Lanthanum-catalysed synthesis of microporous 3D graphene-like carbons in a zeolite template.

Three-dimensional graphene architectures with periodic nanopores­reminiscent of zeolite frameworks­are of topical interest because of the possibility of combining the characteristics of graphene with a three-dimensional porous structure. Lately, the synthesis of such carbons has been approached by using zeolites as templates and small hydrocarbon molecules that can enter the narrow pore apertures. However, pyrolytic carbonization of the hydrocarbons (a necessary step in generating pure carbon) requires high temperatures and results in non-selective carbon deposition outside the pores. Here, we demonstrate that lanthanum ions embedded in zeolite pores can lower the temperature required for the carbonization of ethylene or acetylene. In this way, a graphene-like carbon structure can be selectively formed inside the zeolite template, without carbon being deposited at the external surfaces. X-ray diffraction data from zeolite single crystals after carbonization indicate that electron densities corresponding to carbon atoms are generated along the walls of the zeolite pores. After the zeolite template is removed, the carbon framework exhibits an electrical conductivity that is two orders of magnitude higher than that of amorphous mesoporous carbon. Lanthanum catalysis allows a carbon framework to form in zeolite pores with diameters of less than 1 nanometre; as such, microporous carbon nanostructures can be reproduced with various topologies corresponding to different zeolite pore sizes and shapes. We demonstrate carbon synthesis for large-pore zeolites (FAU, EMT and beta), a one-dimensional medium-pore zeolite (LTL), and even small-pore zeolites (MFI and LTA). The catalytic effect is a common feature of lanthanum, yttrium and calcium, which are all carbide-forming metal elements. We also show that the synthesis can be readily scaled up, which will be important for practical applications such as the production of lithium-ion batteries and zeolite-like catalyst supports.

Biohybrid valveless pump-bot powered by engineered skeletal muscle.

Pumps are critical life-sustaining components for all animals. At the earliest stages of life, the tubular embryonic heart works as a valveless pump capable of generating unidirectional blood flow. Inspired by this elementary pump, we developed an example of a biohybrid valveless pump-bot powered by engineered skeletal muscle. Our pump-bot consists of a soft hydrogel tube connected at both ends to a stiffer polydimethylsiloxane (PDMS) scaffold, creating an impedance mismatch. A contractile muscle ring wraps around the hydrogel tube at an off-center location, squeezing the tube with or without buckling it locally. Cyclic muscle contractions, spontaneous or electrically stimulated, further squeeze the tube, resulting in elastic waves that propagate along the soft tube and get reflected back at the soft/stiff tube boundaries. Asymmetric placement of muscle ring results in a time delay between the wave arrivals, thus establishing a net unidirectional fluid flow irrespective of whether the tube is buckled or not. Flow rates of up to 22.5 µL/min are achieved by the present pump-bot, which are at least three orders of magnitude higher than those from cardiomyocyte-powered valve pumps of similar size. Owning to its simple geometry, robustness, ease of fabrication, and high pumping performance, our pump-bot is particularly well-suited for a wide range of biomedical applications in microfluidics, drug delivery, biomedical devices, cardiovascular pumping system, and more.

Preoperative vascular surgery model using a single polymer tough hydrogel with controllable elastic moduli.

Materials used in organ mimics for medial simulation and education require tissue-like softness, toughness, and hydration to give clinicians and students accurate tactile feedback. However, there is a lack of materials that satisfy these requirements. Herein, we demonstrate that a stretchable and tough polyacrylamide hydrogel is useful to build organ mimics that match softness, crack growth resistance, and interstitial water of real organs. Varying the acrylamide concentration between 29 or 62% w/w with a molar ratio between cross-linker and acrylamide of 1 : 10 800 resulted in a fracture energy around ∼2000 J m-2. More interestingly, this tough gel permitted variation of the elastic modulus from 8 to 62 kPa, which matches the softness of brain to vascular and muscle tissue. According to the rheological frequency sweep, the tough polyacrylamide hydrogels had a greatly decreased number of flow units, indicating that when deformed, stress was dispersed over a greater area. We propose that such molecular dissipation results from the increased number of entangled polymers between distant covalent cross-links. The gel was able to undergo various manipulations including stretching, puncture, delivery through a syringe tip, and suturing, thus enabling the use of the gel as a blood vessel model for microsurgery simulation.

Engineering the Surface of Therapeutic "Living" Cells.

Biological cells are complex living machines that have garnered significant attention for their potential to serve as a new generation of therapeutic and delivery agents. Because of their secretion, differentiation, and homing activities, therapeutic cells have tremendous potential to treat or even cure various diseases and injuries that have defied conventional therapeutic strategies. Therapeutic cells can be systemically or locally transplanted. In addition, with their ability to express receptors that bind specific tissue markers, cells are being studied as nano- or microsized drug carriers capable of targeted transport. Depending on the therapeutic targets, these cells may be clustered to promote intercellular adhesion. Despite some impressive results with preclinical studies, there remain several obstacles to their broader development, such as a limited ability to control their transport, engraftment, secretion and to track them in vivo. Additionally, creating a particular spatial organization of therapeutic cells remains difficult. Efforts have recently emerged to resolve these challenges by engineering cell surfaces with a myriad of bioactive molecules, nanoparticles, and microparticles that, in turn, improve the therapeutic efficacy of cells. This review article assesses the various technologies developed to engineer the cell surfaces. The review ends with future considerations that should be taken into account to further advance the quality of cell surface engineering.

Pore Diameter of Mesoporous Silica Modulates Oxidation of H2O2-Sensing Chromophore in a Porous Matrix.

Hydrogen peroxide (H2O2) is an attractive chemical because of its bleaching properties in paper and pulp industry and as a disinfectant in the food, water, and medical industries. However, it is important to monitor the residual H2O2 level after its usage and prevent any unintended health problems or chemical reactions. Most H2O2 sensors often utilize fluorophores or electrical circuitry that requires an additional irradiation or a digital display. To this end, this study presents a 3,3',5,5'-tetramethylbenzidine (TMB)/horseradish peroxidase (HRP)-loaded patch that alerts the presence of high H2O2 levels by generating a visible blue color. We hypothesized that water-insoluble TMB immobilized within mesoporous silica particles of proper pore diameter and structure would act as a colorimetric indicator through the H2O2-mediated oxidation within a cross-linked patch. We examined this hypothesis by immobilizing TMB molecules in mesoporous silica particles with 2 and 7 nm diameter cylindrical pores as well as on nonporous silica particles. Then, we loaded these TMB-silica particles and HRP in a porous alginate patch via sequential in situ cross-linking reaction and lyophilization. In the presence of 25-5000 µM H2O2, which simulate H2O2 concentrations found in residual disinfecting fluids, the patch loaded with TMB-mesoporous silica particles with 7 nm diameter pores generated a distinct blue color with varying intensities depending on the H2O2 concentration. The design principles demonstrated in this study should be applicable to a broad array of sensors to be integrated into a moldable, three-dimensional matrix.

Non-Topotactic Transformation of Silicate Nanolayers into Mesostructured MFI Zeolite Frameworks During Crystallization.

Mesostructured MFI zeolite nanosheets are established to crystallize non-topotactically through a nanolayered silicate intermediate during hydrothermal synthesis. Solid-state 2D NMR analyses, with sensitivity enhanced by dynamic nuclear polarization (DNP), provide direct evidence of shared covalent 29 Si-O-29 Si bonds between intermediate nanolayered silicate moieties and the crystallizing MFI zeolite nanosheet framework.

Co-development of crystalline and mesoscopic order in mesostructured zeolite nanosheets.

Mesoporous zeolites are a new and technologically important class of materials that exhibit improved diffusion and catalytic reaction properties compared to conventional zeolites with sub-nanometer pore dimensions. During their syntheses, the transient developments of crystalline and mesoscopic order are closely coupled and challenging to control. Correlated solid-state NMR, X-ray, and electron microscopy analyses yield new molecular-level insights on the interactions and distributions of complicated organic structure-directing agents with respect to crystallizing zeolite frameworks. The analyses reveal the formation of an intermediate layered silicate phase, which subsequently transforms into zeolite nanosheets with uniform nano- and mesoscale porosities. Such materials result from coupled surfactant self-assembly and inorganic crystallization processes, the interplay between which governs the onset and development of framework structural order on different length and time scales.

Random-graft polymer-directed synthesis of inorganic mesostructures with ultrathin frameworks.

A widely employed route for synthesizing mesostructured materials is the use of surfactant micelles or amphiphilic block copolymers as structure-directing agents. A versatile synthesis method is described for mesostructured materials composed of ultrathin inorganic frameworks using amorphous linear-chain polymers functionalized with a random distribution of side groups that can participate in inorganic crystallization. Tight binding of the side groups with inorganic species enforces strain in the polymer backbones, limiting the crystallization to the ultrathin micellar scale. This method is demonstrated for a variety of materials, such as hierarchically nanoporous zeolites, their aluminophosphate analogue, TiO2 nanosheets of sub-nanometer thickness, and mesoporous TiO2, SnO2, and ZrO2. This polymer-directed synthesis is expected to widen our accessibility to unexplored mesostructured materials in a simple and mass-producible manner.

Microporous aluminophosphate nanosheets and their nanomorphic zeolite analogues tailored by hierarchical structure-directing amines.

Multiamines with amphiphilic structures have been synthesized to serve as simultaneous structure-directing agents in micro- and meso-structural levels for aluminophosphate materials (AlPOs) and their analogues, such as silicoaluminophosphate, cobalt aluminophosphate, and gallium phosphate. The amine molecules are assembled into a micelle with a specific morphology to function as a meso-level structure director. Individual amine groups in the micelle are able to direct the formation of microporous crystalline AlPO structure. The resultant meso-level morphologies of the AlPOs are typically nanosheets of uniform thickness, which can be tailored in the range of 2-5 nm by the number of amine groups. Sponge-like disordered mesoporous morphologies can be generated, depending on the amine structures. Using such multiamines provides a versatile route to various phosphate materials with a structural hierarchy for enhanced porous functionalities.

Manganese Oxide Nanozyme-Doped Diatom for Safe and Efficient Treatment of Peri-Implantitis.

Peri-implantitis is a major cause of dental implant failure. Bacterial biofilm contamination on the implant induces surrounding bone resorption and soft tissue inflammation, leading to severe deterioration of oral health. However, conventional biofilm removal procedures, such as mechanical decontamination and antiseptic application, are not effective enough to induce reosseointegration on decontaminated implant surfaces. This is due to (1) incomplete decontamination of the biofilm from inaccessible areas and (2) physicochemical alteration of implant surfaces caused by decontamination procedures. Herein, a safe and effective therapeutic approach for peri-implantitis is developed, which involves decontamination of implant-bound biofilms using the kinetic energy of microsized oxygen bubbles generated from the catalytic reaction between hydrogen peroxide (H2O2) and manganese oxide (MnO2) nanozyme sheet-doped silica diatom microparticles (Diatom Microbubbler, DM). Rapidly moving microsized DM particles are able to penetrate narrow spaces between implant screws, exerting just the right amount of force to entirely destroy biofilms without harming the surrounding mucosa or implant surfaces, as opposed to conventional antiseptics such as chlorhexidine or 3% H2O2 when used alone. Consequently, decontamination with DM facilitates successful reosseointegration on the peri-implantitis-affected implant surface. In summary, our new DM-based therapeutic approach will become a promising alternative to resolve clinically challenging aspects of peri-implantitis.

Transparent and Flexible Electronics Assembled with Metallic Nanowire-Layered Nondrying Glycerogel.

There has been increasing demand for transparent and mechanically durable electrical conductors for their uses in wearable electronic devices. It is common to layer metallic nanowires on transparent but stiff poly(dimethylsiloxane) (PDMS) or stretchable but opaque Ecoflex-based substrates. Here, we hypothesized that layering metallic nanowires on a stretchable and hygroscopic gel would allow us to assemble a transparent, stretchable, and durable conductor. The hygroscopic property of the gel was attained by partially replacing water in the preformed polyacrylamide hydrogel with glycerol. The resulting gel, denoted as a glycerogel, could remain hydrated for over 6 months in air by taking up water molecules from the air. The glycerogel was tailored to be stretchable up to 8 times its original length by tuning the amount of the cross-linker and acrylamide. The resulting glycerogel allowed for deposition of wavy silver nanowires using the prestrain method up to 400% prestrain, without causing kinks and interfacial cracks often found with nanowires layered onto PDMS. With a prestrain of 100%, the resulting nanowire-gel conductor exhibited optical transparency (85%) and electrical conductivity (17.1 ohm/sq) even after 5000 cycles of deformation. The results of this study would broadly be useful to improve the performance of the next generation of flexible electronic devices.

Catalytic microgelators for decoupled control of gelation rate and rigidity of the biological gels.

Fibrin gels have been extensively used for three-dimensional cell culture, bleeding control, and molecular and cell therapies because the fibrous networks facilitate biomolecular and cell transport. However, a small window for gelation makes it difficult to handle the gels for desired preparation and transport. Several methods developed to control gelation rates often alter the microstructure, thereby affecting the mechanical response. We hypothesized that a particle designed to discharge thrombin cargos in response to an external stimulus, such as H2O2, would provide control of the gelation rate over a broad range while strengthening the gel. We examined this hypothesis by assembling poly (lactic-co-glycolic acid) (PLGA) particles loaded with thrombin and MnO2 nanosheets that decompose H2O2 to O2 gas. The resulting particles named as catalytic microgelator were mixed with fibrinogen solution or blood containing 0.2mM H2O2. Due to the increased internal pressure, these particles released a 3-fold larger mass of thrombin than PLGA particles loaded only with thrombin. As a consequence, catalytic microgelators increased the gelation time by one order of magnitude and the elastic modulus by a factor of two compared with the fibrin gel formed by directly mixing fibrinogen and thrombin in solution. These catalytic microgelators also served to clot blood, unlike PLGA particles loaded with thrombin. The resulting blood clot was also more rigid than the blood clot formed by thrombin solution. The results of this study would serve as a new paradigm in controlling gelation kinetics of pre-gel solution and mechanical properties of the post-gel matrix.

Surface tethering of stem cells with H2O2-responsive anti-oxidizing colloidal particles for protection against oxidation-induced death.

Mesenchymal stem cells are the new generation of medicine for treating numerous vascular diseases and tissue defects because of their ability to secrete therapeutic factors. Poor cellular survival in an oxidative diseased tissue, however, hinders the therapeutic efficacy. To this end, we hypothesized that tethering the surface of stem cells with colloidal particles capable of discharging antioxidant cargos in response to elevated levels of hydrogen peroxide (H2O2) would maintain survival and therapeutic activity of the stem cells. We examined this hypothesis by encapsulating epigallocatechin gallate (EGCG) and manganese oxide (MnO2) nanocatalysts into particles comprising poly(d,l-lactide-co-glycolide)-block-hyaluronic acid. The MnO2 nanocatalysts catalyzed the decomposition of H2O2 into oxygen gas, which increased the internal pressure of particles and accelerated the release of EGCG by 1.5-fold. Consequently, stem cells exhibited 1.2-fold higher metabolic activity and 2.8-fold higher secretion level of pro-angiogenic factor in sub-lethal H2O2 concentrations. These stem cells, in turn, performed a greater angiogenic potential with doubled number of newly formed mature blood vessels. We envisage that the results of this study will contribute to improving the therapeutic efficacy of a wide array of stem cells.

Stretchable, anti-bacterial hydrogel activated by large mechanical deformation.

Hydrogels have been used extensively to deliver functional molecular cargos in response to external mechanical force. However, the intrinsic brittleness of gels restricts the applicable range of strain to 0.1, thus limiting the range of molecular release rate that may be controlled. Also, uncontrollable molecular diffusion, which is especially prominent in small molecules, reduces the role of mechanical stimulus on the release rate. As such, we hypothesized that these challenges would be resolved by combining cyclodextrin, which may form guest-host complexes with small molecular cargos, with a stretchable hydrogel system. We examined this hypothesis by synthesizing cyclodextrin acrylate and incorporating it into a polyacrylamide gel that can be stretched by 100% of its original length. In the absence of external stretching, hydrogels containing cyclodextrin acrylate with a degree of acryloyl group substitution (DSA) of 2.3 presented a lower molecular release rate than hydrogels without cyclodextrin acrylate. More interestingly, the polyacrylamide-cyclodextrin hydrogel system displayed an increased molecular release rate corresponding to the degree of stretching, particularly in the gels containing cyclodextrin acrylate with a DSA of 2.3. As such, this stretchable gel loaded with quinine was used to inhibit the growth of E. coli in lysogeny broth only when the gel was stretched. We believe the results of this study would be valuable for improving the quality of controlled molecular delivery and subsequent efficacy of molecular cargos.

Diatom Microbubbler for Active Biofilm Removal in Confined Spaces.

Bacterial biofilms form on and within many living tissues, medical devices, and engineered materials, threatening human health and sustainability. Removing biofilms remains a grand challenge despite tremendous efforts made so far, particularly when they are formed in confined spaces. One primary cause is the limited transport of antibacterial agents into extracellular polymeric substances (EPS) of the biofilm. In this study, we hypothesized that a microparticle engineered to be self-locomotive with microbubbles would clean a structure fouled by biofilm by fracturing the EPS and subsequently improving transports of the antiseptic reagent. We examined this hypothesis by doping a hollow cylinder-shaped diatom biosilica with manganese oxide (MnO2) nanosheets. In an antiseptic H2O2 solution, the diatoms doped by MnO2 nanosheets, denoted as diatom bubbler, discharged oxygen gas bubbles continuously and became self-motile. Subsequently, the diatoms infiltrated the bacterial biofilm formed on either flat or microgrooved silicon substrates and continued to generate microbubbles. The resulting microbubbles merged and converted surface energy to mechanical energy high enough to fracture the matrix of biofilm. Consequently, H2O2 molecules diffused into the biofilm and killed most bacterial cells. Overall, this study provides a unique and powerful tool that can significantly impact current efforts to clean a wide array of biofouled products and devices.

Proangiogenic alginate-g-pyrrole hydrogel with decoupled control of mechanical rigidity and electrically conductivity.

BACKGROUND: An electrically conductive hydrogel has emerged to regulate cellular secretion activities with electrical stimulation. However, the electrical conductivity of typical hydrogel systems decreases with increasing elastic modulus of the hydrogels because of decreased transport of ions through a polymeric cross-linked mesh. METHOD: This study hypothesized that the inverse dependency between electrical conductivity and elastic modulus would be made through the cross-linking of conductive monomer-units conjugated to a hydrophilic polymeric backbone. This hypothesis was examined through the cross-linking of pyrrole groups that were conjugated to an alginate backbone, termed alginate-g-pyrrole. RESULTS: Hydrogels with increased degrees of pyrrole substitution exhibited a simultaneous increase in the gels mechanical rigidity and electrical conductivity. The resulting hydrogel could control the adhesion and vascular endothelial growth factor secretion of cells via applied electrical stimulation. CONCLUSIONS: This material design principle will be broadly useful to fabricating materials used for various actuation, cell culture, and biomedical applications.

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.

Damage, Healing, and Remodeling in Optogenetic Skeletal Muscle Bioactuators.

A deeper understanding of biological materials and the design principles that govern them, combined with the enabling technology of 3D printing, has given rise to the idea of "building with biology." Using these materials and tools, bio-hybrid robots or bio-bots, which adaptively sense and respond to their environment, can be manufactured. Skeletal muscle bioactuators are developed to power these bio-bots, and an approach is presented to make them dynamically responsive to changing environmental loads and robustly resilient to induced damage. Specifically, since the predominant cause of skeletal muscle loss of function is mechanical damage, the underlying mechanisms of damage are investigated in vitro, and an in vivo inspired healing strategy is developed to counteract this damage. The protocol that is developed yields complete recovery of healthy tissue functionality within two days of damage, setting the stage for a more robust, resilient, and adaptive bioactuator technology than previously demonstrated. Understanding and exploiting the adaptive response behaviors inherent within biological systems in this manner is a crucial step forward in designing bio-hybrid machines that are broadly applicable to grand engineering challenges.