Development of a model of barriers to environmentally conscious manufacturing implementation

Manufacturing firms consume energy and natural resources in highly unsustainable manner and release large amounts of green house gases leading to many economic, environmental and social problems from climate change to local waste disposal. Consciousness about these issues has led to a new manufacturing paradigm of environmentally conscious manufacturing (ECM). However, there are various barriers to the implementation of ECM. A proper understanding and analysis of these barriers will allow the management of the company and government to prioritise their focus to mitigate root barriers for effective implementation of ECM. This paper aims at identifying the barriers to ECM, developing a model of these barriers using statistical analysis and testing the model using structural equation modelling technique. The results provide three types of barriers – internal, policy and economic. The results show that internal barriers are the root barriers and cause policy and economic barriers. It reflects that the barriers which are internal to the organisation should be mitigated first for effective implementation of ECM.     

Nanohydroxyapatite shape and its potential role in bone formation: an analytical study

Bone cells (osteoblasts) produce a collagen-rich matrix called osteoid, which is mineralized extracellularly by nanosized calcium phosphate (CaP). Synthetically produced CaP nanoparticles (NPs) have great potential for clinical application. However few studies have compared the effect of CaP NPs with different properties, such as shape and aspect ratio, on the survival and behaviour of active bone-producing cells, such as primary human osteoblasts (HOBs). This study aimed to investigate the biocompatibility and ultrastructural effects of two differently shaped hydroxyapatite [Ca₁₀(PO₄)₆(OH)₂] nanoparticles (HA NPs), round- (aspect ratio 2.12, AR2) and rice-shaped (aspect ratio 3.79, AR4). The ultrastructural response and initial extracellular matrix (ECM) formation of HOBs to HA NPs were observed, as well as matrix vesicle release. A transmission electron microscopy (TEM)-based X-ray microanalytical technique was used to measure cytoplasmic ion levels, including calcium (Ca), phosphorus (P), sodium (Na) and potassium (K). K/Na ratios were used as a measure of cell viability. Following HA NP stimulation, all measured cytoplasmic ion levels increased. AR2 NPs had a greater osteogenic effect on osteoblasts compared with AR4 NPs, including alkaline phosphatase activity and matrix vesicle release. However, they produced only a moderate increase in intracellular Ca and P levels compared with AR4. This suggests that particular Ca and P concentrations may be required for, or indicative of, optimal osteoblast activity. Cell viability, as measured by Na and K microanalysis, was best maintained in AR2. Initial formation of osteoblast ECM was altered in the presence of either HA NP, and immuno-TEM identified fibronectin and matrilin-3 as two ECM proteins affected. Matrilin-3 is here described for the first time as being expressed by cultured osteoblasts. In summary, this novel and in-depth study has demonstrated that HA NP shape can influence a range of different parameters related to osteoblast viability and activity.     

Toxicological hazards of inhaled nanoparticles--potential implications for drug delivery

Nanoparticles (NP), here defined as particles with a diameter smaller then 100 nm, are increasingly used in different applications, including drug carrier systems and to pass organ barriers such as the blood-brain barrier. On the other hand, a large body of know-how is available regarding toxicological effects of nanoparticle (NP) after inhalation. More specifically, a number of effects of inhaled NP are attributed to their (i) direct effects on the central nervous system, (ii) their translocation from the lung into the bloodstream, and (iii) their capacity to invoke inflammatory responses in the lung with subsequent systemic effects. This paper gives a brief review on the toxicology of inhaled NP, including general principles and current paradigms to explain the special case of NP in pulmonary toxicology. Since the evidence for health risks of NP after inhalation has been increasing over the last decade, this paper tries to extrapolate these findings and principles observed in inhalation toxicology into recommendations and methods for testing NP for nanocarrier purposes. A large gap is present between research on NP in inhalation toxicology and in nanoscaled drug carrying. This review recommends a closer interaction between both disciplines to gain insight in the role of NP size and properties and their mechanisms of acute and chronic interaction with biological systems.     

甲基三乙氧基硅烷改性溶胶制备陶瓷化木材的性能

采用甲基三乙氧基硅烷(MTES)与正硅酸乙酯(TEOS)共水解获得改性溶胶,然后将溶胶通过真空-加压设备浸注入木材内部,并发生凝胶复合制备陶瓷化木材,解决了TEOS水解溶胶制备的陶瓷化木材脆性大、耐水性差的问题。改性凝胶具有疏水性,降低了陶瓷化木材的吸水增重率,提高了抗压和抗弯曲强度等力学性能。     

Construction of collagen II/hyaluronate/chondroitin-6-sulfate tri-copolymer scaffold for nucleus pulposus tissue engineering and preliminary analysis of its physico-chemical properties and biocompatibility

To construct a novel scaffold for nucleus pulposus (NP) tissue engineering, The porous type II collagen (CII)/hyaluronate (HyA)–chondroitin-6-sulfate (6-CS) scaffold was prepared using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) and N-hydroxysuccinimide (NHS) cross-linking system. The physico-chemical properties and biocompatibility of CII/HyA–CS scaffolds were evaluated. The results suggested CII/HyA–CS scaffolds have a highly porous structure (porosity: 94.8 ± 1.5%), high water-binding capacity (79.2 ± 2.8%) and significantly improved mechanical stability by EDC/NHS crosslinking (denaturation temperature: 74.6 ± 1.8 and 58.1 ± 2.6°C, respectively, for the crosslinked scaffolds and the non-crosslinked; collagenase degradation rate: 39.5 ± 3.4 and 63.5 ± 2.0%, respectively, for the crosslinked scaffolds and the non-crosslinked). The CII/HyA–CS scaffolds also showed satisfactory cytocompatibility and histocompatibility as well as low immunogenicity. These results indicate CII/HyA–CS scaffolds may be an alternative material for NP tissue engineering due to the similarity of its composition and physico-chemical properties to those of the extracellular matrices (ECM) of native NP.     

Development of acetazolamide-loaded,pH-triggered polymeric nanoparticulate in situ gel for sustained ocular delivery: in vitro. ex vivo evaluation and pharmacodynamic study

The objective of research was to develop a novel pH-triggered polymeric nanoparticulate in situ gel (NP-ISG) for ophthalmic delivery of acetazolamide (ACZ) to enhance the conjunctival permeation and precorneal residence time of the formulation by overcoming the limitations of protective ocular barriers. Nanoparticles (NP1--NP12) were developed by nanoprecipitation method and evaluated for pharmacotechnical characteristics including transmission electron microscopy. The optimized formulation, NP10 was dispersed in carbopol 934?P to form nanoparticulate in situ gels (NP-ISG1--NP-ISG5). NP-ISG5 was selected as optimized formulation on the basis of gelation ability and residence time. Ex vivo transcorneal permeation study exhibited significantly higher ACZ permeation from NP-ISG5 (74.50?±?2.20?mg/cm²) and NP10 (93.5?±?2.25?mg/cm²) than eye drops (20.08?±?3.12?mg/cm²) and ACZ suspension (16.03?±?2.14). Modified Draize test with zero score indicated nonirritant property of NP-ISG5. Corneal toxicity study revealed no visual signs of tissue damage. Further, NP-ISG5 when tested for hypotensive effect on intraocular pressure (IOP) in rabbits revealed that NP-ISG5 caused significant decrease in IOP (p?in vitro efficacy, safety and patient compliance.     

Status of engineering change management in the engineer-to-order production environment: insights from a multiple case study

Engineering Changes (ECs) are a fact of life for companies in the Engineer-To-Order (ETO) production environment. Various Engineering Change Management (ECM) strategies, practices and tools exist, but no explicit distinction has been made regarding ECM in different production environments. Using a multiple case study method, this article investigates how ETO companies manage ECs and how ETO characteristics influence ECM. A generic ECM framework was developed and used to map ECM in the cases. The study showed that ETO companies use similar practices for handling ECs, while ECM tools are either not used by the companies or used to a very limited extent. It was found that the use of some ECM practices and tools is complicated by specific ETO company characteristics. However, no reasons were found for the lack of computer-based tools, change propagation and impact assessment tools, change reduction and front-loading tools, and design tools. This suggests, firstly, that there is vast room for improvement in ETO companies when it comes to ECM; and secondly, that the applicability of such tools should be further tested in the ETO environment. Based on the findings, some suggestions as to how ECM can be improved in ETO companies are given to practitioners.     

Water-Induced Separation of Polymers from High Nanoparticle-Content Nanocomposite Films

Polymer nanocomposites with high loadings of nanoparticles (NPs) exhibit exceptional mechanical and transport properties. Separation of polymers and NPs from such nanocomposites is a critical step in enabling the recycling of these components and reducing the potential environmental hazards that can be caused by the accumulation of nanocomposite wastes in landfills. However, the separation typically requires the use of organic solvents or energy-intensive processes. Using polydimethylsiloxane (PDMS)-infiltrated SiO₂ NP films, we demonstrate that the polymers can be separated from the SiO₂ NP packings when these nanocomposites are exposed to high humidity and water. The findings indicate that the charge state of the NPs plays a significant role in the propensity of water to undergo capillary condensation within the PDMS-filled interstitial pores. We also show that the size of NPs has a crucial impact on the kinetics and extent of PDMS expulsion, illustrating the importance of capillary forces in inducing PDMS expulsion. We demonstrate that the separated polymer can be collected and reused to produce a new nanocomposite film. The work provides insightful guidelines on how to design and fabricate end-of-life recyclable high-performance nanocomposites.     

Defect properties in a VTaCrW equiatomic high entropy alloy(HEA)with the body centered cubic(bcc) structure

We report first-principles results of the point defect properties in a V-Ta-Cr-W high-entropy alloy(HEA)with the body-centered cubic(bcc) structure. Different from the widely-investigated face-centered cubic(fcc) HEAs, the local lattice distortion is more pronounced in bcc ones, which has a strong influence on the defect properties and defect evolution under irradiation. Due to the large size of Ta, the exchange between vacancies and Ta exhibits lower energy barriers. On the other hand, interstitial dumbbells containing V and Cr possess lower formation energies. These defect energetics predicts an enrichment of V and Cr and a depletion of Ta and W in the vicinity of defect sinks. Besides, we find that interstitial dumbbells favor the [110] orientation in the HEA, instead of [111] direction in most nonmagnetic bcc metals,which helps to slow down interstitial diffusion significantly. Consequently, the distribution of migration energies for vacancies and interstitials exhibit much larger overlap regions in the bcc HEA compared to fcc HEAs, leading to the good irradiation resistance by enhancing defect recombination. Our results suggest that HEAs with the bcc structure may bear excellent irradiation tolerance due to the particular defect properties.     

Size-controlled one-pot synthesis of fluorescent cadmium sulfide semiconductor nanoparticles in an apoferritin cavity

A simple size-controlled synthesis of cadmium sulfide (CdS) nanoparticle (NP) cores in the cavity of apoferritin from horse spleen (HsAFr) was performed by a slow chemical reaction synthesis and a two-step synthesis protocol. We found that the CdS NP core synthesis was slow and that premature CdS NP cores were formed in the apoferritin cavity when the concentration of ammonia water was low. It was proven that the control of the ammonia water concentration can govern the CdS NP core synthesis and successfully produce size-controlled CdS NP cores with diameters from 4.7 to 7.1?nm with narrow size dispersion. X-ray powder diffraction (XRD), energy dispersive spectroscopy (EDS) analysis and high-resolution transmission electron microscopy (HR-TEM) observation characterized the CdS NP cores obtained as cubic polycrystalline NPs, which showed photoluminescence with red shifts depending on their diameters. From the research of CdS NP core synthesis in the recombinant apoferritins, the zeta potential of apoferritin is important for the biomineralization of CdS NP cores in the apoferritin cavity. These synthesized CdS NPs with different photoluminescence properties will be applicable in a wide variety of nano-applications.     

Interstitial Occupancy by Extrinsic Alkali Cations in Perovskites and Its Impact on Ion Migration

Recent success in achieving highly stable Rb‐containing organolead halide perovskites has indicated the possibility of incorporating small monovalent cations, which cannot fit in the lead‐halide cage with an appropriate tolerance factor, into the perovskite lattice while maintaining a pure stable “black” phase. In this study, through a combined experimental and theoretical investigation by density functional theory (DFT) calculations on the incorporation of extrinsic alkali cations (Rb⁺, K⁺, Na⁺, and Li⁺) in perovskite materials, the size‐dependent interstitial occupancy of these cations in the perovskite lattice is unambiguously revealed. Interestingly, DFT calculations predict the increased ion migration barriers in the lattice after the interstitial occupancy. To verify this prediction, ion migration behavior is characterized through hysteresis analysis of solar cells, electrical poling, temperature‐dependent conductivity, and time‐dependent photoluminescence measurements. The results collectively point to the suppression of ion migration after lattice interstitial occupancy by extrinsic alkali cations. The findings of this study provide new material design principles to manipulate the structural and ionic properties of multication perovskite materials.     

Label-free Raman monitoring of extracellular matrix formation in three-dimensional polymeric scaffolds

Monitoring extracellular matrix (ECM) components is one of the key methods used to determine tissue quality in three-dimensional scaffolds for regenerative medicine and clinical purposes. Raman spectroscopy can be used for non-invasive sensing of cellular and ECM biochemistry. We have investigated the use of conventional (confocal and semiconfocal) Raman microspectroscopy and fibre-optic Raman spectroscopy for in vitro monitoring of ECM formation in three-dimensional poly(ethylene oxide terephthalate)–poly(butylene terephthalate) (PEOT/PBT) scaffolds. Chondrocyte-seeded PEOT/PBT scaffolds were analysed for ECM formation by Raman microspectroscopy, biochemical analysis, histology and scanning electron microscopy. ECM deposition in these scaffolds was successfully detected by biochemical and histological analysis and by label-free non-destructive Raman microspectroscopy. In the spectra collected by the conventional Raman set-ups, the Raman bands at 937 and at 1062 cm⁻¹ which, respectively, correspond to collagen and sulfated glycosaminoglycans could be used as Raman markers for ECM formation in scaffolds. Collagen synthesis was found to be different in single chondrocyte-seeded scaffolds when compared with microaggregate-seeded samples. Normalized band-area ratios for collagen content of single cell-seeded samples gradually decreased during a 21-day culture period, whereas collagen content of the microaggregate-seeded samples significantly increased during this period. Moreover, a fibre-optic Raman set-up allowed for the collection of Raman spectra from multiple pores inside scaffolds in parallel. These fibre-optic measurements could give a representative average of the ECM Raman signal present in tissue-engineered constructs. Results in this study provide proof-of-principle that Raman microspectroscopy is a promising non-invasive tool to monitor ECM production and remodelling in three-dimensional porous cartilage tissue-engineered constructs.     

Nanospheres of a bisphosphonate attenuate intimal hyperplasia

The present study explored a novel strategy for attenuation of restenosis after arterial injury by a bisphosphonate encapsulated in polymeric nanoparticles (NP) for transient selective depletion of macrophages. A bisphosphonate (BP), 2-(2-Aminopyrimidino) ethyldiene-1,1-bisphosphonic acid betaine (ISA), was successfully formulated in 400 nm sized polylactide/glycolide-based NP with high yield (69%) and entrapment efficiency (60% w/w). ISA NP, but not blank NP or free ISA, exhibited specific and significant cytotoxic effect on macrophages-like RAW 264 cells, in a dose-dependent manner, with no inhibitory effect on the growth of smooth muscle cells (SMCs). Fluorescent pyrene-labeled NP were shown to be taken up by RAW 264 cells, but not by SMCs. Intravenously (i.v.) administered ISA NP (15 mg/kg, single dose on day-1) resulted in a significant attenuation of neointima to media area ratio (N/M) by 40% and stenosis by 45% 14 days after rat carotid injury, in comparison to animals treated with free ISA, buffer or blank NP. However, the effect was not preserved 30 days post injury, and an insignificant reduction of neointimal formation was observed. Neointimal hyperplasia was also significantly suppressed after subcutaneous (SC) injection of ISA NP (15 mg/kg, single dose on day-1), reducing both N/M and stenosis. Intraperitoneal (i.p.) injection of silica, a known selective toxin for macrophages, (1000 mg/kg), also resulted in a significant inhibition of N/M and stenosis, which further reinforces the cause-effect relationship of macrophage-inactivation and the prevention of neointima formation. Biocompatible and biodegradable NP loaded with ISA characterized by high colloidal stability, reproducible activity, and high drug entrapment warrant further consideration for restenosis therapy, and may be useful in other disease processes involving monocytes/macrophages.     

Examining MRI contrast in three-dimensional cell culture phantoms with DNA-templated nanoparticle chains

DNA-templated nanoparticle (NP) chains were examined as potential magnetic resonance imaging (MRI) contrast agents using in vitro environments of the extracellular matrix and tissue. A 3-T clinical MRI scanner was utilized to examine and compare image contrast enhanced by dispersed NPs, DNA-templated NP chains, gold-superparamagnetic multicomponent NP chains, and polyelectrolyte encapsulated, multicomponent NP chains in both T(1)-weighted and T(2)-weighted images. In addition, the longitudinal and transverse relaxivity (r(1) and r(2)) changes were measured both in the basement membrane, using Matrigel, and in the tissue environment, using in vitro 3D cell culture scaffolds. Results suggest that MRI contrast was significantly enhanced from NP chains compared to dispersed NPs in the basement membrane and polyelectrolyte encapsulation for NP chains produced similar relaxivity to nonencapsulated NP chains due to the enhanced cell uptake of encapsulated NP chains.     

Characteristics of environmental factor for electrochemical migration on printed circuit board

This study investigates whether electrochemical migration (ECM) is affected by factors such as the printed circuit board (PCB) material, distance between the conductors, bias voltage, contamination and underfill process under water drop (WD), temperature and humidity bias (THB), and polarization tests. The resistance of ECM with polyimide PCB was greater than that with FR-4 (flame resistant-4) PCB. The ECM rate was increased by decreasing the distance between the conductors of opposite polarity and increasing the bias voltage. The cured underfill on PCB protected the ECM growth, while contamination with chlorine ions accelerated the ECM growth.     

Energetics of Ti atom diffusion into diamond film

Energetics of Ti atom in metallization of diamond film were studied by calculations using density functional theory (DFT) and a composite basis set. Cluster models consisting of more than 10 C atoms were chosen to simulate the diamond phase with their boundaries saturated with H atoms. When Ti atom diffuses from the surface into the bulk of diamond interstitially, the energy barriers were found to be about 40 eV. Ti was found to favor substitutional sites rather than interstitial sites in diamond crystal. Our results indicate that the high concentration of Ti in chemical vapor deposited diamond films after metallization would occupy the grain boundaries rather than the bulk of diamond grain.     

Migration of intervertebral disc cells into dense collagen scaffolds intended for functional replacement

Invasion of cells from surrounding tissues is a crucial step for regeneration when using a-cellular scaffolds as a replacement of the nucleus pulposus (NP). The aim of current study was to assess whether NP and surrounding annulus fibrosus (AF) cells are capable of migrating into dense collagen scaffolds. We seeded freshly harvested caprine NP and AF cells onto scaffolds consisting of 1.5 and 3.0% type I collagen matrices, prepared by plastic compression, to assess cell invasion. The migration distance appeared both time and density dependent and was higher for NP (25%) compared to AF (10%) cells after 4 weeks. Migration distance was not enhanced by Hst-2, a peptide derived from saliva known to enhance fibroblast migration, and this was confirmed in a scratch assay. In conclusion, we revealed invasion of cells into dense collagen scaffolds and therewith encouraging first steps towards the use of a-cellular scaffolds for NP replacement.     

Low molecular weight heparin-loaded polymeric nanoparticles: formulation,characterization, and release characteristics

The aim of the present work was to investigate the preparation of low molecular weight heparin (LMWH) nanoparticles (NP) as potential oral heparin carriers. The NP were formulated using an ultrasound probe by water-in-oil-in-water (w/o/w) emulsification and solvent evaporation with two biodegradable polymers [poly-epsilon-caprolactone, PCL and poly(D,L-lactic-co-glycolic acid) 50/50, PLGA] and two non-biodegradable positively charged polymers (Eudragit RS and RL) used alone or in combination. The mean diameter of LMWH-loaded NP ranged from 240 to 490 nm and was dependent on the reduced viscosity of the polymeric organic solution. The surface potential of LMWH NP prepared with Eudragit polymers used alone or blended with PCL and PLGA was changed dramatically from strong positive values obtained with unloaded NP to negative values. The highest encapsulation efficiencies were observed when Eudragit polymers took part in the composition of the polymeric matrix, compared with PCL and PLGA NP exhibiting low LMWH entrapment. The in vitro LMWH release in phosphate buffer from all formulations ranged from 10 to 25% and was more important (two- to threefold) when esterase was added into the dissolution medium. The in vitro biological activity of released LMWH, determined by the anti-factor Xa activity with a chromogenic substrate, was preserved after the encapsulation process, making these NP good candidates for oral administration.     

Human vascular endothelial cells in primary cell culture for the evaluation of nanoparticle bioadhesion

Nanoparticles (NP) are employed in various therapeutic approaches for innovative drug delivery strategies. Among them, there is drug delivery to the brain and sustained release forms for intravenous drug delivery. In order to optimize drug carriers and to elucidate involved mechanisms such as bioadhesion and cellular uptake, NP were surface modified and analyzed for their interaction with human endothelial cells in cell culture. Fluorescently labeled NP of different diameters (50 to 1000 nm) were surface modified either by simple adsorption of chitosan or by covalent binding to the lectin ulex europaeus agglutinin and thereafter applied to human endothelial cells for different incubation periods. After incubation with NP the binding of NP was quantified directly by the fluorescence emission signals from the cell layers. In order to visualize the binding behaviour, NP were localized three-dimensionally in the cell layer by confocal laser scanning microscopy. Cell binding experiments in phosphate buffer were observed to be particle size dependent with the 50 nm NP showing the highest binding percentage over all experiments. Binding decreased with increasing particle diameter and shorter incubation interval. The adhesion was further enhanced by NP surface modifications in the order blank < chitosan < lectin. The presence of plasma proteins enhanced the adhesiveness of chitosan coated NP, while the binding of lectin coated NP was inhibited. Experiments at 4 degrees C indicated the involvement of an active process in the binding of NP to endothelial cells.     

Investigations on pharmacokinetics and biodistribution of polymeric and solid lipid nanoparticulate systems of atypical antipsychotic drug: effect of material used and surface modification

The present study focuses on the effect of material used for the preparation of nanoparticulate (NP) systems and surface modification on the pharmacokinetics and biodistribution of atypical antipsychotic, olanzapine (OLN). NP carriers of OLN were prepared from two different materials such as polymer (polycaprolactone) and solid lipid (Glyceryl monostearate). These systems were further surface modified with surfactant, Polysorbate 80 and studied for pharmacokinetics–biodistribution in Wistar rats using in-house developed bioanalytical methods. The pharmacokinetics and biodistribution studies resulted in a modified and varied distribution of NP systems with higher area under curve (AUC) values along with prolonged residence time of OLN in the rat blood circulation. The distribution of OLN to the brain was significantly enhanced with surfactant surface-modified NP systems, followed by nonsurface-modified NP formulations as compared with pure OLN solution. Biodistribution study demonstrated a low uptake of obtained NP systems by kidney and heart, thereby decreasing the nephrotoxicity and adverse cardiovascular effects. By coating the NP with surfactant, uptake of macrophage was found to be reduced. Thus, our studies confirmed that the biodistribution OLN could be modified effectively by incorporating in NP drug delivery systems prepared from different materials and surface modifications. A judicious selection of materials used for the preparation of delivery carriers and surface modifications would help to design a most efficient drug delivery system with better therapeutic efficacy.