-8 assay and colony formation were performed to detect the capacity of cell proliferation. Transwell assay and PI and Annexin V-FITC staining were used to determine cell migration and apoptosis, respectively. Luciferase reporter experiment was performed to investigate the interaction between ADD3 and miR-23b-3p. RESULTS: Based on gene silencing assays, we showed that knockdown of ADD3 suppressed apoptosis and promoted the proliferation and migration of osteosarcoma cells, revealing inhibitory effects of ADD3 in osteosarcoma. Luciferase reporter gene assays confirmed that miR-23b-3p could bind to the 3'-UTR of ADD3. Upregulation of miR-23b-3p not only inhibited the expression of ADD3, but also released the tumor suppressive role of ADD3 on the proliferation and migration of osteosarcoma cells. CONCLUSIONS: Our study found that ADD3 functioned as a tumor suppressor gene during osteosarcoma development. The abnormal upregulation of miR-23b-3p targeted the expression of ADD3 and resulted in accelerated osteosarcoma cell proliferation and migration. Thus, the miR-23b-3p/ADD3 axis contributes to the development of osteosarcoma and ADD3 is a key driver of malignancy.

Optoionic Sensing.

The eye converts an optical signal to an ionic signal. This transduction is mimicked here using a photodiode in contact with ionic conductors, such as hydrogels. Photons generate electron-hole pairs in the photodiode. The photodiode/hydrogel interface forms capacitive coupling so that movements of electrons and holes in the photodiode induce movements of ions in the hydrogels. The hydrogels can be readily made stretchable and biocompatible to mimic the function of nerves. When light is turned on and off, the voltage between the hydrogels responds within 10 ms, comparable to the response in the human eye. A photosensitive skin is demonstrated to generate a voltage in response to light but not to stretch. Furthermore, a photosensitive actuation is demonstrated to mimic the light-triggered reflex, such as blinking of the eye and camouflage of the skin. Optoionic transduction has potential applications for wearable devices, implantable devices, and robotics.