A critical review of fabrication challenges and reliability issues in top/bottom gated MoS2field-effect transistors.

The voyage of semiconductor industry to decrease the size of transistors to achieve superior device performance seems to near its physical dimensional limitations. The quest is on to explore emerging material systems that offer dimensional scaling to match the silicon- based technologies. The discovery of atomic flat two-dimensional materials has opened up a completely new avenue to fabricate transistors at sub-10 nanometer level which has the potential to compete with modern silicon-based semiconductor devices. Molybdenum disulfide (MoS2) is a two-dimensional layered material with novel semiconducting properties at atomic level seems like a promising candidate that can possibly meet the expectation of Moore's law. This review discusses the various 'fabrication challenges' in making MoS2based electronic devices from start to finish. The review outlines the intricate challenges of substrate selection and various synthesis methods of mono layer and few-layer MoS2. The review focuses on the various techniques and methods to minimize interface defect density at substrate/MoS2interface for optimum MoS2-based device performance. The tunable band-gap of MoS2with varying thickness presents a unique opportunity for contact engineering to mitigate the contact resistance issue using different elemental metals. In this work, we present a comprehensive overview of different types of contact materials with myriad geometries that show a profound impact on device performance. The choice of different insulating/dielectric gate oxides on MoS2in co-planar and vertical geometry is critically reviewed and the physical feasibility of the same is discussed. The experimental constraints of different encapsulation techniques on MoS2and its effect on structural and electronic properties are extensively discussed.

Bioengineered 3D microfibrous-matrix modulates osteopontin release from MSCs and facilitates the expansion of hematopoietic stem cells.

The osteopontin (OPN) released from mesenchymal stem cells (MSCs) undergoing lineage differentiation can negatively influence the expansion of hematopoietic stem cells (HSCs) in coculture systems developed for expanding HSCs. Therefore, minimizing the amount of OPN in the coculture system is important for the successful ex vivo expansion of HSCs. Toward this goal, a bioengineered three dimensional (3D) microfibrous-matrix that can maintain MSCs in less OPN-releasing conditions has been developed, and its influence on the expansion of HSCs has been studied. The newly developed 3D matrix significantly decreased the release of OPN, depending on the MSC culture conditions used during the priming period before HSC seeding. The culture system with the lowest amount of OPN facilitated a more than 24-fold increase in HSC number in 1 week time period. Interestingly, the viability of expanded cells and the CD34+   pure population of HSCs were found to be the highest in the low OPN-containing system. Therefore, bioengineered microfibrous 3D matrices seeded with MSCs, primed under suitable culture conditions, can be an improved ex vivo expansion system for HSC culture.

A novel small diameter nanotextile arterial graft is associated with surgical feasibility and safety and increased transmural endothelial ingrowth in pig.

Globally, millions of patients are affected by myocardial infarction or lower limb gangrene/amputation due to atherosclerosis. Available surgical treatment based on vein and synthetic grafts provides sub-optimal benefits. We engineered a highly flexible and mechanically robust nanotextile-based vascular graft (NanoGraft) by interweaving nanofibrous threads of poly-L-lactic acid to address the unmet need. The NanoGrafts were rendered impervious with selective fibrin deposition in the micropores by pre-clotting. The pre-clotted NanoGrafts (4 mm diameter) and ePTFE were implanted in a porcine carotid artery replacement model. The fibrin-laden porous milieu facilitated rapid endothelization by the transmural angiogenesis in the NanoGraft. In-vivo patency of NanoGrafts was 100% at 2- and 4-weeks, with no changes over time in lumen size, flow velocities, and minimal foreign-body inflammatory reaction. However, the patency of ePTFE at 2-week was 66% and showed marked infiltration, neointimal thickening, and poor host tissue integration. The study demonstrates the in-vivo feasibility and safety of a thin-layered vascular prosthesis, viz., NanoGraft, and its potential superiority over the commercial ePTFE.

Exploiting the preferential phagocytic uptake of nanoparticle-antigen conjugates for the effective treatment of autoimmunity.

Tolerance induction is central to the suppression of autoimmunity. Here, we engineered the preferential uptake of nano-conjugated autoantigens by spleen-resident macrophages to re-introduce self-tolerance and suppress autoimmunity. The brain autoantigen, myelin oligodendrocyte glycoprotein (MOG), was conjugated to 200 or 500 nm silica nanoparticles (SNP) and delivered to the spleen and liver-resident macrophages of experimental autoimmune encephalomyelitis (EAE) mice, used as a model of multiple sclerosis. MOG-SNP conjugates significantly reduced signs of EAE at a very low dose (50 µg) compared to the higher dose (>800 µg) of free-MOG. This was associated with reduced proliferation of splenocytes and pro-inflammatory cytokines secretion, decreased spinal cord inflammation, demyelination and axonal damage. Notably, biodegradable porous SNP showed an enhanced disease suppression assisted by elevated levels of regulatory T cells and programmed-death ligands (PD-L1/2) in splenic and lymph node cells. Our results demonstrate that targeting nano-conjugated autoantigens to tissue-resident macrophages in lymphoid organs can effectively suppress autoimmunity.

Correction to: Evaluation of Wound Healing Potential of ß-Chitin Hydrogel/Nano Zinc Oxide Composite Bandage.

In the original manuscript, the platelet activation images of the sample treated groups, Fig. 3c were provided incorrectly.

Magnetic 3D scaffold: A theranostic tool for tissue regeneration and non-invasive imaging in vivo.

We report an osteoconducting magnetic 3D scaffold using Fe2+ doped nano-hydroxyapatite-Alginate-Gelatin (AGHFe1) for Magnetic Resonance Imaging based non-invasive monitoring of bone tissue regeneration. In rat cranial defect model, the scaffold facilitated non-invasive monitoring of cell migration, inflammatory response and matrix deposition by unique changes in transverse relaxation time (T2). Cell infiltration resulted in a considerable increase in T2 from ~37 to ~62 ms, which gradually returned to that of native bone (~23 ms) by 90 days. We used this method to compare in vivo performance of scaffold with bone-morphogenic protein-2 (AGHFe2) or faster degrading (AGHFe3). MRI and histological analysis over 90 days showed non-uniform bone formation in AGHFe1 with ∆T2 (T2Native bone - T2 Regenerated bone) ~13 ms, whereas, AGHFe2 and AGHFe3 showed ∆T2 ~ 09 and 05 ms respectively, suggesting better bone formation in AGHFe3. Thus, we show that MR-contrast enabled scaffold can help better assessment of bone-regeneration non-invasively.

Long-term drug delivery using implantable electrospun woven polymeric nanotextiles.

A woven nanotextile implant was developed and optimized for long-term continuous drug delivery for potential oncological applications. Electrospun polydioxanone (PDS) nanoyarns, which are twisted bundles of PDS nanofibres, were loaded with paclitaxel (PTX) and woven into nanotextiles of different packing densities. A mechanistic modeling of in vitro drug release proved that a combination of diffusion and matrix degradation controlled the slow PTX-release from a nanoyarn, emphasizing the role of nanostructure in modulating release kinetics. Woven nanotextiles, through variations in its packing density and thereby architecture, demonstrated tuneable PTX-release. In vivo PTX-release, pharmacokinetics and biodistribution were evaluated in healthy BALB/c mice by suturing the nanotextile to peritoneal wall. The slow and metronomic PTX-release for 60 days from the loosely woven implant was extremely effective in enhancing its residence in peritoneum, in contrast to intraperitoneal injections. Such an implantable matrix offers a novel platform for therapy of solid tumors over prolonged durations.

Interface-engineered Li4Ti5O12-TiO2 dual-phase nanoparticles and CNT additive for supercapacitor-like high-power Li-ion battery applications.

The single-pot synthesis of dual-phase spinel-Li4Ti5O12 and anatase-TiO2 (LTO-TiO2) nanoparticles over all the phase fractions ranging from pure LTO to pure TiO2 is conducted. Carrying out the process over the complete range enabled the identification of a unique weight ratio of 85:15 (LTO:TiO2), providing the best combination of capacity, rate capability and cycling stability. We show that for this composition dual-phase nanoparticles have a predominant interfacial orientation of (111)LTO∣∣(004)TiO2 , while it is (111)LTO∣∣(101)TiO2 for other compositions. This study therefore shows that the dual-phase interface with these specific orientations gives the best performance. The synergistic combination of dual-phase nanoparticles with multi-wall carbon nanotubes improves the performance further. This results in an electrode with supercapacitor-like rate capability delivering high discharge capacities of 174, 127, 119, 110, 101 and 91 mAh g-1 at specific currents of 2000, 6000, 12 000, 18 000, 24 000 and 30 000 mA g-1, respectively. A discharge capacity of 174 mAh g-1 at a specific current of 2000 mA g-1 with only 0.005% capacity loss per cycle over 3000 cycles is demonstrated. At current densities of 6000, 12 000 and 24 000 mA g-1, stable cycling is obtained for 1500 cycles. The present work enables nano-engineered interfaces in LTO-TiO2 dual-phase nanoparticles with an electrochemical performance that is better than its individual components, opening up the potential for high-power Li-ion battery applications.

On the physics of dispersive electron transport characteristics in SnO2 nanoparticle-based dye sensitized solar cells.

The present study elucidates dispersive electron transport mediated by surface states in tin oxide (SnO2) nanoparticle-based dye sensitized solar cells (DSSCs). Transmission electron microscopic studies on SnO2 show a distribution of ∼10 nm particles exhibiting (111) crystal planes with inter-planar spacing of 0.28 nm. The dispersive transport, experienced by photo-generated charge carriers in the bulk of SnO2, is observed to be imposed by trapping and de-trapping processes via SnO2 surface states present close to the band edge. The DSSC exhibits 50% difference in performance observed between the forward (4%) and reverse (6%) scans due to the dispersive transport characteristics of the charge carriers in the bulk of the SnO2. The photo-generated charge carriers are captured and released by the SnO2 surface states that are close to the conduction band-edge resulting in a very significant variation; this is confirmed by the hysteresis observed in the forward and reverse scan current-voltage measurements under AM1.5 illumination. The hysteresis behavior assures that the charge carriers are accumulated in the bulk of electron acceptor due to the trapping, and released by de-trapping mediated by surface states observed during the forward and reverse scan measurements.

Integrating Substrateless Electrospinning with Textile Technology for Creating Biodegradable Three-Dimensional Structures.

The present study describes a unique way of integrating substrateless electrospinning process with textile technology. We developed a new collector design that provided a pressure-driven, localized cotton-wool structure in free space from which continuous high strength yarns were drawn. An advantage of this integration was that the textile could be drug/dye loaded and be developed into a core-sheath architecture with greater functionality. This method could produce potential nanotextiles for various biomedical applications.

Graphene oxide nanoflakes incorporated gelatin-hydroxyapatite scaffolds enhance osteogenic differentiation of human mesenchymal stem cells.

In this study, graphene oxide (GO) nanoflakes (0.5 and 1 wt%) were incorporated into a gelatin-hydroxyapatite (GHA) matrix through a freeze drying technique and its effect to enhance mechanical strength and osteogenic differentiation was studied. The GHA matrix with GO demonstrated less brittleness in comparison to GHA scaffolds. There was no significant difference in mechanical strength between GOGHA0.5 and GOGHA1.0 scaffolds. When the scaffolds were immersed in phosphate buffered saline (to mimic physiologic condition) for 60 days, around 50-60% of GO was released in sustained and linear manner and the concentration was within the toxicity limit as reported earlier. Further, GOGHA0.5 scaffolds were continued for cell culture experiments, wherein the scaffold induced osteogenic differentiation of human adipose derived mesenchymal stem cells without providing supplements like dexamethasone, L-ascorbic acid and ß glycerophosphate in the medium. The level of osteogenic differentiation of stem cells was comparable to those cultured on GHA scaffolds with osteogenic supplements. Thus biocompatible, biodegradable and porous GO reinforced gelatin-HA 3D scaffolds may serve as a suitable candidate in promoting bone regeneration in orthopaedics.

Mn-doped zinc sulphide nanocrystals for immunofluorescent labeling of epidermal growth factor receptors on cells and clinical tumor tissues.

The field of molecular detection and targeted imaging has evolved considerably with the introduction of fluorescent semiconductor nanocrystals. Manganese-doped zinc sulphide nanocrystals (ZnS:Mn NCs), which are widely used in electroluminescent displays, have been explored for the first time for direct immunofluorescent (IF) labeling of clinical tumor tissues. ZnS:Mn NCs developed through a facile wet chemistry route were capped using amino acid cysteine, conjugated to streptavidin and thereafter coupled to biotinylated epidermal growth factor receptor (EGFR) antibody utilizing the streptavidin-biotin linkage. The overall conjugation yielded stable EGFR antibody conjugated ZnS:Mn NCs (EGFR ZnS:Mn NCs) with a hydrodynamic diameter of 65 ± 15 nm, and having an intense orange-red fluorescence emission at 598 nm. Specific labeling of EGF receptors on EGFR(+ve) A431 cells in a co-culture with EGFR(-ve) NIH3T3 cells was demonstrated using these nanoprobes. The primary antibody conjugated fluorescent NCs could also clearly delineate EGFR over-expressing cells on clinical tumor tissues processed by formalin fixation as well as cryopreservation with a specificity of 86% and accuracy of 88%, in comparison to immunohistochemistry. Tumor tissues labeled with EGFR ZnS:Mn NCs showed good fluorescence emission when imaged after storage even at 15 months. Thus, ZnS nanobioconjugates with dopant-dependent and stable fluorescence emission show promise as an efficient, target-specific fluorophore that would enable long term IF labeling of any antigen of interest on clinical tissues.

On global energy scenario, dye-sensitized solar cells and the promise of nanotechnology.

One of the major problems that humanity has to face in the next 50 years is the energy crisis. The rising population, rapidly changing life styles of people, heavy industrialization and changing landscape of cities have increased energy demands, enormously. The present annual worldwide electricity consumption is 12 TW and is expected to become 24 TW by 2050, leaving a challenging deficit of 12 TW. The present energy scenario of using fossil fuels to meet the energy demand is unable to meet the increase in demand effectively, as these fossil fuel resources are non-renewable and limited. Also, they cause significant environmental hazards, like global warming and the associated climatic issues. Hence, there is an urgent necessity to adopt renewable sources of energy, which are eco-friendly and not extinguishable. Of the various renewable sources available, such as wind, tidal, geothermal, biomass, solar, etc., solar serves as the most dependable option. Solar energy is freely and abundantly available. Once installed, the maintenance cost is very low. It is eco-friendly, safely fitting into our society without any disturbance. Producing electricity from the Sun requires the installation of solar panels, which incurs a huge initial cost and requires large areas of lands for installation. This is where nanotechnology comes into the picture and serves the purpose of increasing the efficiency to higher levels, thus bringing down the overall cost for energy production. Also, emerging low-cost solar cell technologies, e.g. thin film technologies and dye-sensitized solar cells (DSCs) help to replace the use of silicon, which is expensive. Again, nanotechnological implications can be applied in these solar cells, to achieve higher efficiencies. This paper vividly deals with the various available solar cells, choosing DSCs as the most appropriate ones. The nanotechnological implications which help to improve their performance are dealt with, in detail. Additionally, the economic and ecological aspects of using nanotechnology are briefly introduced.

The role of nanotechnology in prostate cancer theranostic applications.

Recent advancements in cancer nanotechnology have facilitated a better way to diagnosis and provide therapy for prostate cancer. Nanotechnology has the potential to battle tumors at the site, where the cancer begins. There is a need to improve the therapeutic availabilities and the effectiveness of conventional chemotherapeutic agents for prostate cancer. Many therapeutic NPs have been developed with nanotechnology that can specifically target and deliver variety of agents including chemo drugs to destruct the prostate cancer cells without causing any damage to the healthy cells. Theranostic NPs have been developed to specifically target the prostate cancer cells using targeting ligands and to release the anticancer agents in a controlled and time-dependent manner for cancer therapy in combination with assisted imaging to monitor the effectiveness of the therapy in real time. The natural products and surface-modified polymers and metallic NPs have evolved as promising nanomaterials for targeted prostate cancer treatment. This review focuses on the role of alternative medicine, polymeric and metallic and metal oxide NPs in prostate cancer theranostics.

Nano-graphene oxide particles induce inheritable anomalies through altered gene expressions involved in oocyte maturation.

The inheritable impact of exposure to graphene oxide nanoparticles (GO NPs) on vertebrate germline during critical windows of gamete development remain undetermined to date. Here, we analyzed the transgenerational effects of exposure to nano-graphene oxide particles (nGO) synthesized in house with lateral dimensions 300-600 nm and surface charge of -36.8 mV on different developmental stages of germ cells (GCs): (1) during GCs undergoing early development and differentiation, and (2) during GCs undergoing gametogenesis and maturation in adulthood. Biocompatibility analyses in Japanese medaka embryos showed lethality above 1 µg/ml and also an aberrant increase in germ cell count of both males and females at doses below the lethal dose. However, no lethality or anomalies were evident in adults up to 45 µg/ml. Long term exposure of embryos and adults for 21 days resulted in reduced fecundity. This effect was transmitted to subsequent generations, F1 and F2. Importantly, the inheritable effects of nGO in adults were pronounced at a high dose of 10 µg/ml, while 1 µg/ml showed no impact on the germline indicating lower doses used in this study to be safe. Further, expressions of selected genes that adversely affected oocyte maturation were enhanced in F1 and F2 individuals. Interestingly, the inheritance patterns differed corresponding to the stage at which the fish received the exposure.

Evaluation of wound healing potential of ß-chitin hydrogel/nano zinc oxide composite bandage.

PURPOSE: ß-chitin hydrogel/nZnO composite bandage was fabricated and evaluated in detail as an alternative to existing bandages. METHODS: ß-chitin hydrogel was synthesized by dissolving ß-chitin powder in Methanol/CaCl(2) solvent, followed by the addition of distilled water. ZnO nanoparticles were added to the ß-chitin hydrogel and stirred for homogenized distribution. The resultant slurry was frozen at 0°C for 12 h. The frozen samples were lyophilized for 24 h to obtain porous composite bandages. RESULTS: The bandages showed controlled swelling and degradation. The composite bandages showed blood clotting ability as well as platelet activation, which was higher when compared to the control. The antibacterial activity of the bandages were proven against Staphylococcus aureus (S. aureus) and Escherichia coli (E.coli). Cytocompatibility of the composite bandages were assessed using human dermal fibroblast cells (HDF) and these cells on the composite bandages were viable similar to the Kaltostat control bandages and bare ß-chitin hydrogel based bandages. The viability was reduced to 50-60% in bandages with higher concentration of zinc oxide nanoparticles (nZnO) and showed 80-90% viability with lower concentration of nZnO. In vivo evaluation in Sprague Dawley rats (S.D. rats) showed faster healing and higher collagen deposition ability of composite bandages when compared to the control. CONCLUSIONS: The prepared bandages can be used on various types of infected wounds with large volume of exudates.

Smart Design for Hybrid Bioprinting of Scalable and Viable Tissue Constructs.

Hybrid bioprinting uses sequential printing of melt-extruded biodegradable thermoplastic polymer and cell-encapsulated bioink in a predesigned manner using high- and low-temperature print heads for the fabrication of robust three-dimensional (3D) biological constructs. However, the high-temperature print head and melt-extruded polymer cause irreversible thermal damage to the bioprinted cells, and it affects viability and functionality of 3D bioprinted biological constructs. Thus, there is an urgent need to develop innovative approaches to protect the bioprinted cells, coming into contact or at close proximities to the melt-extruded thermoplastic polymer and the high-temperature print head during hybrid bioprinting. Therefore, this study investigated the potential of iterating the structural architecture pattern (SAP) of melt-printed thermoplastic layers and the cell printing pattern (CPP) to protect the cells from temperature-associated damage during hybrid bioprinting. A novel SAP for printing the thermoplastic polymer and an associated CPP for minimizing thermal damage to the 3D bioprinted construct have been developed. The newly developed SAP- and CPP-based hybrid bioprinted biological constructs showed significantly low thermal damage compared to conventionally hybrid bioprinted biological constructs. The results from this study suggest that the newly developed SAP and CPP can be an improved hybrid bioprinting strategy for developing living constructs at the human scale.

Development and characterisation of suitably bioengineered microfibrillar matrix-based 3D prostate cancer model forin vitrodrug testing.

Bioengineered 3D models that can mimic patient-specific pathologiesin vitroare valuable tools for developing and validating anticancer therapeutics. In this study, microfibrillar matrices with unique structural and functional properties were fabricated as 3D spherical and disc-shaped scaffolds with highly interconnected pores and the potential of the newly developed scaffolds for developing prostate cancer model has been investigated. The newly developed scaffolds showed improved cell retention upon seeding with cancer cells compared to conventional electrospun scaffolds. They facilitated rapid growth and deposition of cancer-specific extracellular matrix through-the-thickness of the scaffold. Compared to the prostate cancer cells grown in 2D culture, the newly developed prostate cancer model showed increased resistance to the chemodrug Docetaxel regardless of the drug concentration or the treatment frequency. A significant reduction in the cell number was observed within one week after the drug treatment in the 2D culture for both PC3 and patient-derived cells. Interestingly, almost 20%-30% of the cancer cells in the newly developed 3D model survived the drug treatment, and the patient-derived cells were more resistant than the tested cell line PC3. The results from this study indicate the potential of the newly developed prostate cancer model forin vitrodrug testing.

Intracranial nanomedicine-gel with deep brain-penetration for glioblastoma therapy.

Glioblastoma Multiforme (GBM) is one of the challenging tumors to treat as it recurs, almost 100%, even after surgery, radiation, and chemotherapy. In many cases, recurrence happens within 2-3cm depth of the resected tumor margin, indicating the inefficacy of current anti-glioma drugs to penetrate deep into the brain tissue. Here, we report an injectable nanoparticle-gel system, capable of providing deep brain penetration of drug up to 4 cm, releasing in a sustained manner up to >15 days. The system consists of ∼222 nm sized PLGA nanoparticles (NP-222) loaded with an anti-glioma drug, Carmustine (BCNU), and coated with a thick layer of polyethylene glycol (PEG). Upon release of the drug from PLGA core, it will interact with the outer PEG-layer leading to the formation of PEG-BCNU nanocomplexes of size ∼33 nm (BCNU-NC-33), which could penetrate >4 cm deep into the brain tissue compared to the free drug (< 5 mm). In vitro drug release showed sustained release of drug for 15 days by BCNU-NP gel, and enhanced cytotoxicity by BCNU-NC-33 drug-nanocomplexes in glioma cell lines. Ex vivo goat-brain phantom studies showed drug diffusion up to 4 cm in tissue and in vivo brain-diffusion studies showed almost complete coverage within the rat brain (∼1.2 cm), with ∼55% drug retained in the tissue by day-15, compared to only ∼5% for free BCNU. Rat orthotopic glioma studies showed excellent anti-tumor efficacy by BCNU-NP gel compared to free drug, indicating the potential of the gel-system for anti-glioma therapy. In effect, we demonstrate a unique method of sustained release of drug in the brain using larger PLGA nanoparticles acting as a reservoir while deep-penetration of the released drug was achieved by in situ formation of drug-nanocomplexes of size <50 nm which is less than the native pore size of brain tissue (> 100 nm). This method will have a major impact on a challenging field of brain drug delivery.