In-drop thermal cycling of microcrystal assembly for senescence control (MASC) with minimal variation in efficacy.

The secretome from mesenchymal stem cells (MSCs) has recently gained attention for new therapeutics. However, clinical application requires in vitro cell manufacturing to attain enough cells. Unfortunately, this process often drives MSCs into a senescent state that drastically changes cellular secretion activities. Antioxidants are used to reverse and prevent the propagation of senescence; however, their activity is short-lived. Polymer-stabilized crystallization of antioxidants has been shown to improve bioactivity, but the broad crystal size distribution (CSD) significantly increases the efficacy variation. Efforts were made to crystalize drugs in microdroplets to narrow the CSD, but the fraction of drops containing at least one crystal can be as low as 20%. To this end, this study demonstrates that in-drop thermal cycling of hyaluronic acid-modified antioxidant crystals, named microcrystal assembly for senescence control (MASC), can drive the fraction of microdrops containing crystals to >86% while achieving significantly narrower CSDs (13±3µm) than in bulk (35±11µm). Therefore, this approach considerably improves the practicality of CSD-control in drops. In addition to exhibiting uniform release, MASC made with antioxidizing N-acetylcysteine extended the release time by 40%. MASC further improves the restoration of reactive oxygen species homeostasis in MSCs, thus minimizing cellular senescence and preserving desired secretion activities. We propose that MASC is broadly useful to controlling senescence of a wide array of therapeutic cells during biomanufacturing.

Extending the Bioavailability of Hydrophilic Antioxidants for Metal Ion Detoxification via Crystallization with Polysaccharide Dopamine.

Although metal ions, such as silver and gold, have been shown to have strong antimicrobial properties, their potential to have toxic effects on human and environmental health has gained interest with an improved understanding of their mechanisms to promote oxidative stress. Redox control is a major focus of many drug delivery systems and often incorporates an antioxidant as the active pharmaceutical ingredient (API) to neutralize overproduced reactive oxygen species (ROS). Nevertheless, there are still limitations with bioavailability and extended redox control with regard to antioxidant drug delivery. Herein, this study develops a colloidal antioxidant crystal system that dissolves sustainably through polymer stabilization using sodium hyaluronate conjugated with dopamine (HA-dopa). We explore the role of dopamine incorporation into crystal-stabilizing polymers and quantify the balance between drug-polymer interactions and competing polymer-polymer interactions. We propose that this type of analysis is useful in the engineering of and provides insight into the release behavior of polymer-crystal complexes. In developing our crystal complex, N-acetylcysteine (NAC) was used as the model antioxidant to protect against silver ion toxicity. We found that our optimized HA-dopa-stabilized NAC crystals prolong the release time of NAC 5-fold compared to a polymer-free NAC crystal. Therefore, following sublethal exposure to AgNO3, the extended lifetime of NAC was able to maintain normal intracellular ROS levels, modulate metabolic function, mitigate fluctuations in ATP levels and ATP synthase activity, and preserve contraction frequency in engineered cardiac muscle tissue. Furthermore, the protective effects of the HA-dopa-stabilized NAC crystals were extended to a Daphnia magna model where silver-ion-induced change to both cell-level biochemistry and organ function was alleviated. As such, we propose that the packaging of hydrophilic antioxidants as colloidal crystals drastically extends the lifetime of the API, better maintains ROS homeostasis post metal ion exposure, and therefore preserves both intracellular biochemistry and tissue functionality.

Temperature-Responsive On-Off Control over Water Evaporation Achieved via Sweat-Gland-Mimetic Composites.

Responsive cooling materials that mimic sweat glands have gained popularity because they are efficient and do not require artificial energy sources. Temperature-responsive hydrogels sweat above their volume transition temperature through the release of water and exhibit excellent cooling ability. However, thus far, practical applications have not been possible because the water in these materials cannot be preserved in cool environments. To address this issue, this paper presents a simple composite of poly(N-isopropylacrylamide) and polydimethylsiloxane that offers excellent on-off control over water evaporation and can be used repeatedly; the proposed composite features an evaporation rate of 2.97 g/h above the lower critical solution temperature (LCST) and 0.08 g/h below the LCST. This 35.7-fold change in the water evaporation rate is comparable to that in mammalian sweat glands. The responsive on-off control relies on the structures of the composite and the dry layers formed on the surface of the composite in cool environments. The proposed material effectively regulates water evaporation and offers a novel, low-cost cooling strategy suitable for numerous applications.

Electrothermal soft manipulator enabling safe transport and handling of thin cell/tissue sheets and bioelectronic devices.

"Living" cell sheets or bioelectronic chips have great potentials to improve the quality of diagnostics and therapies. However, handling these thin and delicate materials remains a grand challenge because the external force applied for gripping and releasing can easily deform or damage the materials. This study presents a soft manipulator that can manipulate and transport cell/tissue sheets and ultrathin wearable biosensing devices seamlessly by recapitulating how a cephalopod's suction cup works. The soft manipulator consists of an ultrafast thermo-responsive, microchanneled hydrogel layer with tissue-like softness and an electric heater layer. The electric current to the manipulator drives microchannels of the gel to shrink/expand and results in a pressure change through the microchannels. The manipulator can lift/detach an object within 10 s and can be used repeatedly over 50 times. This soft manipulator would be highly useful for safe and reliable assembly and implantation of therapeutic cell/tissue sheets and biosensing devices.

Stretchable Lithium-Ion Battery Based on Re-entrant Micro-honeycomb Electrodes and Cross-Linked Gel Electrolyte.

Stretchable energy storage devices are of great interest because of their potential applications in body-friendly, skin-like, wearable devices. However, stretchable batteries are very challenging to fabricate. The electrodes must have a degree of stretchability because the active materials occupy most of the volume, and the separator and packaging should also be stretchable. Here, an all-component stretchable lithium-ion battery was realized by leveraging the structural stretchability of re-entrant micro-honeycomb graphene-carbon nanotube (CNT)/active material composite electrodes and a physically cross-linked gel electrolyte, without using an inactive elastomeric substrate or matrix. Active materials interconnected via the entangled CNT and graphene sheets provided a mechanically stable porous network framework, and the inwardly protruding framework in the re-entrant honeycomb structure allowed for structural stretching during deformation. The composite network consisting solely of binder-free, highly conductive materials provided superior electron transfer, and vertically aligned microchannels enabled facile ion transport. Additionally, the physically cross-linked gel electrolyte increased the mechanical stability upon deformation of the electrodes and was effective as a stretchable separator. The resulting stretchable battery showed a high areal capacity of 5.05 mAh·cm-2, superior electrochemical performance up to 50% strain under repeated (up to 500) stretch-release cycles, and long-term stability of 95.7% after 100 cycles in air conditions.

In Situ Incorporation of Pores and Nanoparticles into Polymer Surfaces Using Melt Crystallization.

Engineering the surface properties of a material without affecting its bulk properties is desirable for many applications, but it is often not readily achievable because it requires a complex series of processing steps. This study presents for the first time a simple and straightforward method that can convert regular flat polymer surfaces into various porous composite surfaces. The controlled dissolution of the polymer surface by a dispersion and subsequent melt crystallization allows for the successful embedding of dispersed inorganic or organic particles in the pore walls. The porous surface morphology is not significantly affected by the type of dispersed particle, but the contact and sliding angles and surface wettability are. Both superhydrophobic and oil/water separation surfaces can be conveniently fabricated from flat polymer surfaces. This novel and versatile technique could provide engineering freedom for the future development of various functional materials.

Stimulus-Responsive Anti-Oxidizing Drug Crystals and their Ecological Implication.

Various antioxidants are being used to neutralize the harmful effects of reactive oxygen species (ROS) overproduced in diseased tissues and contaminated environments. Polymer-directed crystallization of antioxidants has attracted attention as a way to control drug efficacy through molecular dissolution. However, most recrystallized antioxidants undertake continuous dissolution independent of the ROS level, thus causing side-effects. This study demonstrates a unique method to assemble antioxidant crystals that modulate their dissolution rate in response to the ROS level. We hypothesized that antioxidants recrystallized using a ROS-labile polymer would be triggered to dissolve when the ROS level increases. We examined this hypothesis by using catechin as a model antioxidant. Catechin was recrystallized using polyethylenimine cross-linked with ROS-labile diselanediylbis-(ethane-2,1-diyl)-diacrylate. Catechin crystallized with the ROS-labile polymer displays accelerated dissolution proportional to the H2 O2 concentration. The ROS-responsive catechin crystals protect vascular cells from oxidative insults by activating intracellular glutathione peroxidase expression and, in turn, inhibiting an increase in the intracellular oxidative stress. In addition, ROS-responsive catechin crystals alleviate changes in the heart rate of Daphnia magna in oxidative media. We propose that the results of this study would be broadly useful for improving the therapeutic efficacy of a broad array of drug compounds.

Spatial Organization of Superparamagnetic Iron Oxide Nanoparticles in/on Nano/Microsized Carriers Modulates the Magnetic Resonance Signal.

Superparamagnetic iron oxide nanoparticles (SPIONs) are often encapsulated into drug-carrying nano/microsized particles for simultaneous magnetic resonance (MR) imaging and treatment of diseased tissues. Unfortunately, encapsulated SPIONs may have a limited ability to modulate the T2-weighted relaxation of water protons, but this insight has not been examined systematically. This study demonstrates that SPIONs immobilized on 200 nm diameter poly(lactic- co-glycolic acid) (PLGA) nanoparticles using Pickering emulsification present 18-fold higher relaxivity than encapsulated SPIONs and 1.5-fold higher relaxivity than free SPIONs. In contrast, the SPIONs immobilized on 10 µm diameter PLGA particles exhibit a minor increase in MR relaxivity. This interesting finding will significantly impact current efforts to synthesize and assemble advanced MR contrast agents.

Enhanced Adhesion of Polydimethylsiloxane Using an Interlocked Finger Structure.

Silicone-based polymers have been widely used for many applications, but their extremely low surface energies and the resulting poor adhesion have been the cause for continuous problems. Herein, a novel adhesion improvement technique using an interlocked finger structure is demonstrated, which enables up to 24.8 and 7.3-fold increases in adhesion compared to the untreated and conventional plasma-treated cases, respectively. The interlocked finger structure is fabricated by surface-confined dissolution and subsequent directional melt crystallization of a solvent. After removing the solvent crystals, porous surfaces are prepared from polyurethane, polyvinyl alcohol, and polystyrene, and these are used to fabricate interfaces of interlocked finger structures with polydimethylsiloxane. The improvement in adhesion strength linearly depends on the pore depth of the prepared surfaces. This novel technique of surface adhesion could improve the performance of polymers with intrinsically poor adhesion in future applications.

2D reentrant auxetic structures of graphene/CNT networks for omnidirectionally stretchable supercapacitors.

Stretchable energy storage systems are essential for the realization of implantable and epidermal electronics. However, high-performance stretchable supercapacitors have received less attention because currently available processing techniques and material structures are too limited to overcome the trade-off relationship among electrical conductivity, ion-accessible surface area, and stretchability of electrodes. Herein, we introduce novel 2D reentrant cellular structures of porous graphene/CNT networks for omnidirectionally stretchable supercapacitor electrodes. Reentrant structures, with inwardly protruded frameworks in porous networks, were fabricated by the radial compression of vertically aligned honeycomb-like rGO/CNT networks, which were prepared by a directional crystallization method. Unlike typical porous graphene structures, the reentrant structure provided structure-assisted stretchability, such as accordion and origami structures, to otherwise unstretchable materials. The 2D reentrant structures of graphene/CNT networks maintained excellent electrical conductivities under biaxial stretching conditions and showed a slightly negative or near-zero Poisson's ratio over a wide strain range because of their structural uniqueness. For practical applications, we fabricated all-solid-state supercapacitors based on 2D auxetic structures. A radial compression process up to 1/10th densified the electrode, significantly increasing the areal and volumetric capacitances of the electrodes. Additionally, vertically aligned graphene/CNT networks provided a plentiful surface area and induced sufficient ion transport pathways for the electrodes. Therefore, they exhibited high gravimetric and areal capacitance values of 152.4 F g-1 and 2.9 F cm-2, respectively, and had an excellent retention ratio of 88% under a biaxial strain of 100%. Auxetic cellular and vertically aligned structures provide a new strategy for the preparation of robust platforms for stretchable energy storage electrodes.

Active Antioxidizing Particles for On-Demand Pressure-Driven Molecular Release.

Overproduced reactive oxygen species (ROS) are closely related to various health problems including inflammation, infection, and cancer. Abnormally high ROS levels can cause serious oxidative damage to biomolecules, cells, and tissues. A series of nano- or microsized particles has been developed to reduce the oxidative stress level by delivering antioxidant drugs. However, most systems are often plagued by slow molecular discharge, driven by diffusion. Herein, this study demonstrates the polymeric particles whose internal pressure can increase upon exposure to H2O2, one of the ROS, and in turn, discharge antioxidants actively. The on-demand pressurized particles are assembled by simultaneously encapsulating water-dispersible manganese oxide (MnO2) nanosheets and green tea derived epigallocatechin gallate (EGCG) molecules into a poly(lactic-co-glycolic acid) (PLGA) spherical shell. In the presence of H2O2, the MnO2 nanosheets in the PLGA particle generate oxygen gas by decomposing H2O2 and increase the internal pressure. The pressurized PLGA particles release antioxidative EGCG actively and, in turn, protect vascular and brain tissues from oxidative damage more effectively than the particles without MnO2 nanosheets. This H2O2 responsive, self-pressurizing particle system would be useful to deliver a wide array of molecular cargos in response to the oxidation level.

Antioxidant and ion-induced gelation functions of pectins enabled by polyphenol conjugation.

The development of antioxidant polymers through the chemical conjugation of natural polyphenols onto polysaccharides has important applications in biomedical, pharmaceutical, food, and cosmetic fields. Due to their labile characteristics, the covalent conjugation of polyphenols while retaining antioxidant properties has been a challenging task. Herein, four structurally different polyphenols, three with and one without a catechol group, were conjugated onto pectin macromolecules via a simple and efficient preparation method involving epichlorohydrin chemistry. The conjugation reactions were confirmed by FT-IR and UV-vis characterization, and the free radical scavenging assay confirmed that the polyphenols maintained their antioxidant activity after the reaction. The conventional structure-antioxidant property relationship can be applied to the assay results, and hesperidin without a catechol group showed the lowest antioxidant capability. The coordination of multivalent metal ions with polyphenols enabled ionic crosslinking and the moduli of hydrogels depend on the type of polyphenols and their molecular interactions with metal ions. The simplicity of preparation and the resulting unique properties could make the pectin conjugates useful in a wide range of application areas.

Biaxial Stretchability and Transparency of Ag Nanowire 2D Mass-Spring Networks Prepared by Floating Compression.

Networks of silver nanowires (Ag NWs) have been considered as promising materials for stretchable and transparent conductors. Despite various improvements of their optoelectronic and electromechanical properties over the past few years, Ag NW networks with a sufficient stretchability in multiple directions that is essential for the accommodation of the multidirectional strains of human movement have seldom been reported. For this paper, biaxially stretchable, transparent conductors were developed based on 2D mass-spring networks of wavy Ag NWs. Inspired by the traditional papermaking process, the 2D wavy networks were produced by floating Ag NW networks on the surface of water and subsequently applying biaxial compression to them. It was demonstrated that this floating-compression process can reduce the friction between the Ag NW-water interfaces, providing a uniform and isotropic in-plane waviness for the networks without buckling or cracking. The resulting Ag NW networks that were transferred onto elastomeric substrates successfully acted as conductors with an excellent transparency, conductivity, and electromechanical stability under a biaxial strain of 30%. The strain sensors that are based on the prepared conductors demonstrated a great potential for the enhanced performances of future wearable devices.

3D Cocontinuous Composites of Hydrophilic and Hydrophobic Soft Materials: High Modulus and Fast Actuation Time.

Hydrogels in nature seldom form a single phase, more often forming structured phases with other soft phases, allowing nature to develop responsive and adaptive strategies. Based on knowledge of how hydrogels are utilized in nature, we developed novel 3D cocontinuous composites from soft materials with extremely different properties, a hydrogel and a silicone. These were successfully prepared by infiltrating liquid polydimethylsiloxane (PDMS) into poly(N-isopropylacrylamide) (PNIPAm) frameworks of aligned pores prepared by directional melt crystallization. The composites had outstanding modulus and swelling ratio compared to other mechanically strong hydrogels. More interestingly, the deswelling kinetics were dramatically accelerated (by a factor of 1000), possibly due to the aligned microchannels and the hydrophobic nature of PDMS. As a result, an actuator movement mimicking flowering could be completed in less than 20 s. This novel and versatile cocontinuous composite strategy could overcome the current limitations of soft materials.

Fabrication of 3D honeycomb-like porous polyurethane-functionalized reduced graphene oxide for detection of dopamine.

A three dimensional reduced graphene oxide/polyurethane (RGO-PU) porous material with connected pores was prepared by physical adsorption of RGO onto the surface of porous PU. The porous PU was prepared by directional melt crystallization of a solvent, which produced high pores with controlled orientation. The prepared RGO-PU was characterized by scanning electron microscopy, spectroscopy and electro-chemical methods. The RGO-PU porous material revealed better electrochemical performance, which might be attributed to the robust structure, superior conductivity, large surface area, and good flexibility. Differential pulse voltammetry (DPV) analysis of DA using the RGO-PU exhibited a linear response range over a wide DA concentration of 100-1150pM, with the detection limit of 1pM. This sensor exhibited outstanding anti-interference ability towards co-existing molecules with good stability, sensitivity, and reproducibility. Furthermore, the fabricated sensor was successfully applied for the quantitative analysis of DA in human serum and urine samples with acceptable recovery, which indicates its feasibility for practical application.

Rupture force of cell adhesion ligand tethers modulates biological activities of a cell-laden hydrogel.

Recent efforts to design a synthetic extracellular matrix for cell culture, engineering, and therapies greatly contributed to addressing biological roles of types and spatial organization of cell adhesion ligands. It is often suggested that ligand-matrix bond strength is another path to regulate cell adhesion and activities; however tools are lacking. To this end, this study demonstrates that a hydrogel coupled with integrin-binding deoxyribonucleic acid (DNA) tethers with pre-defined rupture forces can modulate cell adhesion, differentiation, and secretion activities due to the changes in the number and, likely, force of cells adhered to a gel. The rupture force of DNA tethers was tuned by altering the spatial arrangement of matrix-binding biotin groups. The DNA tethers were immobilized on a hydrogel of alginate grafted with biotin using avidin. Mesenchymal stem cells showed enhanced adhesion, neural differentiation, and paracrine secretion when cultured on the gel coupled with DNA tethers with higher rupture forces. Such innovative cell-matrix interface engineering would be broadly useful for a series of materials used for fundamental and applied studies on biological cells.

Surface tailored PS/TiO2 composite nanofiber membrane for copper removal from water.

Polystyrene (PS)/TiO2 composite nanofiber membranes have been fabricated by electrospinning process for Cu(2+) ions removal from water. The surface properties of the polystyrene nanofibers were modulated by introducing TiO2 nanoparticles. The contact angle of the PS nanofiber membrane was found to be decreased with increasing concentration of TiO2, depicted enhanced hydrophilicity. These membranes were highly effective in adsorbing Cu(2+) ions from water. The adsorption capacity of these membranes was found to be 522 mg/g, which is significantly higher than the results reported by other researchers. This was attributed to enhanced hydrophilicity of the PS/TiO2 composite nanofiber membranes and effective adsorption property of TiO2 nanoparticles.

Reversibly Stretchable, Optically Transparent Radio-Frequency Antennas Based on Wavy Ag Nanowire Networks.

We report a facile approach for producing reversibly stretchable, optically transparent radio-frequency antennas based on wavy Ag nanowire (NW) networks. The wavy configuration of Ag NWs is obtained by floating the NW networks on the surface of water, followed by compression. Stretchable antennas are prepared by transferring the compressed NW networks onto elastomeric substrates. The resulting antennas show excellent performance under mechanical deformation due to the wavy configuration, which allows the release of stress applied to the NWs and an increase in the contact area between NWs. The antennas formed from the wavy NW networks exhibit a smaller return loss and a higher radiation efficiency when strained than the antennas formed from the straight NW networks, as well as an improved stability in cyclic deformation tests. Moreover, the wavy NW antennas require a relatively small quantity of NWs, which leads to low production costs and provides an optical transparency. These results demonstrate the potential of these wavy Ag NW antennas in applications of wireless communications for wearable systems.

In-Situ Formation of Polymer Particles Embedded in Electrospun Fibers via Multi-Nozzle Electrospinning in a Pulsating Instability Regime.

Engineering novel material structures has continually been pursued to further advance modern technologies. These advancements often rely on novel processing technologies. Although many processing parameters have been thoroughly examined in the field of electrospinning, the quasi-steady-state jetting modes are an exception. In this work, we examine the unique structures of polymer particles embedded in water-soluble electrospun fibers, which were successfully prepared via multi-nozzle electrospinning in a pulsating instability mode, without additional emulsifying steps. The aspect ratio of polymer particles can be tailored, based on the concentration of the inner solution, the size of the inner nozzle, and the conductivity of the solution. After dissolving the water-soluble sheath, the polymer particles can easily be dispersed in water and separated from the matrix. This novel electrospinning technology has the potential to open new areas of research such as electrohydrodynamic jetting for drug-delivery systems, sensors, scaffolds, and intelligent coatings.

Floating compression of Ag nanowire networks for effective strain release of stretchable transparent electrodes.

Manipulation of the configuration of Ag nanowire (NW) networks has been pursued to enhance the performance of stretchable transparent electrodes. However, it has remained challenging due to the high Young's modulus and low yield strain of Ag NWs, which lead to their mechanical failure when subjected to structural deformation. We demonstrate that floating a Ag NW network on water and subsequent in-plane compression allows convenient development of a wavy configuration in the Ag NW network, which can release the applied strain. A greatly enhanced electromechanical stability of Ag NW networks can be achieved due to their wavy configuration, while the NW networks maintain the desirable optical and electrical properties. Moreover, the produced NW networks can be transferred to a variety of substrates, offering flexibility for device fabrication. The Ag NW networks with wavy configurations are used as compliant electrodes for dielectric elastomer actuators. The study demonstrates their promising potential to provide improved performance for soft electronic devices.