Flexible Electronics Based on Organic Semiconductors: from Patterned Assembly to Integrated Applications.

Organic flexible electronic devices are at the forefront of the electronics as they possess the potential to bring about a major lifestyle revolution owing to outstanding properties of organic semiconductors, including solution processability, lightweight and flexibility. For the integration of organic flexible electronics, the precise patterning and ordered assembly of organic semiconductors have attracted wide attention and gained rapid developments, which not only reduces the charge crosstalk between adjacent devices, but also enhances device uniformity and reproducibility. This review focuses on recent advances in the design, patterned assembly of organic semiconductors, and flexible electronic devices, especially for flexible organic field-effect transistors (FOFETs) and their multifunctional applications. First, typical organic semiconductor materials and material design methods are introduced. Based on these organic materials with not only superior mechanical properties but also high carrier mobility, patterned assembly strategies on flexible substrates, including one-step and two-step approaches are discussed. Advanced applications of flexible electronic devices based on organic semiconductor patterns are then highlighted. Finally, future challenges and possible directions in the field to motivate the development of the next generation of flexible electronics are proposed.

Oral Administration of Starting Materials for In Vivo Synthesis of Antibacterial Gold Nanoparticles for Curing Remote Infections.

Oral administration is a facile and safe way for medication. However, most of the reported nanomedicines could not be taken orally, partially due to their unsatisfied stability, poor absorbance, or toxicity in the gastrointestinal tract. Here, we demonstrate that we could robustly synthesize gold nanoparticles (GNPs) in vivo by orally administering two starting materials, tetrachloroauric acid and aminophenyl boronic acid (ABA). The ABA-activated GNPs (A-GNPs) synthesized in vivo could be absorbed by the gastrointestinal tract and reach the remote infection lesions such as peritonitis caused by multidrug resistant (MDR) bacteria in mice. The A-GNPs exhibit excellent antibacterial efficacy (MIC, 3 µg/mL), long half-life (16-17 h), effective clearance (residual concentration is near 0 within 72 h), and high biosafety (safe dose/effective dose, 8 times). Our study is a pioneering attempt for synthesizing and taking nanomedicines orally just like preparing and drinking a cocktail.

The Density of Surface Coating Can Contribute to Different Antibacterial Activities of Gold Nanoparticles.

With the widespread use of antibiotics, the number of complex infection cases caused by unknown pathogens is increasing and novel antibiotics with tunable antibacterial spectra and low toxicity are highly desirable. Herein, we report that, by selecting thiol or amine, two groups with different binding affinities with gold, as anchoring groups, phenylboronic acid can be decorated on gold nanoparticles (AuNPs) with different densities, which contributes to Gram-selective antibacterial activities of the AuNPs. The AuNPs modified with amine- or thiol-tethered phenylboronic acids specifically bind to lipopolysaccharide (LPS, Gram-negative) or lipoteichoic acid (LTA, Gram-positive), respectively. By modifying AuNPs with different ratios of thiol- and amine-tethered phenylboronic acids, the resulting AuNPs show potent and tunable antibacterial activity. The AuNP-based antibacterial agents with optional Gram selectivity are promising for applications in personalized therapy.

Activating the Antibacterial Effect of 4,6-Diamino-2-pyrimidinethiol-Modified Gold Nanoparticles by Reducing their Sizes.

Adequately decorated gold nanoparticles (GNPs) have excellent antibiotic activities against multidrug-resistant (MDR) bacteria. Nanoparticles exhibiting Gram selective antibacterial actions are beneficial to precise therapy. Here, we present a strategy to tune the antibacterial spectrum of a small molecule (4,6-diamino-2-pyrimidinethiol, DAPT)-modified GNPs (DAPT-GNPs, DGNPs) by adjusting their sizes. Compared to large (ca. 14 nm diameter) DGNPs (lDGNPs) and medium-sized (3-4 nm diameter) DGNPs (mDGNPs), which have no antibacterial effect or only target Gram-negative (G-) bacteria, ultrasmall DGNPs (uDGNPs, <2 nm) have a broad antibacterial spectrum, especially showing an over 60-fold increase in antibacterial efficacy against Gram-positive (G+) bacteria. Moreover, the uDGNPs-functionalized scaffolds (agarose gel) can serve as general wound dressings for healing burnt infections. Our strategy is insightful for exploring properties of the nanomaterials and their applications.

Reverse Reconstruction and Bioprinting of Bacterial Cellulose-Based Functional Total Intervertebral Disc for Therapeutic Implantation.

The degradation of intervertebral discs (IVD), a typical hierarchical structured tissue, causes serious neck and back pain. The current methods cannot fully reconstitute the unique structure and function of native IVD. In this study, by reverse reconstruction of the structure of native IVD and bioprinting bacterial cellulose (BC) nanofibers with a high-throughput optimized micropattern screening microchip, a total IVD is created that contained type II collagen-based nucleus pulposus (NP) and hierarchically organized and micropatterned BC-based annulus fibrosus (AF), mimicking native IVD tissue. The artificial NP contains rat NP cells, whereas the AF contains concentrically arranged BC layers with aligned micropatterns and attached AF cells in +/-30° alternate directions between adjacent layers. Long-term (3 months) implantation experiments on rats demonstrate the excellent structural (shape maintenance, hydration, tissue integration) and functional (mechanical support and flexibility) performance of the artificial IVD. This study provides a novel strategy for creating highly sophisticated artificial tissues.

Gold Nanoclusters for Targeting Methicillin-Resistant Staphylococcus†aureus In†Vivo.

Widespread multidrug resistance caused by the abuse of antibiotics calls for novel strategies and materials. Gold nanoclusters (AuNCs) are scarcely explored for combating multidrug-resistant (MDR) bacteria in vivo. We herein synthesized a novel class of AuNCs, namely quaternary ammonium (QA) capped AuNCs (QA-AuNCs) as potent antibiotics selectively targeting MDR Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE), in vivo. QA-AuNCs kill bacteria through a combined physicochemical mechanism, and show excellent therapeutic effects in both a skin infection model and a bacteremia model induced by MRSA. In addition, owing to their intense fluorescence, QA-AuNCs can be used for the discrimination of live/dead bacteria and bacteria counting, suggesting their potential for clinical theranostics.

Microstructured Multilevel Bacterial Cellulose Allows the Guided Growth of Neural Stem Cells.

Repeated photolithographic and etching processes allow the production of multileveled polymer microstructures that can be used as templates to produce bacterial cellulose with defined surfaces on demand. By applying this approach, the bacterial cellulose surface obtains new properties and its use for culturing neural stem cells cellulose substrate topography influences the cell growth in a defined manner.

Multi-Interfacial Confined Assembly of Colloidal Quantum Dots Quasisuperlattice Microcavities for High-Resolution Full-Color Microlaser Arrays.

Colloidal quantum dots (CQDs) are considered a promising material for the next generation of integrated display devices due to their designable optical bandgap and low energy consumption. Owing to their dispersibility in solvents, CQD micro/nanostructures are generally fabricated by solution-processing methods. However, the random mass transfer in liquid restricts the programmable construction in macroscopy and ordered assembly in microscopy for the integration of CQD optical structures. Herein, a multi-interfacial confined assembly strategy is developed to fabricate CQDs programmable microstructure arrays with a quasisuperlattice configuration through controlling the dynamics of three-phase contact lines (TPCLs). The motion of TPCLs dominates the division of liquid film for precise positioning of CQD microstructures, while pinned TPCLs control the solvent evaporation and concentration gradient to directionally drive the mass transfer and packing of CQDs. Owing to their long-range order and adjustable structural dimensions, CQD microring arrays function as high-quality-factor (high-Q) lasing resonant cavities with low thresholds and tunable lasing emission modes. Through the further surface treatment and liquid dynamics control, the on-chip integration of red (R), green (G), and blue (B) multicomponent CQD microlaser arrays are demonstrated. The technique establishes a new route to fabricate large-area, ultrahigh-definition, and full-color CQD laser displays.

Wafer-scale integration of stretchable semiconducting polymer microstructures via capillary gradient.

Organic semiconducting polymers have opened a new paradigm for soft electronics due to their intrinsic flexibility and solution processibility. However, the contradiction between the mechanical stretchability and electronic performances restricts the implementation of high-mobility polymers with rigid molecular backbone in deformable devices. Here, we report the realization of high mobility and stretchability on curvilinear polymer microstructures fabricated by capillary-gradient assembly method. Curvilinear polymer microstructure arrays are fabricated with highly ordered molecular packing, controllable pattern, and wafer-scale homogeneity, leading to hole mobilities of 4.3 and 2.6 cm2 V-1 s-1 under zero and 100% strain, respectively. Fully stretchable field-effect transistors and logic circuits can be integrated in solution process. Long-range homogeneity is demonstrated with the narrow distribution of height, width, mobility, on-off ratio and threshold voltage across a four-inch wafer. This solution-assembly method provides a platform for wafer-scale and reproducible integration of high-performance soft electronic devices and circuits based on organic semiconductors.

Mercaptophenylboronic Acid-Activated Gold Nanoparticles as Nanoantibiotics against Multidrug-Resistant Bacteria.

Multidrug-resistant (MDR) bacteria-induced infections are becoming challenging issues threatening human health and life. Current antibiotics can hardly tackle this problem. Herein, we present a strategy to prepare mercaptophenylboronic acid (MBA)-activated gold nanoparticles (Au NPs) as an antibacterial agent against MDR bacteria. Both Au NPs and MBA cannot serve as antibiotics. However, when MBA attaches on Au NPs, the Au_MBA NPs show potent antibacterial activities against Gram-positive MDR clinical isolates (e.g., MDR Staphyloccocus aureus, MDR S. aureus; MDR Staphyloccocus epidermidis, MDR S. epidermidis). Furthermore, Au_MBA NPs show an extremely high median lethal dose (LD50,i.v., 960 mg/kg), which is much higher than those of most of the clinically used antibiotics. As an application example, we dope Au_MBA NPs with electrospun poly(ε-caprolactone) (PCL)/gelatin nanofibrous membranes as wound dressings, which show striking ability to remedy S. aureus- or MDR S. aureus-infected full-thickness skin wounds on rats. Our study provides a novel strategy for treating MDR bacteria-infected wounds in a simple, low-cost, and efficient way, which holds promise for broad clinical applications.

Silk sericin-enhanced microstructured bacterial cellulose as tissue engineering scaffold towards prospective gut repair.

As a first step towards the production of functional cell sheets applicable for the regeneration of gut muscle layer, microstructured bacterial cellulose (mBC) was assessed for its ability to support the growth of enteric nervous system (ENS) and gut smooth muscle cells (SMCs). To improve the cellular response, mBC was modified with silk sericin (SS) which has renowned abilities in supporting tissue regeneration. While SS did not impair the line structures imparted to BC by PDMS templates, similarly to the patterns, it affected its physical properties, ultimately leading to variations in the behavior of cells cultured onto these substrates. Enabled by the stripes on mBC, both SMCs and ENS cells were aligned in vitro, presenting the in vivo-like morphology essential for peristalsis and gut function. Interestingly, cell growth and differentiation remarkably enhanced upon SS addition to the samples, indicating the promise of the mBC-SS constructs as biomaterial not only for gut engineering, but also for tissues where cellular alignment is required for function, namely the heart, blood vessels, and similars.

A Strategy for Rapid Construction of Blood Vessel-Like Structures with Complex Cell Alignments.

A method is developed that can rapidly produce blood vessel-like structures by bonding cell-laden electrospinning (ES) films layer by layer using fibrin glue within 90 min. This strategy allows control of cell type, cell orientation, and material composition in separate layers. Furthermore, ES films with thicker fibers (polylactic-co-glycolic acid, fiber diameter: ≈3.7 µm) are used as cell-seeding layers to facilitate the cell in-growth; those with thinner fibers (polylactic acid, fiber diameter: ≈1.8 µm) are used as outer reinforcing layers to improve the mechanical strength and reduce the liquid leakage of the scaffold. Cells grow, proliferate, and migrate well in the multilayered structure. This design aims at a new type of blood vessel substitute with flexible control of parameters and implementation of functions.

Bread-derived 3D macroporous carbon foams as high performance free-standing anode in microbial fuel cells.

Microbial fuel cells (MFCs) are a promising clean energy source to directly convert waste chemicals to available electric power. However, the practical application of MFCs needs the increased power density, enhanced energy conversion efficiency and reduced electrode material cost. In this study, three-dimensional (3D) macroporous N, P and S co-doped carbon foams (NPS-CFs) were prepared by direct pyrolysis of the commercial bread and employed as free-standing anodes in MFCs. As-obtained NPS-CFs have a large specific surface area (295.07 m2 g-1), high N, P and S doping level, and excellent electrical conductivity. A maximum areal power density of 3134 mW m-2 and current density of 7.56 A m-2 are generated by the MFCs equipped with as-obtained NPS-CF anodes, which is 2.57- and 2.63-fold that of the plain carbon cloth anodes (areal power density of 1218 mW m-2 and current density of 2.87 A m-2), respectively. Such improvement is explored to mainly originate from two respects: the good biocompatibility of NPS-CFs favors the bacterial adhesion and enrichment of electroactive Geobacter species on the electrode surface, while the high conductivity and improved bacteria-electrode interaction efficiently promote the extracellular electron transfer (EET) between the bacteria and the anode. This study provides a low-cost and sustainable way to fabricate high power MFCs for practical applications.

Bacterial Cellulose as a Supersoft Neural Interfacing Substrate.

Biocompatible neural interfaces hold great promise for treating neurological disorders and enhancing the mental and physical ability of human beings. Most of the currently available neural interfaces are made from rigid, dense inorganic materials that cause tissue damage. We present supersoft multichannel electrodes by depositing gold layers on thin bacterial cellulose (BC) (Au-BC electrodes). The Young's modulus of BC ( EBC = 120 kPa) is between those of the brain tissue ( Ebrain = 2.7-3.1 kPa) and the peripheral neural tissues ( Eperipheral nerve = 580-840 kPa). The bending stiffness of the Au-BC electrodes corresponds to 1/5200 of Au-polyimide electrodes with the same layout. Furthermore, the Au-BC electrodes are highly durable (conductivity >95% after 100 cycles of 180° bending). In vivo recording of brain electric activity demonstrates the great potential of the Au-BC electrodes for neural interfacing applications.

Pharmaceutical Intermediate-Modified Gold Nanoparticles: Against Multidrug-Resistant Bacteria and Wound-Healing Application via an Electrospun Scaffold.

Remedying a multidrug-resistant (MDR) bacteria wound infection is a major challenge due to the inability of conventional antibiotics to treat such infections against MDR bacteria. Thus, developing wound dressings for wound care, particularly against MDR bacteria, is in huge demand. Here, we present a strategy in designing wound dressings: we use a small molecule (6-aminopenicillanic acid, APA)-coated gold nanoparticles (AuNPs) to inhibit MDR bacteria. We dope the AuNPs into electrospun fibers of poly(ε-caprolactone) (PCL)/gelatin to yield materials that guard against wound infection by MDR bacteria. We systematically evaluate the bactericidal activity of the AuNPs and wound-healing capability via the electrospun scaffold. APA-modified AuNPs (Au_APA) exhibit remarkable antibacterial activity even when confronted with MDR bacteria. Meanwhile, Au_APA has outstanding biocompatibility. Moreover, an in vivo bacteria-infected wound-healing experiment indicates that it has a striking ability to remedy a MDR bacteria wound infection. This wound scaffold can assist the wound care for bacterial infections.

Small Molecular TGF-ß1-Inhibitor-Loaded Electrospun Fibrous Scaffolds for Preventing Hypertrophic Scars.

Hypertrophic scarring (HS) is a disorder that occurs during wound healing and seriously depresses the quality of human life. Scar-inhibiting scaffolds, though bringing promise to HS prevention, face problems such as the incompatibility of the scaffold materials and the instability of bioactive molecules. Herein, we present a TGF-ß1-inhibitor-doped poly(ε-caprolactone) (PCL)/gelatin (PG) coelectrospun nanofibrous scaffold (PGT) for HS prevention during wound healing. The appropriate ratio of PCL to gelatin can avoid individual defects of the two materials and achieve an optimized mechanical property and biocompatibility. The TGF-ß1 inhibitor (SB-525334) is a small molecule and is highly stable during electrospinning and drug release processes. The PGT effectively inhibits fibroblast (the major cell type contributing to scar formation) proliferation in vitro and successfully prevents HS formation during the healing of full-thickness model wounds on rabbit ear. Our strategy offers an excellent solution for potential large-scale production of scaffolds for clinical HS prevention.

Skiving stacked sheets of paper into test paper for rapid and multiplexed assay.

This paper shows that stacked sheets of paper preincubated with different biological reagents and skiving them into uniform test paper sheets allow mass manufacturing of multiplexed immunoassay devices and simultaneous detection of multiplex targets that can be read out by a barcode scanner. The thickness of one sheet of paper can form the width of a module for the barcode; when stacked, these sheets of paper can form a series of barcodes representing the targets, depending on the color contrast provided by a colored precipitate of an immunoassay. The uniform thickness of sheets of paper allows high-quality signal readout. The manufacturing method allows highly efficient fabrication of the materials and substrates for a straightforward assay of targets that range from drugs of abuse to biomarkers of blood-transmitted infections. In addition, as a novel alternative to the conventional point-of-care testing method, the paper-based barcode assay system can provide highly efficient, accurate, and objective diagnoses.

Biomimetic nanofibers can construct effective tissue-engineered intervertebral discs for therapeutic implantation.

We present a total tissue engineered (TE) intervertebral disc (IVD) to address IVD degradation, which is a major cause of chronic neck and back pain. The TE IVD is comprised of an alginate hydrogel-based nucleus pulposus (NP) and hierarchically organized, concentric ring-aligned electrospun (ES) polycaprolactone (PCL)/poly (d,l-lactide-co-glycolide) (PLGA)/Collagen type I (PPC)-based annulus fibrosus (AF). The TE IVD exhibits excellent hydrophilicity to simulate highly hydrated native IVD. Long-term in vivo implantation assays demonstrate the excellent structural (shape maintenance, hydration, and integration with surrounding tissues) and functional (mechanical supporting and flexibility) performances of the TE IVD. Our study provides a novel approach for treating IVD degeneration.

Construction of Small-Diameter Vascular Graft by Shape-Memory and Self-Rolling Bacterial Cellulose Membrane.

Bacterial cellulose (BC) membranes with shape-memory properties allow the rapid preparation of artificial small-diameter blood vessels when combined with microfluidics-based patterning with multiple types of cells. Lyophilization of a wet multilayered rolled BC tube endows it with memory to recover its tubular shape after unrolling. The unrolling of the BC tube yields a flat membrane, and subsequent patterning with endothelial cells, smooth muscle cells, and fibroblast cells is carried out by microfluidics. The cell-laden BC membrane is then rerolled into a multilayered tube. The different cells constituting multiple layers on the tubular wall can imitate blood vessels in vitro. The BC tubes (2 mm) without cell modification, when implanted into the carotid artery of a rabbit, maintain thrombus-free patency 21 d after implantation. This study provides a novel strategy for the rapid construction of multilayered small-diameter BC tubes which may be further developed for potential applications as artificial blood vessels.