Search results for: nano composites

Authors: M. Naveed Yasin, Robert Brooke, Andrew Chan, Geoffrey I. N. Waterhouse, Drew Evans, Darren Svirskis, Ilva D. Rupenthal

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Poly(3,4-ethylenedioxythiophene) (PEDOT) is a robust conducting polymer (CP) exhibiting high conductivity and environmental stability. It can be synthesized by either chemical, electrochemical or vapour phase polymerization (VPP). Dexamethasone sodium phosphate (dexP) is an anionic drug molecule which has previously been loaded onto PEDOT as a dopant via electrochemical polymerisation; however this technique requires conductive surfaces from which polymerization is initiated. On the other hand, VPP produces highly organized biocompatible CP structures while polymerization can be achieved onto a range of surfaces with a relatively straight forward scale-up process. Following VPP of PEDOT, dexP can be loaded and subsequently released via ion-exchange. This study aimed at preparing and characterising both non-porous and porous VPP PEDOT structures including examining drug loading and release via ion-exchange. Porous PEDOT structures were prepared by first depositing a sacrificial polystyrene (PS) colloidal template on a substrate, heat curing this deposition and then spin coating it with the oxidant solution (iron tosylate) at 1500 rpm for 20 sec. VPP of both porous and non-porous PEDOT was achieved by exposing to monomer vapours in a vacuum oven at 40 mbar and 40 °C for 3 hrs. Non-porous structures were prepared similarly on the same substrate but without any sacrificial template. Surface morphology, compositions and behaviour were then characterized by atomic force microscopy (AFM), scanning electron microscopy (SEM), x-ray photoelectron spectroscopy (XPS) and cyclic voltammetry (CV) respectively. Drug loading was achieved by 50 CV cycles in a 0.1 M dexP aqueous solution. For drug release, each sample was exposed to 20 mL of phosphate buffer saline (PBS) placed in a water bath operating at 37 °C and 100 rpm. Film was stimulated (continuous pulse of ± 1 V at 0.5 Hz for 17 mins) while immersed into PBS. Samples were collected at 1, 2, 6, 23, 24, 26 and 27 hrs and were analysed for dexP by high performance liquid chromatography (HPLC Agilent 1200 series). AFM and SEM revealed the honey comb nature of prepared porous structures. XPS data showed the elemental composition of the dexP loaded film surface, which related well with that of PEDOT and also showed that one dexP molecule was present per almost three EDOT monomer units. The reproducible electroactive nature was shown by several cycles of reduction and oxidation via CV. Drug release revealed success in drug loading via ion-exchange, with stimulated porous and non-porous structures exhibiting a proof of concept burst release upon application of an electrical stimulus. A similar drug release pattern was observed for porous and non-porous structures without any significant statistical difference, possibly due to the thin nature of these structures. To our knowledge, this is the first report to explore the potential of VPP prepared PEDOT for stimuli-responsive drug delivery via ion-exchange. The produced porous structures were ordered and highly porous as indicated by AFM and SEM. These porous structures exhibited good electroactivity as shown by CV. Future work will investigate porous structures as nano-reservoirs to increase drug loading while sealing these structures to minimize spontaneous drug leakage.

Keywords: PEDOT for ion-exchange drug delivery, stimuli-responsive drug delivery, template based porous PEDOT structures, vapour phase polymerization of PEDOT

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Authors: Ece A. Irmak, Amdulla O. Mekhrabov, M. Vedat Akdeniz

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There is a growing interest on the synthesis and characterization of nanoalloys since the unique chemical, and physical properties of nanoalloys can be tuned and, consequently, new structural motifs can be created by varying the type of constituent elements, atomic and magnetic ordering, as well as size and shape of the nanoparticles. Due to the fine size effects, magnetic nanoalloys have considerable attention with their enhanced mechanical, electrical, optical and magnetic behavior. As an important magnetic nanoalloy, the novel application area of Fe-Ni based nanoalloys is expected to be widened in the chemical, aerospace industry and magnetic biomedical applications. Noble metals have been using in biomedical applications for several years because of their surface plasmon properties. In this respect, iron-nickel nanoalloys are promising materials for magnetic biomedical applications because they show novel properties such as superparamagnetism and surface plasmon resonance property. Also, there is great attention for the usage Fe-Ni based nanoalloys as radar absorbing materials in aerospace and stealth industry due to having high Curie temperature, high permeability and high saturation magnetization with good thermal stability. In this study, FeNi₃ bimetallic nanoalloys were synthesized by mechanical alloying in a planetary high energy ball mill. In mechanical alloying, micron size powders are placed into the mill with milling media. The powders are repeatedly deformed, fractured and alloyed by high energy collision under the impact of balls until the desired composition and particle size is achieved. The experimental studies were carried out in two parts. Firstly, dry mechanical alloying with high energy dry planetary ball milling was applied to obtain FeNi₃ nanoparticles. Secondly, dry milling was followed by surfactant-assisted ball milling to observe the surfactant and solvent effect on the structure, size, and properties of the FeNi₃ nanoalloys. In the first part, the powder sample of iron-nickel was prepared according to the 1:3 iron to nickel ratio to produce FeNi₃ nanoparticles and the 1:10 powder to ball weight ratio. To avoid oxidation during milling, the vials had been filled with Ar inert gas before milling started. The powders were milled for 80 hours in total and the synthesis of the FeNi₃ intermetallic nanoparticles was succeeded by mechanical alloying in 40 hours. Also, regarding the particle size, it was found that the amount of nano-sized particles raised with increasing milling time. In the second part of the study, dry milling of the Fe and Ni powders with the same stoichiometric ratio was repeated. Then, to prevent agglomeration and to obtain smaller sized nanoparticles with superparamagnetic behavior, surfactants and solvent are added to the system, after 40-hour milling time, with the completion of the mechanical alloying. During surfactant-assisted ball milling, heptane was used as milling medium, and as surfactants, oleic acid and oleylamine were used in the high energy ball milling processes. The characterization of the alloyed particles in terms of microstructure, morphology, particle size, thermal and magnetic properties with respect to milling time was done by X-ray diffraction, scanning electron microscopy, energy dispersive spectroscopy, vibrating-sample magnetometer, and differential scanning calorimetry.

Keywords: iron-nickel systems, magnetic nanoalloys, mechanical alloying, nanoalloy characterization, surfactant-assisted ball milling

Procedia PDF Downloads 149

Authors: Zhao Gao, Eran Edirisinghe

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The production of an accurate sketch of a suspect based on a verbal description obtained from a witness is an essential task for most criminal investigations. The criminal investigation system employs specifically trained professional artists to manually draw a facial image of the suspect according to the descriptions of an eyewitness for subsequent identification. Within the advancement of Deep Learning, Recurrent Neural Networks (RNN) have shown great promise in Natural Language Processing (NLP) tasks. Additionally, Generative Adversarial Networks (GAN) have also proven to be very effective in image generation. In this study, a trained GAN conditioned on textual features such as keywords automatically encoded from a verbal description of a human face using an RNN is used to generate photo-realistic facial images for criminal investigations. The intention of the proposed system is to map corresponding features into text generated from verbal descriptions. With this, it becomes possible to generate many reasonably accurate alternatives to which the witness can use to hopefully identify a suspect from. This reduces subjectivity in decision making both by the eyewitness and the artist while giving an opportunity for the witness to evaluate and reconsider decisions. Furthermore, the proposed approach benefits law enforcement agencies by reducing the time taken to physically draw each potential sketch, thus increasing response times and mitigating potentially malicious human intervention. With publically available 'CelebFaces Attributes Dataset' (CelebA) and additionally providing verbal description as training data, the proposed architecture is able to effectively produce facial structures from given text. Word Embeddings are learnt by applying the RNN architecture in order to perform semantic parsing, the output of which is fed into the GAN for synthesizing photo-realistic images. Rather than the grid search method, a metaheuristic search based on genetic algorithms is applied to evolve the network with the intent of achieving optimal hyperparameters in a fraction the time of a typical brute force approach. With the exception of the ‘CelebA’ training database, further novel test cases are supplied to the network for evaluation. Witness reports detailing criminals from Interpol or other law enforcement agencies are sampled on the network. Using the descriptions provided, samples are generated and compared with the ground truth images of a criminal in order to calculate the similarities. Two factors are used for performance evaluation: The Structural Similarity Index (SSIM) and the Peak Signal-to-Noise Ratio (PSNR). A high percentile output from this performance matrix should attribute to demonstrating the accuracy, in hope of proving that the proposed approach can be an effective tool for law enforcement agencies. The proposed approach to criminal facial image generation has potential to increase the ratio of criminal cases that can be ultimately resolved using eyewitness information gathering.

Keywords: RNN, GAN, NLP, facial composition, criminal investigation

Procedia PDF Downloads 135

Authors: Mingxin Li, Liya Ni

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Autonomous parking is a valuable feature applicable to many robotics applications such as tour guide robots, UV sanitizing robots, food delivery robots, and warehouse robots. With auto-parking, the robot will be able to park at the charging zone and charge itself without human intervention. As compared to self-driving vehicles, auto-parking is more challenging for a small-scale mobile robot only equipped with a front camera due to the camera view limited by the robot’s height and the narrow Field of View (FOV) of the inexpensive camera. In this research, auto-parking of a small-scale mobile robot with a front camera only was achieved in a four-step process: Firstly, transfer learning was performed on the AlexNet, a popular pre-trained convolutional neural network (CNN). It was trained with 150 pictures of empty parking slots and 150 pictures of occupied parking slots from the view angle of a small-scale robot. The dataset of images was divided into a group of 70% images for training and the remaining 30% images for validation. An average success rate of 95% was achieved. Secondly, the image of detected empty parking space was processed with edge detection followed by the computation of parametric representations of the boundary lines using the Hough Transform algorithm. Thirdly, the positions of the entrance point and center of available parking space were predicted based on the robot kinematic model as the robot was driving closer to the parking space because the boundary lines disappeared partially or completely from its camera view due to the height and FOV limitations. The robot used its wheel speeds to compute the positions of the parking space with respect to its changing local frame as it moved along, based on its kinematic model. Lastly, the predicted entrance point of the parking space was used as the reference for the motion control of the robot until it was replaced by the actual center when it became visible again by the robot. The linear and angular velocities of the robot chassis center were computed based on the error between the current chassis center and the reference point. Then the left and right wheel speeds were obtained using inverse kinematics and sent to the motor driver. The above-mentioned four subtasks were all successfully accomplished, with the transformed learning, image processing, and target prediction performed in MATLAB, while the motion control and image capture conducted on a self-built small scale differential drive mobile robot. The small-scale robot employs a Raspberry Pi board, a Pi camera, an L298N dual H-bridge motor driver, a USB power module, a power bank, four wheels, and a chassis. Future research includes three areas: the integration of all four subsystems into one hardware/software platform with the upgrade to an Nvidia Jetson Nano board that provides superior performance for deep learning and image processing; more testing and validation on the identification of available parking space and its boundary lines; improvement of performance after the hardware/software integration is completed.

Keywords: autonomous parking, convolutional neural network, image processing, kinematics-based prediction, transfer learning

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Authors: Abdelmessih Malak Sadek Labib

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Ceramic materials are known for their stability in harsh environments and excellent electrical, mechanical, and thermal properties. They have been widely used in various applications despite the emergence of new materials such as plastics and composites. However, ceramics are often brittle, which can lead to catastrophic failure. The fragility of ceramics and the mechanisms behind their failure have been a topic of extensive research, particularly in load-bearing applications like veneers. Porcelain, a type of traditional pottery, is commonly used in such applications. Traditional pottery consists of clay, silica, and feldspar, and the presence of quartz in the ceramic body can lead to microcracks and stress concentrations. The mullite hypothesis suggests that the strength of porcelain can be improved by increasing the interlocking of mullite needles in the ceramic body. However, there is a lack of reports on Young's moduli in the literature, leading to erroneous conclusions about the mechanical behavior of porcelain. This project aims to investigate the role of quartz and mullite on the mechanical strength of various porcelains while considering factors such as particle size, flexural strength, and fractographic forces. Research Aim: The aim of this research project is to assess the role of quartz and mullite in enhancing the mechanical strength of different porcelains. The project will also explore the effect of reducing particle size on the properties of porcelain, as well as investigate flexural strength and fractographic techniques. Methodology: The methodology for this project involves using scientific expressions and a mix of modern English to ensure the understanding of all attendees. It will include the measurement of Young's modulus and the evaluation of the mechanical behavior of porcelains through various experimental techniques. Findings: The findings of this study will provide a realistic assessment of the role of quartz and mullite in strengthening and reducing the fragility of porcelain. The research will also contribute to a better understanding of the mechanical behavior of ceramics, specifically in load-bearing applications. Theoretical Importance: The theoretical importance of this research lies in its contribution to the understanding of the factors influencing the mechanical strength and fragility of ceramics, particularly porcelain. By investigating the interplay between quartz, mullite, and other variables, this study will enhance our knowledge of the properties and behavior of traditional ceramics. Data Collection and Analysis Procedures: Data for this research will be collected through experiments involving the measurement of Young's modulus and other mechanical properties of porcelains. The effects of quartz, mullite, particle size, flexural strength, and fractographic forces will be examined and analyzed using appropriate statistical techniques and fractographic analysis. Questions Addressed: This research project aims to address the following questions: (1) How does the presence of quartz and mullite affect the mechanical strength of porcelain? (2) What is the impact of reducing particle size on the properties of porcelain? (3) How do flexural strength and fractographic forces influence the behavior of porcelains? Conclusion: In conclusion, this research project aims to enhance the understanding of the role of quartz and mullite in strengthening and reducing the fragility of porcelain. By investigating the mechanical properties of porcelains and considering factors such as particle size, flexural strength, and fractographic forces, this study will contribute to the knowledge of traditional ceramics and their potential applications. The findings will have practical implications for the use of ceramics in various fields.

Keywords: stability, harsh environments, electrical, techniques, mechanical disadvantages, materials

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Authors: Alex J. Summers, Jasmine P. Devadhasan, Douglas Montgomery, Brittany Fischer, Jian Gu, Frederic Zenhausern

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Immunoassays have been utilized for several applications, including the detection of pathogens. Our laboratory is in the development of a tier 1 biothreat panel utilizing Vertical Flow Assay (VFA) technology for simultaneous detection of pathogens and toxins. One method of manufacturing VFA membranes is with non-contact piezoelectric dispensing, which provides advantages, such as low-volume and rapid dispensing without compromising the structural integrity of antibody or substrate. Challenges of this processinclude premature discontinuation of dispensing and misaligned spotting. Preliminary data revealed the Yp 11C7 mAb (11C7)reagent to exhibit a large angle of failure during printing which may have contributed to variable printing outputs. A Design of Experiment (DOE) was executed using this reagent to investigate the effects of hydrostatic pressure and reagent concentration on microarray printing outputs. A Nano-plotter 2.1 (GeSIM, Germany) was used for printing antibody reagents ontonitrocellulose membrane sheets in a clean room environment. A spotting plan was executed using Spot-Front-End software to dispense volumes of 11C7 reagent (20-50 droplets; 1.5-5 mg/mL) in a 6-test spot array at 50 target membrane locations. Hydrostatic pressure was controlled by raising the Pressure Compensation Vessel (PCV) above or lowering it below our current working level. It was hypothesized that raising or lowering the PCV 6 inches would be sufficient to cause either liquid accumulation at the tip or discontinue droplet formation. After aspirating 11C7 reagent, we tested this hypothesis under stroboscope.75% of the effective raised PCV height and of our hypothesized lowered PCV height were used. Humidity (55%) was maintained using an Airwin BO-CT1 humidifier. The number and quality of membranes was assessed after staining printed membranes with dye. The droplet angle of failure was recorded before and after printing to determine a “stroboscope score” for each run. The DOE set was analyzed using JMP software. Hydrostatic pressure and reagent concentration had a significant effect on the number of membranes output. As hydrostatic pressure was increased by raising the PCV 3.75 inches or decreased by lowering the PCV -4.5 inches, membrane output decreased. However, with the hydrostatic pressure closest to equilibrium, our current working level, membrane output, reached the 50-membrane target. As the reagent concentration increased from 1.5 to 5 mg/mL, the membrane output also increased. Reagent concentration likely effected the number of membrane output due to the associated dispensing volume needed to saturate the membranes. However, only hydrostatic pressure had a significant effect on stroboscope score, which could be due to discontinuation of dispensing, and thus the stroboscope check could not find a droplet to record. Our JMP predictive model had a high degree of agreement with our observed results. The JMP model predicted that dispensing the highest concentration of 11C7 at our current PCV working level would yield the highest number of quality membranes, which correlated with our results. Acknowledgements: This work was supported by the Chemical Biological Technologies Directorate (Contract # HDTRA1-16-C-0026) and the Advanced Technology International (Contract # MCDC-18-04-09-002) from the Department of Defense Chemical and Biological Defense program through the Defense Threat Reduction Agency (DTRA).

Keywords: immunoassay, microarray, design of experiment, piezoelectric dispensing

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Authors: Alper T. Celebi, Ali Beskok

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Electroosmotic (EO) slip flows in nanochannels are investigated using non-equilibrium molecular dynamics (MD) simulations, and the results are compared with analytical solution of Poisson-Boltzmann and Stokes (PB-S) equations with slip contribution. The ultimate objective of this study is to show that well-known continuum flow model can accurately predict the EO velocity profiles in nanochannels using the slip lengths and apparent viscosities obtained from force-driven flow simulations performed at various liquid-wall interaction strengths. EO flow of aqueous NaCl solution in silicon nanochannels are simulated under realistic electrochemical conditions within the validity region of Poisson-Boltzmann theory. A physical surface charge density is determined for nanochannels based on dissociations of silanol functional groups on channel surfaces at known salt concentration, temperature and local pH. First, we present results of density profiles and ion distributions by equilibrium MD simulations, ensuring that the desired thermodynamic state and ionic conditions are satisfied. Next, force-driven nanochannel flow simulations are performed to predict the apparent viscosity of ionic solution between charged surfaces and slip lengths. Parabolic velocity profiles obtained from force-driven flow simulations are fitted to a second-order polynomial equation, where viscosity and slip lengths are quantified by comparing the coefficients of the fitted equation with continuum flow model. Presence of charged surface increases the viscosity of ionic solution while the velocity-slip at wall decreases. Afterwards, EO flow simulations are carried out under uniform electric field for different liquid-wall interaction strengths. Velocity profiles present finite slips near walls, followed with a conventional viscous flow profile in the electrical double layer that reaches a bulk flow region in the center of the channel. The EO flow enhances with increased slip at the walls, which depends on wall-liquid interaction strength and the surface charge. MD velocity profiles are compared with the predictions from analytical solutions of the slip modified PB-S equation, where the slip length and apparent viscosity values are obtained from force-driven flow simulations in charged silicon nano-channels. Our MD results show good agreements with the analytical solutions at various slip conditions, verifying the validity of PB-S equation in nanochannels as small as 3.5 nm. In addition, the continuum model normalizes slip length with the Debye length instead of the channel height, which implies that enhancement in EO flows is independent of the channel height. Further MD simulations performed at different channel heights also shows that the flow enhancement due to slip is independent of the channel height. This is important because slip enhanced EO flow is observable even in micro-channels experiments by using a hydrophobic channel with large slip and high conductivity solutions with small Debye length. The present study provides an advanced understanding of EO flows in nanochannels. Correct characterization of nanoscale EO slip flow is crucial to discover the extent of well-known continuum models, which is required for various applications spanning from ion separation to drug delivery and bio-fluidic analysis.

Keywords: electroosmotic flow, molecular dynamics, slip length, velocity-slip

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Authors: Banu Pradheepa Kamarajan, Muthusamy Ananthasubramanian

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Biofilm forming Pseudomonads occupy the top third position in causing hospital acquired infections. P. aeruginosa is notoriously known for its tendency to develop drug resistance. Major classes of drug such as β-lactams, aminoglycosides, quinolones, and polymyxins are found ineffective against multi-drug resistance Pseudomonas. To combat the infections, rather than administration of a single antibiotic, use of combinations (tobramycin and essential oils from plants and/or silver nanoparticles, chitosan, nitric oxide, cis-2-decenoic acid) in single formulation are suggested to control P. aeruginosa biofilms. Conventional techniques to prevent hospital-acquired implant infections such as coatings with antibiotics, controlled release of antibiotics from the implant material, contact-killing surfaces, coating the implants with functional DNase I and, coating with glycoside hydrolase are being followed. Coatings with bioactive components besides having limited shelf-life, require cold-chain and, are likely to fail when bacteria develop resistance. Recently identified nano-scale physical architectures on the insect wings are expected to have potential bactericidal property. Nanopillars are bactericidal to Staphylococcus aureus, Bacillus subtilis, K. pnuemoniae and few species of Pseudomonas. Our study aims to investigate the survival rate of biofilm forming Pseudomonas aeruginosa strain over non-biofilm forming strain on the nanopillar architecture of dragonfly (Pantala flavescens) wing. Dragonflies were collected near house-hold areas and, insect identification was carried out by the Department of Entomology, Tamilnadu Agricultural University, Coimbatore, India. Two strains of P. aeruginosa such as PAO1 (potent biofilm former) and MTCC 1688 (non-weak biofilm former) were tested against the glass coverslip (control) and wings of dragonfly (test) for 48 h. The wings/glass coverslips were incubated with bacterial suspension in 48-well plate. The plates were incubated at 37 °C under static condition. Bacterial attachment on the nanopillar architecture of the wing surface was visualized using FESEM. The survival rate of P. aeruginosa was tested using colony counting technique and flow cytometry at 0.5 h, 1 h, 2 h, 7 h, 24 h, and 48 h post-incubation. Cell death was analyzed using propidium iodide staining and DNA quantification. The results indicated that the survival rate of non-biofilm forming P. aeruginosa is 0.2 %, whilst that of biofilm former is 45 % on the dragonfly wings at the end of 48 h. The reduction in the survival rate of biofilm and non-biofilm forming P. aeruginosa was 20% and 40% respectively on the wings compared to the glass coverslip. In addition, Fourier Transformed Infrared Radiation was used to study the modification in the surface chemical composition of the wing during bacterial attachment and, post-sonication. This result indicated that the chemical moieties are not involved in the bactericidal property of nanopillars by the conserved characteristic peaks of chitin pre and post-sonication. The nanopillar architecture of the dragonfly wing efficiently deters the survival of non-biofilm forming P. aeruginosa, but not the biofilm forming strain. The study highlights the ability of biofilm formers to survive on wing architecture. Understanding this survival strategy will help in designing the architecture that combats the colonization of biofilm forming pathogens.

Keywords: biofilm, nanopillars, Pseudomonas aeruginosa, survival rate

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Authors: Satam Alotibi, Osama A. Hussein, Aziz H. Al-Shaibani, Nawaf A. Al-Aqeel, Abdellah Kaiba, Fatehia S. Alhakami, Mohammed Alyami, Talal F. Qahtan

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The demand for sustainable and efficient energy conversion using solar energy has grown rapidly in recent years. In this pursuit, solar-to-chemical conversion has emerged as a promising approach, with oxygen vacancies-rich tungsten trioxide (WO₃) playing a crucial role. This study presents a method for synthesizing oxygen vacancies-rich WO3, resulting in a significant enhancement of its photocatalytic activity, representing a significant step towards sustainable energy solutions. Experimental results underscore the importance of oxygen vacancies in modifying the properties of WO₃. These vacancies introduce additional energy states within the material, leading to a reduction in the bandgap, increased light absorption, and acting as electron traps, thereby reducing emissions. Our focus lies in developing oxygen vacancies-rich WO₃, which demonstrates unparalleled potential for improved photocatalytic applications. The effectiveness of oxygen vacancies-rich WO₃ in solar-to-chemical conversion was showcased through rigorous assessments of its photocatalytic degradation performance. Sunlight irradiation was employed to evaluate the material's effectiveness in degrading organic pollutants in wastewater. The results unequivocally demonstrate the superior photocatalytic performance of oxygen vacancies-rich WO₃ compared to conventional WO₃ nanomaterials, establishing its efficacy in sustainable and efficient energy conversion. Furthermore, the synthesized material is utilized to fabricate films, which are subsequently employed in immobilized WO₃ and oxygen vacancies-rich WO₃ reactors for water purification under natural sunlight irradiation. This application offers a sustainable and efficient solution for water treatment, harnessing solar energy for effective decontamination. In addition to investigating the photocatalytic capabilities, we extensively analyze the structural and chemical properties of the synthesized material. The synthesis process involves in situ thermal reduction of WO₃ nano-powder in a nitrogen environment, meticulously monitored using thermogravimetric analysis (TGA) to ensure precise control over the synthesis of oxygen vacancies-rich WO₃. Comprehensive characterization techniques such as UV-Vis spectroscopy, X-ray photoelectron spectroscopy (XPS), FTIR, Raman spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and selected area electron diffraction (SAED) provide deep insights into the material's optical properties, chemical composition, elemental states, structure, surface properties, and crystalline structure. This study represents a significant advancement in sustainable energy conversion through solar-to-chemical processes and water purification. By harnessing the unique properties of oxygen vacancies-rich WO₃, we not only enhance our understanding of energy conversion mechanisms but also pave the way for the development of highly efficient and environmentally friendly photocatalytic materials. The application of this material in water purification demonstrates its versatility and potential to address critical environmental challenges. These findings bring us closer to a sustainable energy future and cleaner water resources, laying a solid foundation for a more sustainable planet.

Keywords: sustainable energy conversion, solar-to-chemical conversion, oxygen vacancies-rich tungsten trioxide (WO₃), photocatalytic activity enhancement, water purification

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Authors: Cynthia K. Burzell

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Aequor's Founder, a Marine and Medical Microbiologist, discovered novel, non-toxic chemicals in the ocean that uniquely remove biofilm in minutes and prevent its formation for days. These chemicals and over 70 synthesized analogs that Aequor developed can replace thousands of toxic biocides used in consumer and industrial products and, as new drug candidates, kill biofilm-forming bacteria and fungi Superbugs -the antimicrobial-resistant (AMR) pathogens for which there is no cure. Cynthia Burzell, PhD., is a Marine and Medical Microbiologist studying natural mechanisms that inhibit biofilm formation on surfaces in contact with water. In 2002, she discovered a new genus and several new species of marine microbes that produce small molecules that remove biofilm in minutes and prevent its formation for days. The molecules include new antimicrobials that can replace thousands of toxic biocides used in consumer and industrial products and can be developed into new drug candidates to kill the biofilm-forming bacteria and fungi -- including the antimicrobial-resistant (AMR) Superbugs for which there is no cure. Today, Aequor has over 70 chemicals that are divided into categories: (1) Novel natural chemicals. Lonza validated that the primary natural chemical removed biofilm in minutes and stated: "Nothing else known can do this at non-toxic doses." (2) Specialty chemicals. 25 of these structural analogs are already approved under the U.S. Environmental Protection Agency (EPA)'s Toxic Substances Control Act, certified as "green" and available for immediate sale. These have been validated for the following agro-industrial verticals: (a) Surface cleaners: The U.S. Department of Agriculture validated that low concentrations of Aequor's formulations provide deep cleaning of inert, nano and organic surfaces and materials; (b) Water treatments: NASA validated that one dose of Aequor's treatment in the International Space Station's water reuse/recycling system lasted 15 months without replenishment. DOE validated that our treatments lower energy consumption by over 10% in buildings and industrial processes. Future validations include pilot projects with the EPA to test efficacy in hospital plumbing systems. (c) Algae cultivation and yeast fermentation: The U.S. Department of Energy (DOE) validated that Aequor's treatment boosted biomass of renewable feedstocks by 40% in half the time -- increasing the profitability of biofuels and biobased co-products. DOE also validated increased yields and crop protection of algae under cultivation in open ponds. A private oil and gas company validated decontamination of oilfield water. (3) New structural analogs. These kill Gram-negative and Gram-positive bacteria and fungi alone, in combinations with each other, and in combination with low doses of existing, ineffective antibiotics (including Penicillin), "potentiating" them to kill AMR pathogens at doses too low to trigger resistance. Both the U.S. National Institutes for Health (NIH) and Department of Defense (DOD) has executed contracts with Aequor to provide the pre-clinical trials needed for these new drug candidates to enter the regulatory approval pipelines. Aequor seeks partners/licensees to commercialize its specialty chemicals and support to evaluate the optimal methods to scale-up of several new structural analogs via activity-guided fractionation and/or biosynthesis in order to initiate the NIH and DOD pre-clinical trials.

Keywords: biofilm, potentiation, prevention, removal

Procedia PDF Downloads 66

Authors: Judy M. Obliosca, Olivia Vest, Sandra Poulos, Kelsi Smith, Tammy Ferguson, Abigail Powers Lott, Alicia K. Smith, Yang Xu, Christopher K. Tison

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Post-Traumatic Stress Disorder (PTSD) is a mental health problem that people may develop after experiencing traumatic events such as combat, natural disasters, and major emotional challenges. Tragically, the number of military personnel with PTSD correlates directly with the number of veterans who attempt suicide, with the highest rate in the Army. Research has shown epigenetic risks in those who are prone to several psychiatric dysfunctions, particularly PTSD. Once initiated in response to trauma, epigenetic alterations in particular, the DNA methylation in the form of 5-methylcytosine (5mC) alters chromatin structure and represses gene expression. Current methods to detect DNA methylation, such as bisulfite-based genomic sequencing techniques, are laborious and have massive analysis workflow while still having high error rates. A faster and simpler detection method of high sensitivity and precision would be useful in a clinical setting to confirm potential PTSD etiologies, prevent other psychiatric disorders, and improve military health. A nano-enhanced Surface Plasmon Resonance imaging (SPRi)-based assay that simultaneously detects site-specific 5mC base (termed as PTSD base) in methylated genes related to PTSD is being developed. The arrays on a sensing chip were first constructed for parallel detection of PTSD bases using synthetic and genomic DNA (gDNA) samples. For the gDNA sample extracted from the whole blood of a PTSD patient, the sample was first digested using specific restriction enzymes, and fragments were denatured to obtain single-stranded methylated target genes (ssDNA). The resulting mixture of ssDNA was then injected into the assay platform, where targets were captured by specific DNA aptamer probes previously immobilized on the surface of a sensing chip. The PTSD bases in targets were detected by anti-5-methylcytosine antibody (anti-5mC), and the resulting signals were then enhanced by the universal nanoenhancer. Preliminary results showed successful detection of a PTSD base in a gDNA sample. Brighter spot images and higher delta values (control-subtracted reflectivity signal) relative to those of the control were observed. We also implemented the in-house surface activation system for detection and developed SPRi disposable chips. Multiplexed PTSD base detection of target methylated genes in blood DNA from PTSD patients of severity conditions (asymptomatic and severe) was conducted. This diagnostic capability being developed is a platform technology, and upon successful implementation for PTSD, it could be reconfigured for the study of a wide variety of neurological disorders such as traumatic brain injury, Alzheimer’s disease, schizophrenia, and Huntington's disease and can be extended to the analyses of other sample matrices such as urine and saliva.

Keywords: epigenetic assay, DNA methylation, PTSD, whole blood, multiplexing

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Authors: Sundaram Arulmozhiraja, Kanade Shimizu, Yuta Yamamoto, Satoshi Ichikawa, Maenaka Katsumi, Hiroaki Tokiwa

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Drug discovery is shifting from small molecule based drugs targeting local active site to middle molecules (MM) targeting large, flat, and groove-shaped binding sites, for example, protein-protein interface because at least half of all targets assumed to be involved in human disease have been classified as “difficult to drug” with traditional small molecules. Hence, MMs such as peptides, natural products, glycans, nucleic acids with various high potent bioactivities become important targets for drug discovery programs in the recent years as they could be used for ‘undruggable” intracellular targets. Cell membrane permeability is one of the key properties of pharmacodynamically active MM drug compounds and so evaluating this property for the potential MMs is crucial. Computational prediction for cell membrane permeability of molecules is very challenging; however, recent advancement in the molecular dynamics simulations help to solve this issue partially. It is expected that MMs with high membrane permeability will enable drug discovery research to expand its borders towards intracellular targets. Further to understand the chemistry behind the permeability of MMs, it is necessary to investigate their conformational changes during the permeation through membrane and for that their interactions with the membrane field should be studied reliably because these interactions involve various non-bonding interactions such as hydrogen bonding, -stacking, charge-transfer, polarization dispersion, and non-classical weak hydrogen bonding. Therefore, parameters-based classical mechanics calculations are hardly sufficient to investigate these interactions rather, quantum mechanical (QM) calculations are essential. Fragment molecular orbital (FMO) method could be used for such purpose as it performs ab initio QM calculations by dividing the system into fragments. The present work is aimed to study the cell permeability of middle molecules using molecular dynamics simulations and FMO-QM calculations. For this purpose, a natural compound syringolin and its analogues were considered in this study. Molecular simulations were performed using NAMD and Gromacs programs with CHARMM force field. FMO calculations were performed using the PAICS program at the correlated Resolution-of-Identity second-order Moller Plesset (RI-MP2) level with the cc-pVDZ basis set. The simulations clearly show that while syringolin could not permeate the membrane, its selected analogues go through the medium in nano second scale. These correlates well with the existing experimental evidences that these syringolin analogues are membrane-permeable compounds. Further analyses indicate that intramolecular -stacking interactions in the syringolin analogues influenced their permeability positively. These intramolecular interactions reduce the polarity of these analogues so that they could permeate the lipophilic cell membrane. Conclusively, the cell membrane permeability of various middle molecules with potent bioactivities is efficiently studied using molecular dynamics simulations. Insight of this behavior is thoroughly investigated using FMO-QM calculations. Results obtained in the present study indicate that non-bonding intramolecular interactions such as hydrogen-bonding and -stacking along with the conformational flexibility of MMs are essential for amicable membrane permeation. These results are interesting and are nice example for this theoretical calculation approach that could be used to study the permeability of other middle molecules. This work was supported by Japan Agency for Medical Research and Development (AMED) under Grant Number 18ae0101047.

Keywords: fragment molecular orbital theory, membrane permeability, middle molecules, molecular dynamics simulation

Procedia PDF Downloads 144

Authors: Lizeth Fuentes-Mera, Vanessa Perez-Silos, Nidia K. Moncada-Saucedo, Alejandro Garcia-Ruiz, Alberto Camacho, Jorge Lara-Arias, Ivan Marino-Martinez, Victor Romero-Diaz, Adolfo Soto-Dominguez, Humberto Rodriguez-Rocha, Hang Lin, Victor Pena-Martinez

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Biphasic scaffolds in cartilage tissue engineering have been designed to influence not only the recapitulation of the osteochondral architecture but also to take advantage of the healing ability of bone to promote the implant integration with the surrounding tissue and then bone restoration and cartilage regeneration. This study reports the development and characterization of a biphasic scaffold based on the assembly of a cartilage phase constituted by fibroin biofunctionalized with bovine cartilage matrix; cellularized with differentiated pre-chondrocytes from adipose tissue stem cells (autologous) and well attached to a bone phase (bone bovine decellularized) to mimic the structure of the nature of native tissue and to promote the cartilage regeneration in a model of joint damage in pigs. Biphasic scaffolds were assembled by fibroin crystallization with methanol. The histological and ultrastructural architectures were evaluated by optical and scanning electron microscopy respectively. Mechanical tests were conducted to evaluate Young's modulus of the implant. For the biological evaluation, pre-chondrocytes were loaded onto the scaffolds and cellular adhesion, proliferation, and gene expression analysis of cartilage extracellular matrix components was performed. The scaffolds that were cellularized and matured for 10 days were implanted into critical 3 mm in diameter and 9-mm in depth osteochondral defects in a porcine model (n=4). Three treatments were applied per knee: Group 1: monophasic cellular scaffold (MS) (single chondral phase), group 2: biphasic scaffold, cellularized only in the chondral phase (BS1), group 3: BS cellularized in both bone and chondral phases (BS2). Simultaneously, a control without treatment was evaluated. After 4 weeks of surgery, integration and regeneration tissues were analyzed by x-rays, histology and immunohistochemistry evaluation. The mechanical assessment showed that the acellular biphasic composites exhibited Young's modulus of 805.01 kPa similar to native cartilage (400-800 kPa). In vitro biological studies revealed the chondroinductive ability of the biphasic implant, evidenced by an increase in sulfated glycosaminoglycan (GAGs) and type II collagen, both secreted by the chondrocytes cultured on the scaffold during 28 days. No evidence of adverse or inflammatory reactions was observed in the in vivo trial; however, In group 1, the defects were not reconstructed. In group 2 and 3 a good integration of the implant with the surrounding tissue was observed. Defects in group 2 were fulfilled by hyaline cartilage and normal bone. Group 3 defects showed fibrous repair tissue. In conclusion; our findings demonstrated the efficacy of biphasic and bioactive scaffold based on silk fibroin, which entwined chondroinductive features and biomechanical capability with appropriate integration with the surrounding tissue, representing a promising alternative for osteochondral tissue-engineering applications.

Keywords: biphasic scaffold, extracellular cartilage matrix, silk fibroin, osteochondral tissue engineering

Procedia PDF Downloads 123

Authors: Mikaela Kutrolli, Noah S. Pereira, Vanessa Scanlon, Mohamadmahdi Samandari, Ali Tamayol

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Bone tissue engineering has drawn significant attention and various biomaterials have been tested. Polymers such as polycaprolactone (PCL) offer excellent biocompatibility, reasonable mechanical properties, and biodegradability. However, PCL scaffolds suffer a critical drawback: a lack of micro/mesoporosity, affecting cell attachment, tissue integration, and mineralization. It also results in a slow degradation rate. While 3D-printing has addressed the issue of macroporosity through CAD-guided fabrication, PCL scaffolds still exhibit poor smaller-scale porosity. To overcome this, we generated composites of PCL, hydroxyapatite (HA), and powdered sucrose (PS). The latter serves as a sacrificial material to generate porous particles after sucrose dissolution. Additionally, we have incorporated dexamethasone (DEX) to boost the PCL osteogenic properties. The resulting scaffolds maintain controlled macroporosity from the lattice print structure but also develop micro/mesoporosity within PCL fibers when exposed to aqueous environments. The study involved mixing PS into solvent-dissolved PCL in different weight ratios of PS to PCL (70:30, 50:50, and 30:70 wt%). The resulting composite was used for 3D printing of scaffolds at room temperature. Printability was optimized by adjusting pressure, speed, and layer height through filament collapse and fusion test. Enzymatic degradation, porogen leaching, and DEX release profiles were characterized. Physical properties were assessed using wettability, SEM, and micro-CT to quantify the porosity (percentage, pore size, and interconnectivity). Raman spectroscopy was used to verify the absence of sugar after leaching. Mechanical characteristics were evaluated via compression testing before and after porogen leaching. Bone marrow stromal cells (BMSCs) behavior in the printed scaffolds was studied by assessing viability, metabolic activity, osteo-differentiation, and mineralization. The scaffolds with a 70% sugar concentration exhibited superior printability and reached the highest porosity of 80%, but performed poorly during mechanical testing. A 50% PS concentration demonstrated a 70% porosity, with an average pore size of 25 µm, favoring cell attachment. No trace of sucrose was found in Raman after leaching the sugar for 8 hours. Water contact angle results show improved hydrophilicity as the sugar concentration increased, making the scaffolds more conductive to cell adhesion. The behavior of bone marrow stromal cells (BMSCs) showed positive viability and proliferation results with an increasing trend of mineralization and osteo-differentiation as the sucrose concentration increased. The addition of HA and DEX also promoted mineralization and osteo-differentiation in the cultures. The integration of PS as porogen at a concentration of 50%wt within PCL scaffolds presents a promising approach to address the poor cell attachment and tissue integration issues of PCL in bone tissue engineering. The method allows for the fabrication of scaffolds with tunable porosity and mechanical properties, suitable for various applications. The addition of HA and DEX further enhanced the scaffolds. Future studies will apply the scaffolds in an in-vivo model to thoroughly investigate their performance.

Keywords: bone, PCL, 3D printing, tissue engineering

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Authors: Ildiko Fekete-Kertesz, Jade Chaker, Sylvain Berthelot, Viktoria Feigl, Monika Molnar, Lidia Favier

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There has been growing concern about emerging micropollutants in recent years, because of the possible environmental and health risk posed by these substances, which are released into the environment as a consequence of anthropogenic activities. Among them pharmaceuticals are currently not considered under water quality regulations; however, their potential effect on the environment have become more frequent in recent years. Due to the fact that these compounds can be detected in natural water matrices, it can be concluded, that the currently applied water treatment processes are not efficient enough for their effective elimination. To date, advanced oxidation processes (AOPs) are considered as highly competitive water treatment technologies for the removal of those organic micropollutants not treatable by conventional techniques due to their high chemical stability and/or low biodegradability. AOPs such as (photo)chemical oxidation and heterogeneous photocatalysis have proven their potential in degrading harmful organic compounds from aqueous matrices. However, some of these technologies generate reaction by-products, which can even be more toxic to aquatic organisms than the parent compounds. Thus, target compound removal does not necessarily result in the removal of toxicity. Therefore, to evaluate process efficiency the determination of the toxicity and ecotoxicity of the reaction intermediates is crucial to estimate the environmental risk of such techniques. In this context, the present study investigates the effectiveness of TiO2 assisted photodegradation for the removal of emerging water contaminants. Two drugs named losartan (used in high blood pressure medication) and levetiracetam (used to treat epilepsy) were considered in this work. The photocatalytic reactions were carried out with a commercial catalyst usually employed in photocatalysis. Moreover, the toxicity of the by-products generated during the process was assessed with various ecotoxicological methods applying aquatic test organisms from different trophic levels. A series of experiments were performed to evaluate the toxicity of untreated and treated solutions applying the Aliivibrio fischeri bioluminescence inhibition test, the Tetrahymena pyriformis proliferation inhibition test, the Daphnia magna lethality and immobilization tests and the Lemna minor growth inhibition test. The applied ecotoxicological methodology indicated sensitively the toxic effects of the treated and untreated water samples, hence the applied test battery is suitable for the ecotoxicological characterization of TiO2 based photocatalytic water treatment technologies and the indication of the formation of toxic by-products from the parent chemical compounds. Obtained results clearly showed that the TiO2 assisted photodegradation was more efficient in the elimination of losartan than levetiracetam. It was also observed that the treated levetiracetam solutions had more severe effect on the applied test organisms. A possible explanation would be the production of levetiracetam by-products, which are more toxic than the parent compound. The increased toxicity and the risk of formation of toxic metabolites represent one possible limitation to the implementation of photocatalytic treatment using TiO2 for the removal of losartan and levetiracetam. Our results proved that, the battery of ecotoxicity tests used in this work can be a promising investigation tool for the environmental risk assessment of photocatalytic processes.

Keywords: aquatic micropollutants, ecotoxicology, nano titanium dioxide, photocatalysis, water treatment

Procedia PDF Downloads 164

Authors: Francesca Gullo, Paola Palmero, Massimo Messori

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Transparent wood is considered a promising structural material for the development of environmentally friendly, energy-efficient engineered components. To obtain transparent wood from natural wood materials two approaches can be used: i) bottom-up and ii) top-down. Through the second method, the color of natural wood samples is lightened through a chemical bleaching process that acts on chromophore groups of lignin, such as the benzene ring, quinonoid, vinyl, phenolics, and carbonyl groups. These chromophoric units form complex conjugate systems responsible for the brown color of wood. There are two strategies to remove color and increase the whiteness of wood: i) lignin removal and ii) lignin bleaching. In the lignin removal strategy, strong chemicals containing chlorine (chlorine, hypochlorite, and chlorine dioxide) and oxidizers (oxygen, ozone, and peroxide) are used to completely destroy and dissolve the lignin. In lignin bleaching methods, a moderate reductive (hydrosulfite) or oxidative (hydrogen peroxide) is commonly used to alter or remove the groups and chromophore systems of lignin, selectively discoloring the lignin while keeping the macrostructure intact. It is, therefore, essential to manipulate nanostructured wood by precisely controlling the nanopores in the cell walls by monitoring both chemical treatments and process conditions, for instance, the treatment time, the concentration of chemical solutions, the pH value, and the temperature. The elimination of wood light scattering is the second step in the fabrication of transparent wood materials, which can be achieved through two-step approaches: i) the polymer impregnation method and ii) the densification method. For the polymer impregnation method, the wood scaffold is treated with polymers having a corresponding refractive index (e.g., PMMA and epoxy resins) under vacuum to obtain the transparent composite material, which can finally be pressed to align the cellulose fibers and reduce interfacial defects in order to have a finished product with high transmittance (>90%) and excellent light-guiding. However, both the solution-based bleaching and the impregnation processes used to produce transparent wood generally consume large amounts of energy and chemicals, including some toxic or pollutant agents, and are difficult to scale up industrially. Here, we report a method to produce optically transparent wood by modifying the lignin structure with a chemical reaction at room temperature using small amounts of hydrogen peroxide in an alkaline environment. This method preserves the lignin, which results only deconjugated and acts as a binder, providing both a strong wood scaffold and suitable porosity for infiltration of biobased polymers while reducing chemical consumption, the toxicity of the reagents used, polluting waste, petroleum by-products, energy and processing time. The resulting transparent wood demonstrates high transmittance and low thermal conductivity. Through the combination of process efficiency and scalability, the obtained materials are promising candidates for application in the field of construction for modern energy-efficient buildings.

Keywords: bleached wood, energy-efficient components, hydrogen peroxide, transparent wood, wood composites

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Authors: Mohammed S. Razali, Kamel Khimeche, Dahah Hichem, Ammar Boudjellal, Djamel E. Kaderi, Nourddine Ramdani

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The use of additive manufacturing technologies has revolutionized various aspects of our daily lives. In particular, 3D printing has greatly advanced biomedical applications. While fused filament fabrication (FFF) technologies have made it easy to produce or prototype various medical devices, it is crucial to minimize the risk of contamination. New materials with antibacterial properties, such as those containing compounded silver nanoparticles, have emerged on the market. In a previous study, we prepared a newly sintered seashell filler (SSh) from bio-based seashells found along the Mediterranean coast using a suitable heat treatment process. We then prepared a series of polylactic acid (PLA) and polybutylene succinate (PBS) biocomposites filled with these SSh particles using a melt mixing technique with a twin-screw extruder to use them as feedstock filaments for 3D printing. The study consisted of two parts: evaluating the antibacterial activity of newly prepared biocomposites made of PLA and PBS reinforced with a sintered seashell in the first part and experimental and modeling analysis of the non-isothermal crystallization kinetics of these biocomposites in the second part. In the first part, the bactericidal activity of the biocomposites against three different bacteria, including Gram-negative bacteria such as (E. coli and Pseudomonas aeruginosa), as well as Gram-positive bacteria such as (Staphylococcus aureus), was examined. The PLA-based biocomposite containing 20 wt.% of SSh particles exhibited an inhibition zone with radial diameters of 8mm and 6mm against E. coli and Pseudo. Au, respectively, while no bacterial activity was observed against Staphylococcus aureus. In the second part, the focus was on investigating the effect of the sintered seashell filler particles on the non-isothermal crystallization kinetics of PLA and PBS 3D-printing composite materials. The objective was to understand the impact of the filler particles on the crystallization mechanism of both PLA and PBS during the cooling process of a melt-extruded filament in (FFF) to manage the dimensional accuracy and mechanical properties of the final printed part. We conducted a non-isothermal melt crystallization kinetic study of a series of PLA-SS and PBS-SS composites using differential scanning calorimetry at various cooling rates. We analyzed the obtained kinetic data using different crystallization kinetic models such as modified Avrami, Ozawa, and Mo's methods. Dynamic mode describes the relative crystallinity as a function of temperature; it found that time half crystallinity (t1/2) of neat PLA decreased from 17 min to 7.3 min for PLA+5 SSh and the (t1/2) of virgin PBS was reduced from 3.5 min to 2.8 min for the composite containing 5wt.% of SSh. We found that the coated SS particles with stearic acid acted as nucleating agents and had a nucleation activity, as observed through polarized optical microscopy. Moreover, we evaluated the effective energy barrier of the non-isothermal crystallization process using the Iso conversional methods of Flynn-Wall-Ozawa (F-W-O) and Kissinger-Akahira-Sunose (K-A-S). The study provides significant insights into the crystallization behavior of PLA and PBS biocomposites.

Keywords: avrami model, bio-based reinforcement, dsc, gram-negative bacteria, gram-positive bacteria, isoconversional methods, non-isothermal crystallization kinetics, poly(butylene succinate), poly(lactic acid), antbactirial activity

Procedia PDF Downloads 45

Authors: Eliska Smidova, Petr Kabele

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This paper describes non-linear finite element simulation of laminated veneer lumber (LVL) under tensile and shear loads that induce cracking along fibers. For this purpose, we use 2D homogeneous orthotropic constitutive model of tensile and shear fracture in timber that has been recently developed and implemented into ATENA® finite element software by the authors. The model captures (i) material orthotropy for small deformations in both linear and non-linear range, (ii) elastic behavior until anisotropic failure criterion is fulfilled, (iii) inelastic behavior after failure criterion is satisfied, (iv) different post-failure response for cracks along and across the grain, (v) unloading/reloading behavior. The post-cracking response is treated by fixed smeared crack model where Reinhardt-Hordijk function is used. The model requires in total 14 input parameters that can be obtained from standard tests, off-axis test results and iterative numerical simulation of compact tension (CT) or compact tension-shear (CTS) test. New engineered timber composites, such as laminated veneer lumber (LVL), offer improved structural parameters compared to sawn timber. LVL is manufactured by laminating 3 mm thick wood veneers aligned in one direction using water-resistant adhesives (e.g. polyurethane). Thus, 3 main grain directions, namely longitudinal (L), tangential (T), and radial (R), are observed within the layered LVL product. The core of this work consists in 3 numerical simulations of experiments where Radiata Pine LVL and Yellow Poplar LVL were involved. The first analysis deals with calibration and validation of the proposed model through off-axis tensile test (at a load-grain angle of 0°, 10°, 45°, and 90°) and CTS test (at a load-grain angle of 30°, 60°, and 90°), both of which were conducted for Radiata Pine LVL. The second finite element simulation reproduces load-CMOD curve of compact tension (CT) test of Yellow Poplar with the aim of obtaining cohesive law parameters to be used as an input in the third finite element analysis. That is four point bending test of small-size arch of 780 mm span that is made of Yellow Poplar LVL. The arch is designed with a through crack between two middle layers in the crown. Curved laminated beams are exposed to high radial tensile stress compared to timber strength in radial tension in the crown area. Let us note that in this case the latter parameter stands for tensile strength in perpendicular direction with respect to the grain. Standard tests deliver most of the relevant input data whereas traction-separation law for crack along the grain can be obtained partly by inverse analysis of compact tension (CT) test or compact tension-shear test (CTS). The initial crack was modeled as a narrow gap separating two layers in the middle the arch crown. Calculated load-deflection curve is in good agreement with the experimental ones. Furthermore, crack pattern given by numerical simulation coincides with the most important observed crack paths.

Keywords: compact tension (CT) test, compact tension shear (CTS) test, fixed smeared crack model, four point bending test, laminated arch, laminated veneer lumber LVL, off-axis test, orthotropic elasticity, orthotropic fracture criterion, Radiata Pine LVL, traction-separation law, yellow poplar LVL, 2D constitutive model

Procedia PDF Downloads 253

Authors: Kashima Arora, Monika Tomar, Vinay Gupta

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Biosensors have found potential applications ranging from environmental testing and biowarfare agent detection to clinical testing, health care, and cell analysis. This is driven in part by the desire to decrease the cost of health care and to obtain precise information more quickly about the health status of patient by the development of various biosensors, which has become increasingly prevalent in clinical testing and point of care testing for a wide range of biological elements. Uric acid is an important byproduct in human body and a number of pathological disorders are related to its high concentration in human body. In past few years, rapid growth in the development of new materials and improvements in sensing techniques have led to the evolution of advanced biosensors. In this context, metal oxide thin film based matrices due to their bio compatible nature, strong adsorption ability, high isoelectric point (IEP) and abundance in nature have become the materials of choice for recent technological advances in biotechnology. In the past few years, wide band-gap metal oxide semiconductors including ZnO, SnO₂ and CeO₂ have gained much attention as a matrix for immobilization of various biomolecules. Tin oxide (SnO₂), wide band gap semiconductor (Eg =3.87 eV), despite having multifunctional properties for broad range of applications including transparent electronics, gas sensors, acoustic devices, UV photodetectors, etc., it has not been explored much for biosensing purpose. To realize a high performance miniaturized biomolecular electronic device, rf sputtering technique is considered to be the most promising for the reproducible growth of good quality thin films, controlled surface morphology and desired film crystallization with improved electron transfer property. Recently, iron oxide and its composites have been widely used as matrix for biosensing application which exploits the electron communication feature of Fe, for the detection of various analytes using urea, hemoglobin, glucose, phenol, L-lactate, H₂O₂, etc. However, to the authors’ knowledge, no work is being reported on modifying the electronic properties of SnO₂ by implanting with suitable metal (Fe) to induce the redox couple in it and utilizing it for reagentless detection of uric acid. In present study, Fe implanted SnO₂ based matrix has been utilized for reagentless uric acid biosensor. Implantation of Fe into SnO₂ matrix is confirmed by energy-dispersive X-Ray spectroscopy (EDX) analysis. Electrochemical techniques have been used to study the response characteristics of Fe modified SnO₂ matrix before and after uricase immobilization. The developed uric acid biosensor exhibits a high sensitivity to about 0.21 mA/mM and a linear variation in current response over concentration range from 0.05 to 1.0 mM of uric acid besides high shelf life (~20 weeks). The Michaelis-Menten kinetic parameter (Km) is found to be relatively very low (0.23 mM), which indicates high affinity of the fabricated bioelectrode towards uric acid (analyte). Also, the presence of other interferents present in human serum has negligible effect on the performance of biosensor. Hence, obtained results highlight the importance of implanted Fe:SnO₂ thin film as an attractive matrix for realization of reagentless biosensors towards uric acid.

Keywords: Fe implanted tin oxide, reagentless uric acid biosensor, rf sputtering, thin film

Procedia PDF Downloads 147

Authors: Reham K. Sebaih, Afaf I. Shehata , Awatif A. Hindi, Tarek Gheith, Amal A. Hazzani Anas Al-Orjan

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Staphylococci spp are ubiquitous gram-positive bacteria is often associated with infections, especially nosocomial infections, and antibiotic resistanceStudy pathogenic bacteria and its use as a tool in the technology of Nano biology and molecular genetics research of the latest research trends of modern characterization and definition of different multiresistant of bacteria including Staphylococci. The Staphylococci are widespread all over the world and particularly in Saudi Arabia The present work study was conducted to evaluate the effect of five different types of nanoparticles (biosynthesized zinc oxide, Spherical and rod of each silver and gold nanoparticles) and their antibacterial impact on the Staphylococcus species. Ninety-six isolates of Staphylococcus species. Staphylococcus aureus, Staphylococcus epidermidis, MRSA were collected from different sources during the period between March 2011G to June 2011G. All isolates were isolated from inpatients and outpatients departments at Royal Commission Hospital in Yanbu Industrial, Saudi Arabia. High percentage isolation from males(55%) than females (45%). Staphylococcus epidermidis from males was (47%), (28%), and(25%). For Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus (MRSA. Isolates from females were Staphylococcus aureus with higher percent of (47%), (30%), and (23%) for MRSA, Staphylococcus epidermidis. Staphylococcus aureus from wound swab were the highest percent (51.42%) followed by vaginal swab (25.71%). Staphylococcus epidermidis were founded with higher percentage in blood (37.14%) and wound swab (34.21%) respectively related to other. The highest percentage of methicillin-resistant Staphylococcus aureus (MRSA)(80.77%) were isolated from wound swab, while those from nostrils were (19.23%). Staphylococcus species were isolates in highest percentage from hospital Emergency department with Staphylococcus aureus (59.37%), Methicillin-resistant Staphylococcus aureus (MRSA) (28.13%)and Staphylococcus epidermidis (12.5%) respectively. Evaluate the antibacterial property of Zinc oxide, Silver, and Gold nanoparticles as an alternative to conventional antibacterial agents Staphylococci isolates from hospital sources we screened them. Gold and Silver rods Nanoparticles to be sensitive to all isolates of Staphylococcus species. Zinc oxide Nanoparticles gave sensitivity impact range(52%) and (48%). The Gold and Silver spherical nanoparticles did not showed any effect on Staphylococci species. Zinc Oxide Nanoparticles gave bactericidal impact (25%) and bacteriostatic impact (75%) for of Staphylococci species. Detecting the association of nanoparticles with Staphylococci isolates imaging by scanning electron microscope (SEM) of some bacteriostatic isolates for Zinc Oxide nanoparticles on Staphylococcus aureus, Staphylococcus epidermidis and Methicillin resistant Staphylococcus aureus(MRSA), showed some Overlapping Bacterial cells with lower their number and appearing some appendages with deformities in external shape. Molecular analysis was applied by Multiplex polymerase chain reaction (PCR) used for the identification of genes within Staphylococcal pathogens. A multiplex polymerase chain reaction (PCR) method has been developed using six primer pairs to detect different genes using 50bp and 100bp DNA ladder marker. The range of Molecular gene typing ranging between 93 bp to 326 bp for Staphylococcus aureus and Methicillin resistant Staphylococcus aureus by TSST-1,mecA,femA and eta, while the bands border were from 546 bp to 682 bp for Staphylococcus epidermidis using icaAB and atlE. Sixteen isolation of Staphylococcus aureus and Methicillin resistant Staphylococcus aureus were positive for the femA gene at 132bp,this allowed the using of this gene as an internal positive control, fifteen isolates of Staphylococcus aureus and Methicillin resistant Staphylococcus aureus were positive for mecA gene at163bp.This gene was responsible for antibiotic resistant Methicillin, Two isolates of Staphylococcus aureus and Methicillin resistant Staphylococcus aureus were positive for the TSST-1 gene at326bp which is responsible for toxic shock syndrome in some Staphylococcus species, None were positive for eta gene at 102bpto that was responsible for Exfoliative toxins. Six isolates of Staphylococcus epidermidis were positive for atlE gene at 682 bp which is responsible for the initial adherence, three isolates of Staphylococcus epidermidis were positive for icaAB gene at 546bp that are responsible for mediates the formation of the biofilm. In conclusion, this study demonstrates the ability of the detection of the genes to discriminate between infecting Staphylococcus strains and considered biological tests, they may potentiate the clinical criteria used for the diagnosis of septicemia or catheter-related infections.

Keywords: multiplex polymerase chain reaction, toxic shock syndrome, Staphylococcus aureus, nosocomial infections

Procedia PDF Downloads 309

Authors: Michael Sigruener, Dirk Muscat, Nicole Struebbe

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Fiber reinforcement is a state of the art to enhance mechanical properties in plastics. For concrete and civil engineering, steel reinforcements are commonly used. Steel reinforcements show disadvantages in their chemical resistance and weight, whereas polymer fibers' major problems are in fiber-matrix adhesion and mechanical properties. In spite of these facts, longevity and easy handling, as well as chemical resistance motivate researches to develop a polymeric material for fiber reinforced concrete. Adhesion and interfacial mechanism in fiber-polymer-composites are already studied thoroughly. For polymer fibers used as concrete reinforcement, the bonding behavior still requires a deeper investigation. Therefore, several differing polymers (e.g., polypropylene (PP), polyamide 6 (PA6) and polyetheretherketone (PEEK)) were spun into fibers via single screw extrusion and monoaxial stretching. Fibers then were embedded in a concrete matrix, and Single-Fiber-Pull-Out-Tests (SFPT) were conducted to investigate bonding characteristics and microstructural interface of the composite. Differences in maximum pull-out-force, displacement and slope of the linear part of force vs displacement-function, which depicts the adhesion strength and the ductility of the interfacial bond were studied. In SFPT fiber, debonding is an inhomogeneous process, where the combination of interfacial bonding and friction mechanisms add up to a resulting value. Therefore, correlations between polymeric properties and pull-out-mechanisms have to be emphasized. To investigate these correlations, all fibers were introduced to a series of analysis such as differential scanning calorimetry (DSC), contact angle measurement, surface roughness and hardness analysis, tensile testing and scanning electron microscope (SEM). Of each polymer, smooth and abraded fibers were tested, first to simulate the abrasion and damage caused by a concrete mixing process and secondly to estimate the influence of mechanical anchoring of rough surfaces. In general, abraded fibers showed a significant increase in maximum pull-out-force due to better mechanical anchoring. Friction processes therefore play a major role to increase the maximum pull-out-force. The polymer hardness affects the tribological behavior and polymers with high hardness lead to lower surface roughness verified by SEM and surface roughness measurements. This concludes into a decreased maximum pull-out-force for hard polymers. High surface energy polymers show better interfacial bonding strength in general, which coincides with the conducted SFPT investigation. Polymers such as PEEK or PA6 show higher bonding strength in smooth and roughened fibers, revealed through high pull-out-force and concrete particles bonded on the fiber surface pictured via SEM analysis. The surface energy divides into dispersive and polar part, at which the slope is correlating with the polar part. Only polar polymers increase their SFPT-function slope due to better wetting abilities when showing a higher bonding area through rough surfaces. Hence, the maximum force and the bonding strength of an embedded fiber is a function of polarity, hardness, and consequently surface roughness. Other properties such as crystallinity or tensile strength do not affect bonding behavior. Through the conducted analysis, it is now feasible to understand and resolve different effects in pull-out-behavior step-by-step based on the polymer properties itself. This investigation developed a roadmap on how to engineer high adhering polymeric materials for fiber reinforcement of concrete.

Keywords: fiber-matrix interface, polymeric fibers, fiber reinforced concrete, single fiber pull-out test

Procedia PDF Downloads 85

Authors: James Forren

Abstract:

This research paper details a recent demonstrator project in which digital form found textile structures were built by human craftspersons wearing augmented reality (AR) head-worn displays (HWDs). The project utilized a wet-state natural fiber / cementitious matrix composite to generate minimal bending shapes in tension which, when cured and rotated, performed as minimal-bending compression members. The significance of the project is that it synthesizes computational structural simulations with visually guided handcraft production. Computational and physical form-finding methods with textiles are well characterized in the development of architectural form. One difficulty, however, is physically building computer simulations: often requiring complicated digital fabrication workflows. However, AR HWDs have been used to build a complex digital form from bricks, wood, plastic, and steel without digital fabrication devices. These projects utilize, instead, the tacit knowledge motor schema of the human craftsperson. Computational simulations offer unprecedented speed and performance in solving complex structural problems. Human craftspersons possess highly efficient complex spatial reasoning motor schemas. And textiles offer efficient form-generating possibilities for individual structural members and overall structural forms. This project proposes that the synthesis of these three modalities of structural problem-solving – computational, human, and material - may not only develop efficient structural form but offer further creative potentialities when the respective intelligence of each modality is productively leveraged. The project methodology pertains to its three modalities of production: 1) computational, 2) human, and 3) material. A proprietary three-dimensional graphic statics simulator generated a three-legged arch as a wireframe model. This wireframe was discretized into nine modules, three modules per leg. Each module was modeled as a woven matrix of one-inch diameter chords. And each woven matrix was transmitted to a holographic engine running on HWDs. Craftspersons wearing the HWDs then wove wet cementitious chords within a simple falsework frame to match the minimal bending form displayed in front of them. Once the woven components cured, they were demounted from the frame. The components were then assembled into a full structure using the holographically displayed computational model as a guide. The assembled structure was approximately eighteen feet in diameter and ten feet in height and matched the holographic model to under an inch of tolerance. The construction validated the computational simulation of the minimal bending form as it was dimensionally stable for a ten-day period, after which it was disassembled. The demonstrator illustrated the facility with which computationally derived, a structurally stable form could be achieved by the holographically guided, complex three-dimensional motor schema of the human craftsperson. However, the workflow traveled unidirectionally from computer to human to material: failing to fully leverage the intelligence of each modality. Subsequent research – a workshop testing human interaction with a physics engine simulation of string networks; and research on the use of HWDs to capture hand gestures in weaving seeks to develop further interactivity with rope and chord towards a bi-directional workflow within full-scale building environments.

Keywords: augmented reality, cementitious composites, computational form finding, textile structures

Procedia PDF Downloads 138

Authors: Qiaosi Li, Frankie Kwan Kit Wong, Tung Fung

Abstract:

Lightweight unmanned aerial vehicle (UAV) loading with novel sensors offers a low cost approach for data acquisition in complex environment. This study established a framework for applying UAV system in complex environment quick mapping and assessed the performance of UAV-based hyperspectral image and digital surface model (DSM) derived from photogrammetric point clouds for 13 species classification in wetland area Mai Po Inner Deep Bay Ramsar Site, Hong Kong. The study area was part of shallow bay with flat terrain and the major species including reedbed and four mangroves: Kandelia obovata, Aegiceras corniculatum, Acrostichum auerum and Acanthus ilicifolius. Other species involved in various graminaceous plants, tarbor, shrub and invasive species Mikania micrantha. In particular, invasive species climbed up to the mangrove canopy caused damage and morphology change which might increase species distinguishing difficulty. Hyperspectral images were acquired by Headwall Nano sensor with spectral range from 400nm to 1000nm and 0.06m spatial resolution image. A sequence of multi-view RGB images was captured with 0.02m spatial resolution and 75% overlap. Hyperspectral image was corrected for radiative and geometric distortion while high resolution RGB images were matched to generate maximum dense point clouds. Furtherly, a 5 cm grid digital surface model (DSM) was derived from dense point clouds. Multiple feature reduction methods were compared to identify the efficient method and to explore the significant spectral bands in distinguishing different species. Examined methods including stepwise discriminant analysis (DA), support vector machine (SVM) and minimum noise fraction (MNF) transformation. Subsequently, spectral subsets composed of the first 20 most importance bands extracted by SVM, DA and MNF, and multi-source subsets adding extra DSM to 20 spectrum bands were served as input in maximum likelihood classifier (MLC) and SVM classifier to compare the classification result. Classification results showed that feature reduction methods from best to worst are MNF transformation, DA and SVM. MNF transformation accuracy was even higher than all bands input result. Selected bands frequently laid along the green peak, red edge and near infrared. Additionally, DA found that chlorophyll absorption red band and yellow band were also important for species classification. In terms of 3D data, DSM enhanced the discriminant capacity among low plants, arbor and mangrove. Meanwhile, DSM largely reduced misclassification due to the shadow effect and morphological variation of inter-species. In respect to classifier, nonparametric SVM outperformed than MLC for high dimension and multi-source data in this study. SVM classifier tended to produce higher overall accuracy and reduce scattered patches although it costs more time than MLC. The best result was obtained by combining MNF components and DSM in SVM classifier. This study offered a precision species distribution survey solution for inaccessible wetland area with low cost of time and labour. In addition, findings relevant to the positive effect of DSM as well as spectral feature identification indicated that the utility of UAV-borne hyperspectral and photogrammetry deriving 3D data is promising in further research on wetland species such as bio-parameters modelling and biological invasion monitoring.

Keywords: digital surface model (DSM), feature reduction, hyperspectral, photogrammetric point cloud, species mapping, unmanned aerial vehicle (UAV)

Procedia PDF Downloads 229

Authors: Mirijam Vrabec, Marian Janak, Bojan Ambrozic, Angelja K. Surca, Nastja Rogan Smuc, Nina Zupancic, Saso Sturm

Abstract:

Natural microdiamonds and moissanite (SiC) can form during the orogenic events under ultrahigh-pressure metamorphic conditions (UHP), when parts of Earth’s crust are subducted to extreme depths. So far, such processes were identified only in few places on the Earth, and therefore, represent unique opportunity to study the evolution of the Earth’s deep interior. An important discovery of microdiamonds and moissanite was reported from Pohorje, (Slovenia), where they occurred as single or polyphase inclusions in garnets. Metasedimentary rocks from Pohorje are predominantly gneisses representing parts of the Austroalpine metamorphic units of the Eastern Alps. During Cretaceous orogeny, (ca. 95–92 Ma) continental crustal rocks were deeply subducted to the mantle depths (below 100 km) and metamorphosed at pressures exceeding 3.5 GPa and temperatures between 800–850 °C. Microstructural and phase analysis of the inclusions as well as detailed elemental analysis of host garnets were carried out combining several analytical techniques: optical microscope in plane polarized transmitted light, electron probe microanalysis (EPMA) with wavelength-dispersive x-ray spectrometry (WDS) and field-emission scanning microscope (FEG-SEM) with energy-dispersive x-ray spectroscopy (EDS). Micro-Raman analysis revealed sharp, first order diamond bands sometimes accompanied by graphite bands implying that transformation of diamond back to graphite occurred. To study the chemical and crystallographic relationship between microdiamonds and co-inclusions, advanced techniques of transmission electron microscopy (TEM) were applied, which included high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM), combined with EDS and electron energy-loss spectroscopy (EELS). To prepare electron transparent TEM lamellae selectively a dual-beam Focused Ion Beam/SEM (FIB/SEM) was employed. Detailed study of TEM lamellae, which was cross-sectioned from the highly faceted inclusion body located within the host garnet crystal matrix, revealed rich and rather complex internal structure. Namely, the negative crystal facets of the main inclusion body were typically decorated with up to 1 μm thick amorphous layer, reflecting the general garnet composition with slight variations in Fe/Ca content. Within these layers, ELNES analysis revealed the presence of a 28–30 nm thick layer of amorphous carbon. The very last section of this layer corresponds to composition of SiO2. Within the inclusion, besides diamond and moissanite alumosilicate mineral with pronounced layered structure, iron sulfides and chlorine were identified under TEM and CO2 and CH4 using Raman. Moissanite is found as single crystal or composed from numerous highly textured nano-crystals with the average size of 10 nm. Moissanite inclusions were found embedded inside the amorphous crust implying that moissanite crystalized well before the deposition of the amorphous layer. From the microstructural, crystallographic and chemical observations so far we can deduce, that polyphase inclusions in diamond bearing garnets from Pohorje most probably crystallized from reduced supercritical fluids. Based on layered interface structure of the host mineral multiphase process of crystallization is possible. The presence of microdiamonds and moissanite in rocks from Pohorje demonstrates that these parts of the Eastern Alps were subducted to extreme depths, and were subsequently exhumed back to the Earth's surface without complete breakdown of UHP mineral phases, allowing a rear and exceptional opportunity to study them in-situ.

Keywords: diamond, fluid inclusions, moissanite, TEM, UHP metamorphism.

Procedia PDF Downloads 273

Authors: Z. S. Haidar

Abstract:

Millions of teeth are removed annually, and dental extraction is one of the most commonly performed surgical procedures globally. Whether due to caries, periodontal disease, or trauma, exodontia and the ensuing wound healing and bone remodeling processes of the resultant socket (hole in the jaw bone) usually result in serious deformities of the residual alveolar osseous ridge and surrounding soft tissues (reduced height/width). Such voluminous changes render the placement of a proper conventional bridge, denture, or even an implant-supported prosthesis extremely challenging. Further, most extractions continue to be performed with no regard for preventing the onset of alveolar osteitis (also known as dry socket, a painful and difficult-to-treat/-manage condition post-exodontia). Hence, such serious resorptive morphological changes often result in significant facial deformities and a negative impact on the overall Quality of Life (QoL) of patients (and oral health-related QoL); alarming, particularly for the geriatric with compromised healing and in light of the thriving longevity statistics. Despite advances in tissue/wound grafting, serious limitations continue to exist, including efficacy and clinical outcome predictability, cost, treatment time, expertise, and risk of immune reactions. For cases of dry socket, specifically, the commercially available and often-prescribed home remedies are highly-lacking. Indeed, most are not recommended for use anymore. Alveogyl is a fine example. Hence, there is a great market demand and need for alternative solutions. Herein, SockGEL/PLUG (patent pending), an innovative, all-natural, drug-free, and injectable thermo-responsive hydrogel, was designed, formulated, characterized, and evaluated as an osteogenic, angiogenic, anti-microbial, and pain-soothing suture-free intra-alveolar dressing, safe and efficacious for use in fresh extraction sockets, immediately post-exodontia. It is composed of FDA-approved, biocompatible and biodegradable polymers, self-assembled electro-statically to formulate a scaffolding matrix to (1) prevent the on-set of alveolar osteitis via securing the fibrin-clot in situ and protecting/sealing the socket from contamination/infection; and (2) endogenously promote/accelerate wound healing and bone remodeling to preserve the volume of the alveolus. The intrinsic properties of the SockGEL/PLUG hydrogel were evaluated physical-chemical-mechanically for safety (cell viability), viscosity, rheology, bio-distribution, and essentially, capacity to induce wound healing and osteogenesis (small defect, in vivo) without any signaling cues from exogenous cells, growth factors or drugs. The proposed animal model of cranial critical-sized and non-vascularized bone defects shall provide new and critical insights into the role and mechanism of the employed natural bio-polymer blend and gel product in endogenous reparative regeneration of soft tissues and bone morphogenesis. Alongside, the fine-tuning of our modified formulation method will further tackle appropriateness, reproducibility, scalability, ease, and speed in producing stable, biodegradable, and sterilizable thermo-sensitive matrices (3-dimensional interpenetrating yet porous polymeric network) suitable for the intra-socket application. Findings are anticipated to provide sufficient evidence to translate into pilot clinical trials and validate the innovation before engaging the market for feasibility, acceptance, and cost-effectiveness studies.

Keywords: hydrogel, nanotechnology, bioengineering, bone regeneration, nanogel, drug delivery

Procedia PDF Downloads 83

Authors: Ziyad S. Haidar

Abstract:

Background: Saliva plays a major role in maintaining oral, dental, and general health and well-being; where it normally bathes the oral cavity acting as a clearing agent. This becomes more apparent when the amount and quality of saliva are significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the 5th most common malignancy worldwide, during which the salivary glands are included within the radiation field/zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely as they become malnourished and experience a significant decrease in their QoL. Accordingly, the formulation of a radio-protection/-prevention modality and development of an alternative Rx to restore damaged salivary gland tissue is eagerly awaited and highly desirable. Objectives: Assess the pre-clinical radio-protective effect and reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs, followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: cancer, head and neck, oncology, drug development, drug delivery systems, nanotechnology, nanoncology

Procedia PDF Downloads 46

Authors: Ziyad S. Haidar

Abstract:

Background: Saliva plays a major role in maintaining oral and dental health (consequently, general health and well-being). Where it normally bathes the oral cavity and acts as a clearing agent. This becomes more apparent when the amount and quality of salivare significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the fifth most common malignancy worldwide, during which the salivary glands are included within the radiation field or zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely because they become malnourished and experience a significant decrease in their quality of life. Accordingly, the development of an alternative treatment to restore or regenerate damaged salivary gland tissue is eagerly awaited. Likewise, the formulation of a radioprotection modality and early damage prevention strategy is also highly desirable. Objectives: To assess the pre-clinical radio-protective effect as well as the reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned in this experimental work for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs (in solution and powder formats), followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy (revised from our previous 15Gy model) was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: saliva, head and neck cancer, nanotechnology, controlled drug delivery, xerostomia, mucositis, biopolymers, innovation

Procedia PDF Downloads 55