Biomineralized Piezoelectrically Active Scaffolds for Inducing Osteogenic Differentiation.

There is an endogenous electric field in living organisms, which plays a vital role in the development and regeneration of bone tissue. Therefore, self-powered piezoelectric material for bone repair has become hot research in recent years. However, the current piezoelectric materials for tissue regeneration still have the shortcomings of lack of biological activity and three-dimensional structure. Here, we proposed a three-dimensional polyurethane foam (PUF) scaffold coated with piezoelectric poly (vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) and modified by a calcium phosphate (CaP) mineralized coating. The preferred scaffold has an open circuit voltage and short circuit current output of 5 V and 200 nA. Combining the physical and chemical properties of the CaP coating, the piezoelectric signal of PVDF-HFP and the three-dimensional structure of PUF, the scaffold exhibits superior promotion of cell osteogenic differentiation and ectopic bone formation in vivo. The mechanism is attributed to an increase in intracellular Ca2+ levels in response to chemical and piezoelectric stimulation with the material. This research not only paves the way for the application of piezoelectric scaffolds to stimulate osteoblasts differentiation in situ, but also lays the foundation for the clinical treatment of long-term osteoporosis.

Shear Flow-Assembled Janus Membrane with Bifunctional Osteogenic and Antibacterial Effects for Guided Bone Regeneration.

Guided bone regeneration (GBR) membranes that reside at the interface between the bone and soft tissues for bone repair attract increasing attention, but currently developed GBR membranes suffer from relatively poor osteogenic and antibacterial effects as well as limited mechanical property and biodegradability. We present here the design and fabrication of a bifunctional Janus GBR membrane based on a shear flow-driven layer by a layer self-assembly approach. The Janus GBR membrane comprises a calcium phosphate-collagen/polyethylene glycol (CaP@COL/PEG) layer and a chitosan/poly(acrylic acid) (CHI/PAA) layer on different sides of a collagen membrane to form a sandwich structure. The membrane exhibits good mechanical stability and tailored biodegradability. It is found that the CaP@COL/PEG layer and CHI/PAA layer contribute to the osteogenic differentiation and antibacterial function, respectively. In comparison with the control group, the Janus GBR membrane displays a 2.52-time and 1.84-time enhancement in respective volume and density of newly generated bone. The greatly improved bone repair ability of the Janus GBR membrane is further confirmed through histological analysis, and it has great potential for practical applications in bone tissue engineering.

Fabrication of large curvature microlens array using confined laser swelling method.

This Letter proposes a confined laser swelling method to fabricate large curvature microlens arrays. Unlike the polymers in conventional free laser swelling, the swelling polymer, which is methyl red-doped polymethyl methacrylate here, is confined between walls formed by a substrate and a flexible cover layer. Because swelling occurs in an enclosed space, decomposed segments remain in the matrix, resulting in a large hump at the side of the flexible cover layer. The results show that these humps are tens of times higher than those acquired by conventional methods and this method has potential for high efficiency large curvature microlens fabrication.

Numerical characterization of electrohydrodynamic micro- or nanopatterning processes based on a phase-field formulation of liquid dielectrophoresis.

The electrohydrodynamic patterning of polymer is a unique technique for micro- and nanostructuring where an electric voltage is applied to an electrode pair consisting of a patterned template and a polymer-coated substrate either in contact or separated by an air gap to actuate the deformation of the rheological polymer. Depending on the template composition, three processes were proposed for implementing the EHDP technique and have received a great amount of attention (i.e., electrostatic force-assisted nanoimprint, dielectrophoresis-electrocapillary force-driven imprint, and electrically induced structure formation). A numerical approach, which is versatile for visualizing the full evolution of micro- or nanostructures in these patterning processes or their variants, is a desirable critical tool for optimizing the process variables in industrial applications of this structuring technique. Considering the fact that all of these processes use a dielectric and viscous polymer (behaving mechanically as a liquid) and are carried out in ambient air, this Article presents a generalized formulation for the numerical characterization of the EHDP processes by coupling liquid dielectrophoresis (L-DEP) and the phase field of the air-liquid dual phase. More importantly, some major scale effects, such as the surface tension, contact angle, liquid-solid interface slip, and non-Newtonian viscosity law are introduced, which can impact the accuracy of the numerical results, as shown experimentally by our electrical actuation of a dielectric microdroplet as a test problem. The numerical results are in good agreement with or are well explained by experimental observations published for the three EHDP processes.

A CD1d-dependent antagonist inhibits the activation of invariant NKT cells and prevents development of allergen-induced airway hyperreactivity.

The prevalence of asthma continues to increase in westernized countries, and optimal treatment remains a significant therapeutic challenge. Recently, CD1d-restricted invariant NKT (iNKT) cells were found to play a critical role in the induction of airway hyperreactivity (AHR) in animal models and are associated with asthma in humans. To test whether iNKT cell-targeted therapy could be used to treat allergen-induced airway disease, mice were sensitized with OVA and treated with di-palmitoyl-phosphatidyl-ethanolamine polyethylene glycol (DPPE-PEG), a CD1d-binding lipid antagonist. A single dose of DPPE-PEG prevented the development of AHR and pulmonary infiltration of lymphocytes upon OVA challenge, but had no effect on the development of OVA-specific Th2 responses. In addition, DPPE-PEG completely prevented the development of AHR after administration of alpha-galactosylceramide (alpha-GalCer) intranasally. Furthermore, we demonstrate that DPPE-PEG acts as antagonist to alpha-GalCer and competes with alpha-GalCer for binding to CD1d. Finally, we show that DPPE-PEG completely inhibits the alpha-GalCer-induced phosphorylation of ERK tyrosine kinase in iNKT cells, suggesting that DPPE-PEG specifically blocks TCR signaling and thus activation of iNKT cells. Because iNKT cells play a critical role in the development of AHR, the inhibition of iNKT activation by DPPE-PEG suggests a novel approach to treat iNKT cell-mediated diseases such as asthma.

Bioactive NAD+ Regeneration Promoted by Multimetallic Nanoparticles Based on Graphene-Polymer Nanolayers.

The concentration of nicotinamide adenine dinucleotide oxidized form (NAD+) changes during aging, and the production of NAD+ can significantly affect both health span and life span. However, it is still of great challenge to regenerate NAD+ from its precursors. Herein, we introduce a method to prepare multimetallic nanoparticles (including Au, Pt, Cu, and MgO) that can efficiently promote the conversion of NADH to NAD+. The nanoparticles are made by mixing reduced graphene oxide-polyethyleneimine-polyacrylic acid nano-films with metallic salts, where four different metal ions are reduced and grow at the surface of the nanolayers. The morphology, size, and growth rate of nanoparticles can be controlled by adding surfactants, applying an electric field, and so forth. Our multimetallic nanoparticles exhibit excellent catalytic performance that a complete conversion of NADH to NAD+ can be finished in 3 min without introducing additional oxygen. This work presents a way for the preparation of multimetallic nanoparticles to promote NAD+ regeneration, which shows great promise for the future design of high-performance materials for antiaging.

Fabrication of concave microlens arrays using controllable dielectrophoretic force in template holes.

This Letter presents a method for fabricating concave microlens arrays of UV-curable polymer by using the dielectrophoresis (DEP) force. The DEP force, generated by a voltage between the patterned conductive template and substrate, acting on the polymer-air interface, can drive the dielectric liquid polymer into the template holes and change the shape of the polymer-air interface. The upper polymer surface of fabricated microlens is super smooth, which can reduce optical noise. The upper surface geometry is measured approximately as parabolic in general, which can lead to a negligible spherical aberration, compared to spherical surfaces.

Developmental expression of solute carrier family 26A member 4 (SLC26A4/pendrin) during amelogenesis in developing rodent teeth.

Ameloblasts need to regulate pH during the formation of enamel crystals, a process that generates protons. Solute carrier family 26A member 4 (SLC26A4, or pendrin) is an anion exchanger for chloride, bicarbonate, iodine, and formate. It is expressed in apical membranes of ion-transporting epithelia in kidney, inner ear, and thyroid where it regulates luminal pH and fluid transport. We hypothesized that maturation ameloblasts express SLC26A4 to neutralize acidification of enamel fluid in forming enamel. In rodents, secretory and maturation ameloblasts were immunopositive for SLC26A4. Staining was particularly strong in apical membranes of maturation ameloblasts facing forming enamel. RT-PCR confirmed the presence of mRNA transcripts for Slc26a4 in enamel organs. SLC26A4 immunostaining was also found in mineralizing connective tissues, including odontoblasts, osteoblasts, osteocytes, osteoclasts, bone lining cells, cellular cementoblasts, and cementocytes. However, Slc26a4-null mutant mice had no overt dental phenotype. The presence of SLC26A4 in apical plasma membranes of maturation ameloblasts is consistent with a potential function as a pH regulator. SLC26A4 does not appear to be critical for ameloblast function and is probably compensated by other pH regulators.

An Electrically Actuated Soft Artificial Muscle Based on a High-Performance Flexible Electrothermal Film and Liquid-Crystal Elastomer.

Liquid-crystal elastomer (LCE)-based soft robots and devices via an electrothermal effect under a low driving voltage have attracted a great deal of attention for their ability on generating larger stress, reversible deformation, and versatile actuation modes. However, electrothermal materials integrated with LCE easily induce the uncertainty of a soft actuator due to the non-uniformity on temperature distribution, inconstant resistance in the deformation process, and slow responsivity after voltage on/off. In this paper, a low-voltage-actuated soft artificial muscle based on LCE and a flexible electrothermal film is presented. At 6.5 V, a saturation temperature of 189 °C can be reached with a heating rate of 21 °C/s, which allows the soft artificial muscle quick and significant contraction and is suitable for untethered operation. Meanwhile, uniform temperature distribution and stable resistance of the flexible electrothermal film in the deformation process are obtained, leading to a work density of 9.97 kJ/m3, an actuating stress of 0.46 MPa, and controllable deformation of the soft artificial muscle. Finally, programmable low-voltage-controlled soft artificial muscles are fabricated by tailoring the flexible electrothermal film or designing structured heating pattern, including a prototype of soft finger-like gripper for transporting small objects, which clearly demonstrates the potential of low-voltage-actuated soft artificial muscles in soft robotics applications.

A self-powered delivery substrate boosts active enzyme delivery in response to human movements.

Stimulated drug releases in response to human movements are highly appealing in medical therapy and various daily uses. However, the design of a mechanically responsive substrate that presents high delivery capacities and can also preserve the activities of sensitive molecules such as enzymes is still challenging. Taking advantage of the recent development in effective piezoelectric flexible films and in molecular delivery devices, we propose a composite delivery substrate that preserves enzyme activities and enhances molecular delivery in response to human movements such as finger presses or massages. The substrate is achieved by combining two parts, which are the energy converting unit and the molecular loading and releasing unit. The energy converting unit is a piezoelectric-dielectric flexible composite film that produces enhanced electricity and preserves the electricity longer compared to a pure piezoelectric polymer. The molecular delivery unit is a layer-by-layer multilayer containing mesoporous silica particles that are assembled at pH 9 but used in neutral solutions. The releases of molecules including small molecules, peptides, and proteins are all accelerated in response to finger presses irrespective of the signs or densities of their charges. More importantly, the enzyme CAT preserves its activity after release from the composite substrates, meaning that the CAT-loaded (PAH/MS)n(PAH/DAS)n@rGO-TFB/PVDF-HFP composite substrate holds promise as a self-powered soothing pad that effectively removes residue H2O2.

Flexible and Transparent Strain Sensors with Embedded Multiwalled Carbon Nanotubes Meshes.

Strain sensors combining high sensitivity with good transparency and flexibility would be of great usefulness in smart wearable/flexible electronics. However, the fabrication of such strain sensors is still challenging. In this study, new strain sensors with embedded multiwalled carbon nanotubes (MWCNTs) meshes in polydimethylsiloxane (PDMS) films were designed and tested. The strain sensors showed elevated optical transparency of up to 87% and high sensitivity with a gauge factor of 1140 at a small strain of 8.75%. The gauge factors of the sensors were also found relatively stable since they did not obviously change after 2000 stretching/releasing cycles. The sensors were tested to detect motion in the human body, such as wrist bending, eye blinking, mouth phonation, and pulse, and the results were shown to be satisfactory. Furthermore, the fabrication of the strain sensor consisting of mechanically blading MWCNTs aqueous dispersions into microtrenches of prestructured PDMS films was straightforward, was low cost, and resulted in high yield. All these features testify to the great potential of these sensors in future real applications.

Combined Photothermal and Surface-Enhanced Raman Spectroscopy Effect from Spiky Noble Metal Nanoparticles Wrapped within Graphene-Polymer Layers: Using Layer-by-layer Modified Reduced Graphene Oxide as Reactive Precursors.

To fabricate functionally integrated hybrid nanoparticles holds high importance in biomedical applications and is still a challenging task. In this study, we report the first reduced graphene oxide (rGO)-nobel metal hybrid particles that present simultaneously the photothermal and surface-enhanced Raman spectroscopy (SERS) effect from the inorganic part and drug loading, dispersibility, and controllability features from LbL polyelectrolyte multilayers. The hybrid particles where spiky noble metal particles were wrapped within rGO-polyelectrolyte layers were prepared by a facile and controllable method. rGO template modified using polyethylenimine (PEI) and poly(acrylic acid) (PAA) via layer-by-layer technology served as the reactive precursors, and the morphologies of the particles could be facilely controlled via controlling the number of bilayers around the rGO template. The hybrid particle presented low cytotoxicity. After loading doxorubicin hydrochloride, the particles effectively induced cell death, and photothermal treatment further decreased cell viability. rGO-Ag hybrid particles could be prepared similarly. We expect the reported method provides an effective strategy to prepare rGO-noble metal hybrid nanoparticles that find potential biomedical applications.

Biomimetic mushroom-shaped microfibers for dry adhesives by electrically induced polymer deformation.

The studies on bioinspired dry adhesion have demonstrated the biomimetic importance of a surface arrayed with mushroom-shaped microfibers among other artificially textured surfaces. The generation of a mushroom-shaped microfiber array with a high aspect ratio and a large tip diameter remains to be investigated. In this paper we report a three-step process for producing mushroom-shaped microfibers with a well-controlled aspect ratio and tip diameter. First, a polymer film coated on an electrically conductive substrate is prestructured into a low-aspect-ratio micropillar array by hot embossing. In the second step, an electrical voltage is applied to an electrode pair composed of the substrate and another conductive planar plate, sandwiching an air clearance. The Maxwell force induced on the air-polymer interface by the electric field electrohydrodynamically pulls the preformed micropillars upward to contact the upper electrode. Finally, the micropillars spread transversely on this electrode due to the electrowetting effect, forming the mushroom tip. In this paper we have demonstrated a polymer surface arrayed with mushroom-shaped microfibers with a large tip diameter (3 times the shaft diameter) and a large aspect ratio (above 10) and provided the testing results for dry adhesion.