Search results for: biocompatibility
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 269

Search results for: biocompatibility

89 A Fluid-Walled Microfluidic Device for Cell Migration Studies

Authors: Cyril Deroy, Agata Rumianek, David R. Greaves, Peter R. Cook, Edmond J. Walsh

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Various microfluidic platforms have been developed in the past couple of decades offering experimental methods for the study of cell migration; however, their implementation in the laboratory has remained limited. Some reasons cited for the lack of uptake include the technical complexity of the devices, high failure rate associated with gas-bubbles, biocompatibility concerns with the use of polydimethylsiloxane (PDMS) and equipment/time/expertise requirements for operation and manufacture. As sample handling remains challenging due to the closed format of microfluidic devices, open microfluidic systems have been developed offering versatility and simplicity of use. Rather than confining fluids by solid walls, samples can be accessed directly over the open platform, by removing at least one of the solid boundaries, such as the cover. In this paper, a method for the fabrication of open fluid-walled microfluidic circuits for cell migration studies is introduced, where only materials commonly used by the life-science community are required; tissue culture dishes and cell media. The simplicity of the method, and ability to retrieve cells of interest are two key features of the method. Both passive and active flow-devices can be created in this way. To demonstrate the versatility of the method a cell migration assay is performed, which requires fabricating circuits for establishing chemical gradients, loading cells and incubating, creating chemical gradients, real time imaging of cell migration and finally retrieval of cells. The open architecture has high fidelity as it eliminates air bubble related failures and enables the precise control of gradients. The ability to fabricate custom microfluidic designs in minutes should make this method suitable for use in a wide range of cell migration studies.

Keywords: chemotaxis, fluid walls, gradient generation, open microfluidics

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88 Adsorptive Membrane for Hemodialysis: Potential, Future Prospection and Limitation of MOF as Nanofillers

Authors: MUSAWIRA IFTIKHAR

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The field of membrane materials is the most dynamic due to the constantly evolving requirements advancement of materials, to address challenges such as biocompatibility, protein-bound uremic toxins, blood coagulation, auto-immune responses, oxidative stress, and poor clearance of uremic toxins. Hemodialysis is a membrane filtration processes that is currently necessary for daily living of the patients with ESRD. Tens of millions of people with ESRD have benefited from hemodialysis over the past 60–70 years, both in terms of safeguarding life and a longer lifespan. Beyond challenges associated with the efficiency and separative properties of the membranes, ensuring hemocompatibility, or the safe circulation of blood outside the body for four hours every two days, remains a persistent challenge. This review explores the ongoing field of metal–Organic Frameworks (MOFs) and their applications in hemodialysis, offering a comprehensive examination of various MOFs employed to address challenges inherent in traditional hemodialysis methodologies. this This review included includes the experimental work done with various MOFs as a filler such as UiO-66, HKUST-1, MIL-101, and ZIF-8, which together lead to improved adsorption capacities for a range of uremic toxins and proteins. Furthermore, this review highlights how effectively MOF-based hemodialysis membranes remove a variety of uremic toxins, including p-cresol, urea, creatinine, and indoxyl sulfate and potential filler choices for the future. Future research efforts should focus on refining synthesis techniques, enhancing toxin selectivity, and investigating the long-term durability of MOF-based membranes. With these considerations, MOFs emerge as transformative materials in the quest to develop advanced and efficient hemodialysis technologies, holding the promise to significantly enhance patient outcomes and redefine the landscape of renal therapy.

Keywords: membrane, hemodailysis, metal organic frameworks, seperation, protein adsorbtion

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87 Quest for an Efficient Green Multifunctional Agent for the Synthesis of Metal Nanoparticles with Highly Specified Structural Properties

Authors: Niharul Alam

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The development of energy efficient, economic and eco-friendly synthetic protocols for metal nanoparticles (NPs) with tailor-made structural properties and biocompatibility is a highly cherished goal for researchers working in the field of nanoscience and nanotechnology. In this context, green chemistry is highly relevant and the 12 principles of Green Chemistry can be explored to develop such synthetic protocols which are practically implementable. One of the most promising green chemical synthetic methods which can serve the purpose is biogenic synthetic protocol, which utilizes non-toxic multifunctional reactants derived from natural, biological sources ranging from unicellular organisms to higher plants that are often characterized as “medicinal plants”. Over the past few years, a plethora of medicinal plants have been explored as the source of this kind of multifunctional green chemical agents. In this presentation, we focus on the syntheses of stable monometallic Au and Ag NPs and also bimetallic Au/Ag alloy NPs with highly efficient catalytic property using aqueous extract of leaves of Indian Curry leaf plat (Murraya koenigii Spreng.; Fam. Rutaceae) as green multifunctional agents which is extensively used in Indian traditional medicine and cuisine. We have also studied the interaction between the synthesized metal NPs and surface-adsorbed fluorescent moieties, quercetin and quercetin glycoside which are its chemical constituents. This helped us to understand the surface property of the metal NPs synthesized by this plant based biogenic route and to predict a plausible mechanistic pathway which may help in fine-tuning green chemical methods for the controlled synthesis of various metal NPs in future. We observed that simple experimental parameters e.g. pH and temperature of the reaction medium, concentration of multifunctional agent and precursor metal ions play important role in the biogenic synthesis of Au NPs with finely tuned structures.

Keywords: green multifunctional agent, metal nanoparticles, biogenic synthesis

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86 Monitoring the Thin Film Formation of Carrageenan and PNIPAm Microgels

Authors: Selim Kara, Ertan Arda, Fahrettin Dolastir, Önder Pekcan

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Biomaterials and thin film coatings play a fundamental role in medical, food and pharmaceutical industries. Carrageenan is a linear sulfated polysaccharide extracted from algae and seaweeds. To date, such biomaterials have been used in many smart drug delivery systems due to their biocompatibility and antimicrobial activity properties. Poly (N-isopropylacrylamide) (PNIPAm) gels and copolymers have also been used in medical applications. PNIPAm shows lower critical solution temperature (LCST) property at about 32-34 °C which is very close to the human body temperature. Below and above the LCST point, PNIPAm gels exhibit distinct phase transitions between swollen and collapsed states. A special class of gels are microgels which can react to environmental changes significantly faster than microgels due to their small sizes. Quartz crystal microbalance (QCM) measurement technique is one of the attractive techniques which has been used for monitoring the thin-film formation process. A sensitive QCM system was designed as to detect 0.1 Hz difference in resonance frequency and 10-7 change in energy dissipation values, which are the measures of the deposited mass and the film rigidity, respectively. PNIPAm microgels with the diameter around few hundred nanometers in water were produced via precipitation polymerization process. 5 MHz quartz crystals with functionalized gold surfaces were used for the deposition of the carrageenan molecules and microgels in the solutions which were slowly pumped through a flow cell. Interactions between charged carrageenan and microgel particles were monitored during the formation of the film layers, and the Sauerbrey masses of the deposited films were calculated. The critical phase transition temperatures around the LCST were detected during the heating and cooling cycles. It was shown that it is possible to monitor the interactions between PNIPAm microgels and biopolymer molecules, and it is also possible to specify the critical phase transition temperatures by using a QCM system.

Keywords: carrageenan, phase transitions, PNIPAm microgels, quartz crystal microbalance (QCM)

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85 Evaluation of κ -Carrageenan Hydrogel Efficiency in Wound-Healing

Authors: Ali Ayatic, Emad Mozaffari, Bahareh Tanhaei, Maryam Khajenoori, Saeedeh Movaghar Khoshkho, Ali Ayati

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The abuse of antibiotics, such as tetracycline (TC), is a great global threat to people and the use of topical antibiotics is a promising tact that can help to solve this problem. Antibiotic therapy is often appropriate and necessary for acute wound infections, while topical tetracycline can be highly efficient in improving the wound healing process in diabetics. Due to the advantages of drug-loaded hydrogels as wound dressing, such as ease of handling, high moisture resistance, excellent biocompatibility, and the ability to activate immune cells to speed wound healing, it was found as an ideal wound treatment. In this work, the tetracycline-loaded hydrogels combining agar (AG) and κ-carrageenan (k-CAR) as polymer materials were prepared, in which span60 surfactant was introduced inside as a drug carrier. The Field Emission Scanning Electron Microscopes (FESEM) and Fourier-transform infrared spectroscopy (FTIR) techniques were employed to provide detailed information on the morphology, composition, and structure of fabricated drug-loaded hydrogels and their mechanical properties, and hydrogel permeability to water vapor was investigated as well. Two types of gram-negative and gram-positive bacteria were used to explore the antibacterial properties of prepared tetracycline-contained hydrogels. Their swelling and drug release behavior was studied using the changing factors such as the ratio of polysaccharides (MAG/MCAR), the span60 surfactant concentration, potassium chloride (KCl) concentration and different release media (deionized water (DW), phosphate-buffered saline (PBS), and simulated wound fluid (SWF)) at different times. Finally, the kinetic behavior of hydrogel swelling was studied. Also, the experimental data of TC release to DW, PBS, and SWF using various mathematical models such as Higuchi, Korsmeyer-Peppas, zero-order, and first-order in the linear and nonlinear modes were evaluated.

Keywords: drug release, hydrogel, tetracycline, wound healing

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84 Multilayered Assembly of Gelatin on Nanofibrous Matrix for 3-D Cell Cultivation

Authors: Ji Un Shin, Wei Mao, Hyuk Sang Yoo

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Electrospinning is a versatile tool for fabricating nano-structured polymeric materials. Gelatin hydrogels are considered to be a good material for cell cultivation because of high water swellability as well as good biocompatibility. Three-dimensional (3-D) cell cultivation is a desirable method of cell cultivation for preparing tissues and organs because cell-to-cell interactions or cell-to-matrix interactions can be much enhanced through this approach. For this reason, hydrogels were widely employed as tissue scaffolds because they can support cultivating cells and tissue in multi-dimensions. Major disadvantages of hydrogel-based cell cultivation include low mechanical properties, lack of topography, which should be enhanced for successful tissue engineering. Herein we surface-immobilized gelatin on the surface of nanofibrous matrix for 3-D cell cultivation in topographical cues added environments. Electrospun nanofibers were electrospun with injection of poly(caprolactone) through a single nozzle syringe. Electrospun meshes were then chopped up with a high speed grinder to fine powders. This was hydrolyzed in optimized concentration of sodium hydroxide solution from 1 to 6 hours and harvested by centrifugation. The freeze-dried powders were examined by scanning electron microscopy (SEM) for revealing the morphology and fibrilar shaped with a length of ca. 20um was observed. This was subsequently immersed in gelatin solution for surface-coating of gelatin, where the process repeated up to 10 times for obtaining desirable coating of gelatin on the surface. Gelatin-coated nanofibrils showed high waterswellability in comparison to the unmodified nanofibrils, and this enabled good dispersion properties of the modified nanofibrils in aqueous phase. The degree of water-swellability was increased as the coating numbers of gelatin increased, however, it did not any meaning result after 10 times of gelatin coating process. Thus, by adjusting the gelatin coating times, we could successfully control the degree of hydrophilicity and water-swellability of nanofibrils.

Keywords: nano, fiber, cell, tissue

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83 Influence of an Octenidine Based Wound Gel on Postoperative Wound Healing and Scarring after Abdominoplasty

Authors: Johannes Matiasek

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Introduction and Aims: Octenidine is a common antiseptic agent in the area of surgical interventions because of its antimicrobial efficacy and outstanding biocompatibility index. We investigate the direct postoperative application of octenilin® on typical procedures in the field of plastic surgery in a prospective, randomized controlled intervention study. The aim of this study is to determine the influence of a direct postoperative application of an octenidine-containing wound gel on wound healing and scarring after abdominoplasty. Material and Methods: In this study, we enrolled 33 patients who underwent abdominoplasty because of medical indications (e.g. Cutis laxa abdominis). To ensure an intraindividual comparison, each patient received both dressings (study-group: octenilin® wound gel; control-group: Omnistrip® dry plaster) immediately after surgery. We evaluate wound-healing tendency, pain during dressing changes and scar formation after two weeks, three, six and twelve months. Regarding scar-evaluation skin-elasticity, sebum on the skin, transepidermal waterloss, skin hydration, melanin content and erythema level were determined with special probes. Furthermore the Vancouver Scar Scale (VSS) and pain level during dressing change are determined. Results: At the time of surgery the mean patient’s age was 44.1 years. On average 5.6 dressing changes were necessary. Wound healing disorders occurred more often in the control-group. In the control-group (dry plaster Omnistrip®) patients reported significantly more pain and superficial skin injuries during dressing changes occurred. Objective scar-evaluation after 3, 6 and 12 months resulted in a significant higher skin-elasticity and significant lower transepidermal water loss in the octenilin® group which is confirmed in the VSS. Conclusion: The immediate postoperative application of the octenidine-containing hydrogel octenilin® after abdominoplasty results in favoured scar formation compared to our actual standard therapy. Less hypertrophic scar formation was observed in the study-group.

Keywords: abdominoplasty, octenidine, scarring, wound healing

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82 Microfluidic Chambers with Fluid Walls for Cell Biology

Authors: Cristian Soitu, Alexander Feuerborn, Cyril Deroy, Alfonso Castrejon-Pita, Peter R. Cook, Edmond J. Walsh

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Microfluidics now stands as an academically mature technology after a quarter of a century research activities have delivered a vast array of proof of concepts for many biological workflows. However, translation to industry remains poor, with only a handful of notable exceptions – e.g. digital PCR, DNA sequencing – mainly because of biocompatibility issues, limited range of readouts supported or complex operation required. This technology exploits the domination of interfacial forces over gravitational ones at the microscale, replacing solid walls with fluid ones as building blocks for cell micro-environments. By employing only materials used by biologists for decades, the system is shown to be biocompatible, and easy to manufacture and operate. The method consists in displacing a continuous fluid layer into a pattern of isolated chambers overlaid with an immiscible liquid to prevent evaporation. The resulting fluid arrangements can be arrays of micro-chambers with rectangular footprint, which use the maximum surface area available, or structures with irregular patterns. Pliant, self-healing fluid walls confine volumes as small as 1 nl. Such fluidic structures can be reconfigured during the assays, giving the platform an unprecedented level of flexibility. Common workflows in cell biology are demonstrated – e.g. cell growth and retrieval, cloning, cryopreservation, fixation and immunolabeling, CRISPR-Cas9 gene editing, and proof-of-concept drug tests. This fluid-shaping technology is shown to have potential for high-throughput cell- and organism-based assays. The ability to make and reconfigure on-demand microfluidic circuits on standard Petri dishes should find many applications in biology, and yield more relevant phenotypic and genotypic responses when compared to standard microfluidic assays.

Keywords: fluid walls, micro-chambers, reconfigurable, freestyle

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81 Foamability and Foam Stability of Gelatine-Sodium Dodecyl Sulfate Solutions

Authors: Virginia Martin Torrejon, Song Hang

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Gelatine foams are widely explored materials due to their biodegradability, biocompatibility, and availability. They exhibit outstanding properties and are currently subject to increasing scientific research due to their potential use in different applications, such as biocompatible cellular materials for biomedical products or biofoams as an alternative to fossil-fuel-derived packaging. Gelatine is a highly surface-active polymer, and its concentrated solutions usually do not require surfactants to achieve low surface tension. Still, anionic surfactants like sodium dodecyl sulfate (SDS) strongly interact with gelatine, impacting its viscosity and rheological properties and, in turn, their foaming behaviour. Foaming behaviour is a key parameter for cellular solids produced by mechanical foaming as it has a significant effect on the processing and properties of cellular materials. Foamability mainly impacts the density and the mechanical properties of the foams, while foam stability is crucial to achieving foams with low shrinkage and desirable pore morphology. This work aimed to investigate the influence of SDS on the foaming behaviour of concentrated gelatine foams by using a dynamic foam analyser. The study of maximum foam height created, foam formation behaviour, drainage behaviour, and foam structure with regard to bubble size and distribution were carried out in 10 wt% gelatine solutions prepared at different SDS/gelatine concentration ratios. Comparative rheological and viscometry measurements provided a good correlation with the data from the dynamic foam analyser measurements. SDS incorporation at optimum dosages and gelatine gelation led to highly stable foams at high expansion ratios. The viscosity increase of the hydrogel solution at SDS content increased was a key parameter for foam stabilization. In addition, the impact of SDS content on gelling time and gel strength also considerably impacted the foams' stability and pore structure.

Keywords: dynamic foam analyser, gelatine foams stability and foamability, gelatine-surfactant foams, gelatine-SDS rheology, gelatine-SDS viscosity

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80 Inhalable Lipid-Coated-Chitosan Nano-Embedded Microdroplets of an Antifungal Drug for Deep Lung Delivery

Authors: Ranjot Kaur, Om P. Katare, Anupama Sharma, Sarah R. Dennison, Kamalinder K. Singh, Bhupinder Singh

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Respiratory microbial infections being among the top leading cause of death worldwide are difficult to treat as the microbes reside deep inside the airways, where only a small fraction of drug can access after traditional oral or parenteral routes. As a result, high doses of drugs are required to maintain drug levels above minimum inhibitory concentrations (MIC) at the infection site, unfortunately leading to severe systemic side-effects. Therefore, delivering antimicrobials directly to the respiratory tract provides an attractive way out in such situations. In this context, current study embarks on the systematic development of lung lia pid-modified chitosan nanoparticles for inhalation of voriconazole. Following the principles of quality by design, the chitosan nanoparticles were prepared by ionic gelation method and further coated with major lung lipid by precipitation method. The factor screening studies were performed by fractional factorial design, followed by optimization of the nanoparticles by Box-Behnken Design. The optimized formulation has a particle size range of 170-180nm, PDI 0.3-0.4, zeta potential 14-17, entrapment efficiency 45-50% and drug loading of 3-5%. The presence of a lipid coating was confirmed by FESEM, FTIR, and X-RD. Furthermore, the nanoparticles were found to be safe upto 40µg/ml on A549 and Calu-3 cell lines. The quantitative and qualitative uptake studies also revealed the uptake of nanoparticles in lung epithelial cells. Moreover, the data from Spraytec and next-generation impactor studies confirmed the deposition of nanoparticles in lower airways. Also, the interaction of nanoparticles with DPPC monolayers signifies its biocompatibility with lungs. Overall, the study describes the methodology and potential of lipid-coated chitosan nanoparticles in futuristic inhalation nanomedicine for the management of pulmonary aspergillosis.

Keywords: dipalmitoylphosphatidylcholine, nebulization, DPPC monolayers, quality-by-design

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79 Synthesis of Highly Stable Multi-Functional Iron Oxide Nanoparticles for Active Mitochondrial Targeting in Immunotherapy

Authors: Masome Moeni, Roya Abedizadeh, Elham Aram, Hamid Sadeghi-Abandansari, Davood Sabour, Robert Menzel, Ali Hassanpour

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Mitochondria- targeting immunogenic cell death inducers (MT-ICD) have been designed to trigger intrinsic apoptosis signalling pathway in malignant cells and revive the antitumour immune system. MT-ICD inducers have considered to be non-specific, which can deteriorate the ability to initiate mitochondria-selective oxidative stress, causing high toxicity. Iron oxide nanoparticles (IONPs) can be an ideal candidate as vehicles for utilizing in immunotherapy due to their biocompatibility, modifiable surface chemistry, magnetic characteristics and multi-functional applications in single platform. These types of NPs can facilitate a real time imaging which can provide an effective strategy to analyse pharmacokinetic parameters of nano-formula, including blood circulation time, targeted and controlled release at tumour microenvironment. To our knowledge, the conjugation of IONPs with MT-ICD and oxaliplatin (a chemotherapeutic agent used for the treatment of colorectal cancer) for immunotherapy have not been investigated. Herein, IONPs were generated via co-precipitation reaction at high temperatures, followed by coating the colloidal suspension with tetraethyl orthosilicate and 3-aminopropyltriethoxysilane to optimize their bio-compatibility, preventing aggregation and maintaining stability at physiological pH, then functionalized with (3-carboxypropyl) triphenyl phosphonium bromide for mitochondrial delivery. Analytical results demonstrated the successful process of IONPs functionalization. In particular, the colloidal particles of doped IONPs exhibited an excellent stability and dispersibility. The resultant particles were also successfully loaded with the oxaliplatin for an active mitochondrial targeting in immunotherapy, resulting in well-maintained super-paramagnetic characteristics and stable structure of the functionalized IONPs with nanoscale particle sizes.

Keywords: Immunotherapy, mitochondria, cancer, iron oxide nanoparticle

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78 Nanoparticles of Hyaluronic Acid for Radiation Induced Lung Damages

Authors: Anna Lierova, Jitka Kasparova, Marcela Jelicova, Lucie Korecka, Zuzana Bilkova, Zuzana Sinkorova

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Hyaluronic acid (HA) is a simple linear, unbranched polysaccharide with a lot of exceptional physiological and chemical properties such as high biocompatibility and biodegradability, strong hydration and viscoelasticity that depend on the size of the molecule. It plays the important role in a variety of molecular events as tissue hydration, mechanical protection of tissues and as well as during inflammation, leukocyte migration, and extracellular matrix remodeling. Also, HA-based biomaterials, including HA scaffolds, hydrogels, thin membranes, matrix grafts or nanoparticles are widely use in various biomedical applications. Our goal is to determine the radioprotective effect of hyaluronic acid nanoparticles (HA NPs). We are investigating effect of ionizing radiation on stability of HA NPs, in vitro relative toxicity of nanoscale as well as effect on cell lines and specific surface receptors and their response to ionizing radiation. An exposure to ionizing radiation (IR) can irreversibly damage various cell types and may thus have implications for the level of the whole tissue. Characteristic manifestations are formation of over-granulated tissue, remodeling of extracellular matrix (ECM) and abortive wound healing. Damages are caused by either direct interaction with DNA and IR proteins or indirectly by radicals formed during radiolysis of water Accumulation and turnover of ECM are a hallmark of radiation induces lung injury, characterized by inflammation, repair or remodeling health pulmonary tissue. HA is a major component of ECM in lung and plays an important role in regulating tissue injury, accelerating tissue repair, and controlling disease outcomes. Due to that, HA NPs were applied to in vivo model (C57Bl/6J mice) before total body or partial thorax irradiation. This part of our research is targeting on effect of exogenous HA on the development and/or mitigating acute radiation syndrome and radiation induced lung injuries.

Keywords: hyaluronic acid, ionizing radiation, nanoparticles, radiation induces lung damages

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77 Finite Element Analysis of Shape Memory Alloy Stents in Coronary Arteries

Authors: Amatulraheem Al-Abassi, K. Khanafer, Ibrahim Deiab

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The coronary artery stent is a promising technology that can treat various coronary diseases. Materials used for manufacturing medical stents should have high biocompatible properties. Stent alloys, in particular, are remarkably promising good clinical outcomes, however, there is threaten of restenosis (reoccurring of artery narrowing due to fatty plaque), stent recoiling, or in long-term the occurrence of stent fracture. However, stents that are made of Nickel-titanium (Nitinol) can bare extensive plastic deformation and resist restenosis. This shape memory alloy has outstanding mechanical properties. Nitinol is a unique shape memory alloy as it has unique mechanical properties such as; biocompatibility, super-elasticity, and recovery to original shape under certain loads. Stent failure may cause complications in vascular diseases and possibly blockage of blood flow. Thus, studying the behaviors of the stent under different medical conditions will help the doctors and cardiologists to predict when it is necessary to change the stent in order to prevent any severe morbidity outcomes. To the best of our knowledge, there are limited published papers that analyze the stent behavior with regards to the contact surfaces of plaque layer and blood vessel. Thus, stent material properties will be discussed in this investigation to highlight the mechanical and clinical differences between various stents. This research analyzes the performance of Nitinol stent in well-known stent design to determine its bearing with stress and its dislocation in blood vessels, in comparison to stents made of different biocompatible materials. In addition, a study of its performance will be represented in the system. Finite Element Analysis is the core of this study. Thus, a physical representative model will be discussed to show the distribution of stress and strain along the interaction surface between the stent and the artery. The reaction of vascular tissue to the stent will be evaluated to predict the possibility of restenosis within the treated area.

Keywords: shape memory alloy, stent, coronary artery, finite element analysis

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76 Modification of Titanium Surfaces with Micro/Nanospheres for Local Antibiotic Release

Authors: Burcu Doymus, Fatma N. Kok, Sakip Onder

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Titanium and titanium-based materials are commonly used to replace or regenerate the injured or lost tissues because of accidents or illnesses. Hospital infections and strong bond formation at the implant-tissue interface are directly affecting the success of the implantation as weak bonding with the native tissue and hospital infections lead to revision surgery. The purpose of the presented study is to modify the surface of the titanium substrates with nano/microspheres for local drug delivery and to prevent hospital infections. Firstly, titanium surfaces were silanized with APTES (3-Triethoxysilylpropylamine) following the negatively charged oxide layer formation. Then characterization studies using Scanning Electron Microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) were done on the modified surfaces. Secondly, microspheres/nanospheres were prepared with chitosan that is a natural polymer and having valuable properties such as non-toxicity, high biocompatibility, low allergen city and biodegradability for biomedical applications. Antibiotic (ciprofloxacin) loaded micro/nanospheres have been fabricated using emulsion cross-linking method and have been immobilized onto the titanium surfaces with different immobilization techniques such as covalent bond and entrapment. Optimization studies on size and drug loading capacities of micro/nanospheres were conducted before the immobilization process. Light microscopy and SEM were used to visualize and measure the size of the produced micro/nanospheres. Loaded and released drug amounts were determined by using UV- spectrophotometer at 278 nm. Finally, SEM analysis and drug release studies on the micro/nanospheres coated Ti surfaces were done. As a conclusion, it was shown that micro/nanospheres were immobilized onto the surfaces successfully and drug release from these surfaces was in a controlled manner. Moreover, the density of the micro/nanospheres after the drug release studies was higher on the surfaces where the entrapment technique was used for immobilization. Acknowledgement: This work is financially supported by The Scientific and Technological Research Council Of Turkey (Project # 217M220)

Keywords: chitosan, controlled drug release, nanosphere, nosocomial infections, titanium

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75 Discrimination of Bio-Analytes by Using Two-Dimensional Nano Sensor Array

Authors: P. Behera, K. K. Singh, D. K. Saini, M. De

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Implementation of 2D materials in the detection of bio analytes is highly advantageous in the field of sensing because of its high surface to volume ratio. We have designed our sensor array with different cationic two-dimensional MoS₂, where surface modification was achieved by cationic thiol ligands with different functionality. Green fluorescent protein (GFP) was chosen as signal transducers for its biocompatibility and anionic nature, which can bind to the cationic MoS₂ surface easily, followed by fluorescence quenching. The addition of bio-analyte to the sensor can decomplex the cationic MoS₂ and GFP conjugates, followed by the regeneration of GFP fluorescence. The fluorescence response pattern belongs to various analytes collected and transformed to linear discriminant analysis (LDA) for classification. At first, 15 different proteins having wide range of molecular weight and isoelectric points were successfully discriminated at 50 nM with detection limit of 1 nM. The sensor system was also executed in biofluids such as serum, where 10 different proteins at 2.5 μM were well separated. After successful discrimination of protein analytes, the sensor array was implemented for bacteria sensing. Six different bacteria were successfully classified at OD = 0.05 with a detection limit corresponding to OD = 0.005. The optimized sensor array was able to classify uropathogens from non-uropathogens in urine medium. Further, the technique was applied for discrimination of bacteria possessing resistance to different types and amounts of drugs. We found out the mechanism of sensing through optical and electrodynamic studies, which indicates the interaction between bacteria with the sensor system was mainly due to electrostatic force of interactions, but the separation of native bacteria from their drug resistant variant was due to Van der Waals forces. There are two ways bacteria can be detected, i.e., through bacterial cells and lysates. The bacterial lysates contain intracellular information and also safe to analysis as it does not contain live cells. Lysates of different drug resistant bacteria were patterned effectively from the native strain. From unknown sample analysis, we found that discrimination of bacterial cells is more sensitive than that of lysates. But the analyst can prefer bacterial lysates over live cells for safer analysis.

Keywords: array-based sensing, drug resistant bacteria, linear discriminant analysis, two-dimensional MoS₂

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74 Enhancing Root Canal Therapy with MTA and Tetracycline-Loaded Nanochitosan: An Approach for Infected Root Canal Treatment in Dogs (in-vivo Animal Study)

Authors: Rania Hanafi Mahmoud Said, Rasha Mohamed Taha

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Background: A recent study has explored the potential of an approach to treating infected root canals using a combination of Mineral Trioxide Aggregate (MTA) and Tetracycline-loaded Nanochitosan. Material and methods: Forty dogs were included in the study, with infected periapical areas induced by leaving access openings in their teeth for four months. Bacteriological samples from the infected root canals were collected and managed anaerobically to identify and count the different microorganisms present. The most common microorganisms detected were Prevotella oris, Fusobacterium nucleatum, Streptococcus viridans, Enterococcus faecalis, Clostridium subterminale, Porphyromonas gingivalis, and Peptostreptococcus anaerobius. The dogs were divided into four groups based on the sealant used to treat the infected periapical areas: Group I: Negative control (no treatment) Group II: Positive control (MTA only) Group III: MTA + tetracycline Group IV: MTA + tetracycline loaded on nanochitosan Results: Periapical areas in Group IV showed significantly more bone healing than those in Groups I, II, and III. The newly formed bone was evaluated radiographically, histologically, and immunohistochemically using Osteopontin (OSP) antibodies. Data collected was statistically analysed using SPSS software at a 0.05 significance level. Conclusion: The study concluded that the combined use of Tetracycline-loaded Nanochitosan and MTA presents a promising approach for the treatment of infected root canals. The potent antimicrobial activity of Tetracycline-loaded Nanochitosan, along with the biocompatibility and desirable properties of MTA, may synergistically contribute to improved clinical outcomes in endodontic therapy. This study has important implications for the clinical management of infected root canals. The combination of Tetracycline-loaded Nanochitosan and MTA could provide a more effective and efficient means of treating these challenging cases. Further research is needed to confirm these findings in humans and to optimize the treatment protocol.

Keywords: mineral trioxide aggregate, tetracycline-loaded nanochitosan, periapical infection, osteopontine

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73 Biocompatible Beta Titanium Alloy Ti36Nb6Ta as a Suitable Material for Bone Regeneration

Authors: Vera Lukasova, Eva Filova, Jana Dankova, Vera Sovkova, Matej Daniel, Michala Rampichova

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Proper bone implants should promote fast adhesion of cells, stimulate cell differentiation and support the formation of bone tissue. Nowadays titanium is used as a biocompatible material capable of bone tissue integration. This study was focused on comparison of bioactive properties of two titanium alloys - beta titanium alloy Ti36Nb6Ta and standard medical titanium alloy Ti6A14V. The advantage of beta titanium alloy Ti36Nb6Ta is mainly that this material does not contain adverse elements like vanadium or aluminium. Titanium alloys were sterilized in ethanol, placed into 48 well plates and seeded with porcine mesenchymal stem cells. Cells were cultivated for 14 days in standard growth cultivation media with osteogenic supplements. Cell metabolic activity was quantified using MTS assay (Promega). Cell adhesion on day 1 and cell proliferation on further days were verified immunohistochemically using beta-actin monoclonal antibody and secondary antibody conjugated with AlexaFluor®488. Differentiation of cells was evaluated using alkaline phosphatase assay. Additionally, gene expression of collagen I was measured by qRT-PCR. Porcine mesenchymal stem cells adhered and spread well on beta titanium alloy Ti36Nb6Ta on day 1. During the 14 days’ time period the cells were spread confluently on the surface of the beta titanium alloy Ti36Nb6Ta. The metabolic activity of cells increased during the whole cultivation period. In comparison to standard medical titanium alloy Ti6A14V, we did not observe any differences. Moreover, the expression of collagen I gene revealed no statistical differences between both titanium alloys. Therefore, a beta titanium alloy Ti36Nb6Ta promotes cell adhesion, metabolic activity, proliferation and collagen I expression equally to standard medical titanium alloy Ti6A14V. Thus, beta titanium is a suitable material that provides sufficient biocompatible properties. This project was supported by the Czech Science Foundation: grant No. 16-14758S.

Keywords: beta titanium alloy, biocompatibility, differentiation, mesenchymal stem cells

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72 Evaluating Antimicrobial Activity of Selenium Nanoparticles Against Food-Borne Bacteria

Authors: Qunying Yuan, Manjula Bomma, Adrian Rhoden, Zhigang Xiao

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Selenium is an essential micronutrient for all mammals and plays an important role in maintaining human physiological functions. The potential applications of selenium as food supplements, cancer-prevention, antimicrobial and anti-inflammatory agents have been investigated in biomedicine and food sciences. Nanoscale of selenium is of particular interest due to its better biocompatibility, higher bioavailability, lower toxicity, more homogeneous distribution, and presumptive controlled release of substances. The objective of this study is to explore whether selenium nanoparticle (SeNP) has the potential to be used as a food preservative to reduce food spoilage. SeNPs were synthesized through ascorbic acid reduction of sodium selenite using the bovine serum albumin (BSA) as capping and stabilizing agent. The chemically synthesized SeNPs had a spherical conformation and a size of 22.8 ± 4.7 nm. FTIR analysis confirmed that the nanoparticles were covered with BSA. We further tested the antimicrobial activity of these SeNPs against common food-borne bacteria. Colony forming unit assay showed that SeNPs exhibited good inhibition on the growth of Listeria Monocytogens (ATCC15313), Staphylococcus epidermidis (ATCC 700583) starting at 0.5µg/mL, but only a moderate inhibitory effect on the growth of Staphylococcus aureus (ATCC12600) and Vibrio alginolyticus (ATCC 33787) at a concentration higher than 10µg/mL and 2.5µg/mL, respectively. There was a mild effect against the growth Salmonella enterica (ATCC19585) when the concentration reached 15µg/mL. No inhibition was observed in the growth of Enterococcus faecalis (ATCC 19433). Surprisingly, SeNPs appeared to promote the growth of Vibrio parahaemolyticus (ATCC43996) and Salmonella enterica (ATCC49284) at 30 µg/mL and above. Our preliminary data suggested that the chemically synthesized SeNPs may be able to inhibit some food-borne bacteria, and SeNP as a food preservative should be used with caution. We will explore the mechanisms of the inhibitory action of chemically synthesized SeNPs on bacterial growth and whether the SeNPs are able to inhibit the development of biofilm and antibiotic resistance.

Keywords: antimicrobial, food-borne bacteria, nanoparticles, selenium

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71 An Investigation of Peptide Functionalized Gold Nanoparticles On Colon Cancer Cells For Biomedical Application

Authors: Rolivhuwa Bishop Ramagoma1*, Lynn Cairncross1, , Saartjie Roux1

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According to the world health organisation, colon cancer is among the most common cancers diagnosed in both men and women. Specifically, it is the second leading cause of cancer related deaths accounting for over 860 000 deaths worldwide in 2018. Currently, chemotherapy has become an essential component of most cancer treatments. Despite progress in cancer drug development over the previous years, traditional chemotherapeutic drugs still have low selectivity for targeting tumour tissues and are frequently constrained by dose-limiting toxicity. The creation of nanoscale delivery vehicles capable of directly directing treatment into cancer cells has recently caught the interest of researchers. Herein, the development of peptide-functionalized polyethylene glycol gold nanoparticles (Peptide-PEG-AuNPs) as a cellular probe and delivery agent is described, with the higher aim to develop a specific diagnostic prototype and assess their specificity not only against cell lines but primary human cells as well. Gold nanoparticles (AuNPs) were synthesized and stabilized through chemical conjugation. The synthesized AuNPs were characterized, stability in physiological solutions was assessed, their cytotoxicity against colon carcinoma and non-carcinoma skin fibroblasts was also studied. Furthermore, genetic effect through real-time polymerase chain reaction (RT-PCR), localization and uptake, peptide specificity were also determined. In this study, different peptide-AuNPs were found to have preferential toxicity at higher concentrations, as revealed by cell viability assays, however, all AuNPs presented immaculate stability for over 3 months following the method of synthesis. The final obtained peptide-PEG-AuNP conjugates showed good biocompatibility in the presence of high ionic solutions and biological media and good cellular uptake. Formulation of colon cancer specific targeting peptide was successful, additionally, the genes/pathways affected by the treatments were determined through RT-PCR. Primary cells study is still on going with promising results thus far.

Keywords: nanotechnology, cancer, diagnosis, therapeutics, gold nanoparticles.

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70 A Facile One Step Modification of Poly(dimethylsiloxane) via Smart Polymers for Biomicrofluidics

Authors: A. Aslihan Gokaltun, Martin L. Yarmush, Ayse Asatekin, O. Berk Usta

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Poly(dimethylsiloxane) (PDMS) is one of the most widely used materials in the fabrication of microfluidic devices. It is easily patterned and can replicate features down to nanometers. Its flexibility, gas permeability that allows oxygenation, and low cost also drive its wide adoption. However, a major drawback of PDMS is its hydrophobicity and fast hydrophobic recovery after surface hydrophilization. This results in significant non-specific adsorption of proteins as well as small hydrophobic molecules such as therapeutic drugs limiting the utility of PDMS in biomedical microfluidic circuitry. While silicon, glass, and thermoplastics have been used, they come with problems of their own such as rigidity, high cost, and special tooling needs, which limit their use to a smaller user base. Many strategies to alleviate these common problems with PDMS are lack of general practical applicability, or have limited shelf lives in terms of the modifications they achieve. This restricts large scale implementation and adoption by industrial and research communities. Accordingly, we aim to tailor biocompatible PDMS surfaces by developing a simple and one step bulk modification approach with novel smart materials to reduce non-specific molecular adsorption and to stabilize long-term cell analysis with PDMS substrates. Smart polymers that blended with PDMS during device manufacture, spontaneously segregate to surfaces when in contact with aqueous solutions and create a < 1 nm layer that reduces non-specific adsorption of organic and biomolecules. Our methods are fully compatible with existing PDMS device manufacture protocols without any additional processing steps. We have demonstrated that our modified PDMS microfluidic system is effective at blocking the adsorption of proteins while retaining the viability of primary rat hepatocytes and preserving the biocompatibility, oxygen permeability, and transparency of the material. We expect this work will enable the development of fouling-resistant biomedical materials from microfluidics to hospital surfaces and tubing.

Keywords: cell culture, microfluidics, non-specific protein adsorption, PDMS, smart polymers

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69 Oligoalkylamine Modified Poly(Amidoamine) Generation 4.5 Dendrimer for the Delivery of Small Interfering RNA

Authors: Endris Yibru Hanurry, Wei-Hsin Hsu, Hsieh-Chih Tsai

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In recent years, the discovery of small interfering RNAs (siRNAs) has got great attention for the treatment of cancer and other diseases. However, the therapeutic efficacy of siRNAs has been faced with many drawbacks because of short half-life in blood circulation, poor membrane penetration, weak endosomal escape and inadequate release into the cytosol. To overcome these drawbacks, we designed a non-viral vector by conjugating polyamidoamine generation 4.5 dendrimer (PDG4.5) with diethylenetriamine (DETA)- and tetraethylenepentamine (TEPA) followed by binding with siRNA to form polyplexes through electrostatic interaction. The result of 1H nuclear magnetic resonance (NMR), 13C NMR, correlation spectroscopy, heteronuclear single–quantum correlation spectroscopy, and Fourier transform infrared spectroscopy confirmed the successful conjugation of DETA and TEPA with PDG4.5. Then, the size, surface charge, morphology, binding ability, stability, release assay, toxicity and cellular internalization were analyzed to explore the physicochemical and biological properties of PDG4.5-DETA and PDG4.5-TEPA polyplexes at specific N/P ratios. The polyplexes (N/P = 8) exhibited spherical nanosized (125 and 85 nm) particles with optimum surface charge (13 and 26 mV), showed strong siRNA binding ability, protected the siRNA against enzyme digestion and accepted biocompatibility to the HeLa cells. Qualitatively, the fluorescence microscopy image revealed the delocalization (Manders’ coefficient 0.63 and 0.53 for PDG4.5-DETA and PDG4.5-TEPA, respectively) of polyplexes and the translocation of the siRNA throughout the cytosol to show a decent cellular internalization and intracellular biodistribution of polyplexes in HeLa cells. Quantitatively, the flow cytometry result indicated that a significant (P < 0.05) amount of siRNA was internalized by cells treated with PDG4.5-DETA (68.5%) and PDG4.5-TEPA (73%) polyplexes. Generally, PDG4.5-DETA and PDG4.5-TEPA were ideal nanocarriers of siRNA in vitro and might be used as promising candidates for in vivo study and future pharmaceutical applications.

Keywords: non-viral carrier, oligoalkylamine, poly(amidoamine) dendrimer, polyplexes, siRNA

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68 Effect of Curing Temperature on the Textural and Rheological of Gelatine-SDS Hydrogels

Authors: Virginia Martin Torrejon, Binjie Wu

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Gelatine is a protein biopolymer obtained from the partial hydrolysis of animal tissues which contain collagen, the primary structural component in connective tissue. Gelatine hydrogels have attracted considerable research in recent years as an alternative to synthetic materials due to their outstanding gelling properties, biocompatibility and compostability. Surfactants, such as sodium dodecyl sulfate (SDS), are often used in hydrogels solutions as surface modifiers or solubility enhancers, and their incorporation can influence the hydrogel’s viscoelastic properties and, in turn, its processing and applications. Literature usually focuses on studying the impact of formulation parameters (e.g., gelatine content, gelatine strength, additives incorporation) on gelatine hydrogels properties, but processing parameters, such as curing temperature, are commonly overlooked. For example, some authors have reported a decrease in gel strength at lower curing temperatures, but there is a lack of research on systematic viscoelastic characterisation of high strength gelatine and gelatine-SDS systems at a wide range of curing temperatures. This knowledge is essential to meet and adjust the technological requirements for different applications (e.g., viscosity, setting time, gel strength or melting/gelling temperature). This work investigated the effect of curing temperature (10, 15, 20, 23 and 25 and 30°C) on the elastic modulus (G’) and melting temperature of high strength gelatine-SDS hydrogels, at 10 wt% and 20 wt% gelatine contents, by small-amplitude oscillatory shear rheology coupled with Fourier Transform Infrared Spectroscopy. It also correlates the gel strength obtained by rheological measurements with the gel strength measured by texture analysis. Gelatine and gelatine-SDS hydrogels’ rheological behaviour strongly depended on the curing temperature, and its gel strength and melting temperature can be slightly modified to adjust it to given processing and applications needs. Lower curing temperatures led to gelatine and gelatine-SDS hydrogels with considerably higher storage modulus. However, their melting temperature was lower than those gels cured at higher temperatures and lower gel strength. This effect was more considerable at longer timescales. This behaviour is attributed to the development of thermal-resistant structures in the lower strength gels cured at higher temperatures.

Keywords: gelatine gelation kinetics, gelatine-SDS interactions, gelatine-surfactant hydrogels, melting and gelling temperature of gelatine gels, rheology of gelatine hydrogels

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67 Nanoparticles Made of Amino Acid Derived Biodegradable Polymers as Promising Drug Delivery Containers

Authors: Sophio Kobauri, Tengiz Kantaria, Temur Kantaria, David Tugushi, Nina Kulikova, Ramaz Katsarava

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Polymeric disperse systems such as nanoparticles (NPs) are of high interest for numerous applications in contemporary medicine and nanobiotechnology to a considerable potential for treatment of many human diseases. The important technological advantages of NPs usage as drug carriers (nanocontainers) are their high stability, high carrier capacity, feasibility of encapsulation of both hydrophilic or hydrophobic substances, as well as a high variety of possible administration routes, including oral application and inhalation. NPs can also be designed to allow controlled (sustained) drug release from the matrix. These properties of NPs enable improvement of drug bioavailability and might allow drug dosage decrease. The targeted and controlled administration of drugs using NPs might also help to overcome drug resistance, which is one of the major obstacles in the control of epidemics. Various degradable and non-degradable polymers of both natural and synthetic origin have been used for NPs construction. One of the most promising for the design of NPs are amino acid-based biodegradable polymers (AABBPs) which can clear from the body after the fulfillment of their function. The AABBPs are composed of naturally occurring and non-toxic building blocks such as α-amino acids, fatty diols and dicarboxylic acids. The particles designed from these polymers are expected to have an improved bioavailability along with a high biocompatibility. The present work deals with a systematic study of the preparation of NPs by cost-effective polymer deposition/solvent displacement method using AABBPs. The influence of the nature and concentration of surfactants, concentration of organic phase (polymer solution), and the ratio organic phase/inorganic(water) phase, as well as of some other factors on the size of the fabricated NPs have been studied. It was established that depending on the used conditions the NPs size could be tuned within 40-330 nm. At the next step of this research was carried out an evaluation of biocompability and bioavailability of the synthesized NPs using a stable human cell culture line – A549. It was established that the obtained NPs are not only biocompatible but they stimulate the cell growth.

Keywords: amino acids, biodegradable polymers, bioavailability, nanoparticles

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66 In vitro Study of Laser Diode Radiation Effect on the Photo-Damage of MCF-7 and MCF-10A Cell Clusters

Authors: A. Dashti, M. Eskandari, L. Farahmand, P. Parvin, A. Jafargholi

Abstract:

Breast Cancer is one of the most considerable diseases in the United States and other countries and is the second leading cause of death in women. Common breast cancer treatments would lead to adverse side effects such as loss of hair, nausea, and weakness. These complications arise because these cancer treatments damage some healthy cells while eliminating the cancer cells. In an effort to address these complications, laser radiation was utilized and tested as a targeted cancer treatment for breast cancer. In this regard, tissue engineering approaches are being employed by using an electrospun scaffold in order to facilitate the growth of breast cancer cells. Polycaprolacton (PCL) was used as a material for scaffold fabricating because of its biocompatibility, biodegradability, and supporting cell growth. The specific breast cancer cells have the ability to create a three-dimensional cell cluster due to the spontaneous accumulation of cells in the porosity of the scaffold under some specific conditions. Therefore, we are looking for a higher density of porosity and larger pore size. Fibers showed uniform diameter distribution and final scaffold had optimum characteristics with approximately 40% porosity. The images were taken by SEM and the density and the size of the porosity were determined with the Image. After scaffold preparation, it has cross-linked by glutaraldehyde. Then, it has been washed with glycine and phosphate buffer saline (PBS), in order to neutralize the residual glutaraldehyde. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromidefor (MTT) results have represented approximately 91.13% viability of the scaffolds for cancer cells. In order to create a cluster, Michigan Cancer Foundation-7 (MCF-7, breast cancer cell line) and Michigan Cancer Foundation-10A (MCF-10A, human mammary epithelial cell line) cells were cultured on the scaffold in 24 well plate for five days. Then, we have exposed the cluster to the laser diode 808 nm radiation to investigate the effect of laser on the tumor with different power and time. Under the same conditions, cancer cells lost their viability more than the healthy ones. In conclusion, laser therapy is a viable method to destroy the target cells and has a minimum effect on the healthy tissues and cells and it can improve the other method of cancer treatments limitations.

Keywords: breast cancer, electrospun scaffold, polycaprolacton, laser diode, cancer treatment

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65 Reactions of 4-Aryl-1H-1,2,3-Triazoles with Cycloalkenones and Epoxides: Synthesis of 2,4- and 1,4-Disubstituted 1,2,3-Triazoles

Authors: Ujjawal Kumar Bhagat, Kamaluddin, Rama Krishna Peddinti

Abstract:

The Huisgen’s 1,3-dipolar [3+2] cycloaddition of organic azides and alkynes often give the mixtures of both the regioisomers 1,4- and 1,5- disubstituted 1,2,3-triazoles. Later, in presence of metal salts (click chemistry) such as copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) was used for the synthesis of 1,4-disubstituted 1,2,3-triazoles as a sole products regioselectively. Also, the ‘click reactions’ of Ruthenium-catalyzed azides-alkynes cycloaddition (RuAAC) is used for the synthesis of 1,5-disubstituted 1,2,3-triazoles as a single isomer. The synthesis of 1,4- and 1.5-disubstituted 1,2,3-triazoles has become the gold standard of ‘click chemistry’ due to its reliability, specificity, and biocompatibility. The 1,4- and 1,5-disubstituted 1,2,3-triazoles have emerged as one of the most powerful entities in the varieties of biological properties like antibacterial, antitubercular, antitumor, antifungal and antiprotozoal activities. Some of the 1,4,5-trisubstituted 1,2,3-triazoles exhibit Hsp90 inhibiting properties. The 1,4-disubstituted 1,2,3-triazoles also play a big role in the area of material sciences. The triazole-derived oligomeric, polymeric structures are the potential materials for the preparation of organic optoelectronics, silicon elastomers and unimolecular block copolymers. By the virtue of hydrogen bonding and dipole interactions, the 1,2,3-triazole moiety readily associates with the biological targets. Since, the 4-aryl-1H-1,2,3-triazoles are stable entities, they are chemically robust and very less reactive. In this regard, the addition of 4-aryl-1H-1,2,3-triazoles as nucleophiles to α,β-unsaturated carbonyls and nucleophilic substitution with the epoxides constitutes a powerful and challenging synthetic approach for the generation of disubstituted 1,2,3-triazoles. Herein, we have developed aza-Michael addition of 4-aryl-1H-1,2,3-triazoles to 2-cycloalken-1-ones in the presence of an organic base (DABCO) in acetonotrile solvent leading to the formation of disubstituted 1,2,3-triazoles. The reaction provides 1,4-disubstituted triazoles, 3-(4-aryl-1H-1,2,3-triazol-1-yl)cycloalkanones in major amount along with 1,5-disubstituted 1,2,3-triazoles, minor regioisomers with excellent combined chemical yields (upto99%). The nucleophilic behavior of 4-aryl-1H-1,2,3-triazoles was also tested in the ring opening of meso-epoxides in the presence of organic bases (DABCO/Et3N) in acetonotrile solvent furnishing the two regioisomers1,4- and 1,5-disubstituted 1,2,3-triazoles. Thus, the novelty of this methodology is synthesis of diversified disubstituted 1,2,3-triazoles under metal free condition.The results will be presented in detail.

Keywords: aza-Michael addition, cycloalkenones, epoxides, triazoles

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64 Chemical, Structural and Mechanical Optimization of Zr-Based Bulk Metallic Glass for Biomedical Applications

Authors: Eliott Guérin, Remi Daudin, Georges Kalepsi, Alexis Lenain, Sebastien Gravier, Benoit Ter-Ovanessian, Damien Fabregue, Jean-Jacques Blandin

Abstract:

Due to interesting compromise between mechanical and corrosion properties, Zr-based BMGs are attractive for biomedical applications. However, the enhancement of their glass forming ability (GFA) is often achieved by addition of toxic elements like Ni or Be, which is of course a problem for such applications. Consequently, the development of Ni-free Be-free Zr-based BMGs is of great interest. We have developed a Zr-based (Ni and Be-free) amorphous metallic alloy with an elastic limit twice the one of Ti-6Al-4V. The Zr56Co28Al16 composition exhibits a yield strength close to 2 GPa and low Young’s modulus (close to 90 GPa) [1-2]. In this work, we investigated Niobium (Nb) addition through substitution of Zr up to 8 at%. Cobalt substitution has already been reported [3], but we chose Zr substitution to preserve the glass forming ability. In this case, we show that the glass forming ability for 5 mm diameters rods is maintained up to 3 at% of Nb substitution using suction casting in cooper moulds. Concerning the thermal stability, we measure a strong compositional dependence on the glass transition (Tg). Using DSC analysis (heating rate 20 K/min), we show that the Tg rises from 752 K for 0 at% of Nb to 759 K for 3 at% of Nb. Yet, the thermal range between Tg and the crystallisation temperature (Tx) remains almost unchanged from 33 K to 35 K. Uniaxial compression tests on 2 mm diameter pillars and 3 points bending (3PB) tests on 1 mm thick plates are performed to study the Nb addition on the mechanical properties and the plastic behaviour. With these tests, an optimal Nb concentration is found, improving both plasticity and fatigue resistance. Through interpretations of DSC measurements, an attempt is made to correlate the modifications of the mechanical properties with the structural changes. The optimized chemical, structural and mechanical properties through Nb addition are encouraging to develop the potential of this BMG alloy for biomedical applications. For this purpose, we performed polarisation, immersion and cytotoxicity tests. The figure illustrates the polarisation response of Zr56Co28Al16, Zr54Co28Al16Nb2 and TA6V as a reference after 2h of open circuit potential. The results show that the substitution of Zr by a small amount of Nb significantly improves the corrosion resistance of the alloy.

Keywords: metallic glasses, amorphous metal, medical, mechanical resistance, biocompatibility

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63 Two-Component Biocompartible Material for Reconstruction of Articular Hyaline Cartilage

Authors: Alena O. Stepanova, Vera S. Chernonosova, Tatyana S. Godovikova, Konstantin A. Bulatov, Andrey Y. Patrushev, Pavel P. Laktionov

Abstract:

Trauma and arthrosis, not to mention cartilage destruction in overweight and elders put hyaline cartilage lesion among the most frequent diseases of locomotor system. These problems combined with low regeneration potential of the cartilage make regeneration of articular cartilage a high-priority task of tissue engineering. Many types of matrices, the procedures of their installation and autologous chondrocyte implantation protocols were offered, but certain aspects including adhesion of the implant with surrounding cartilage/bone, prevention of the ossification and fibrosis were not resolved. Simplification and acceleration of the procedures resulting in restoration of normal cartilage are also required. We have demonstrated that human chondroblasts can be successfully cultivated at the surface of electrospun scaffolds and produce extracellular matrix components in contrast to chondroblasts grown in homogeneous hydrogels. To restore cartilage we offer to use stacks of electrospun scaffolds fixed with photopolymerized solution of prepared from gelatin and chondroitin-4-sulfate both modified by glycidyl methacrylate and non-toxic photoinitator Darocur 2959. Scaffolds were prepared from nylon 6, polylactide-co-glicolide and their mixtures with modified gelatin. Illumination of chondroblasts in photopolymerized solution using 365 nm LED light had no effect on cell viability at compressive strength of the gel less than0,12 MPa. Stacks of electrospun scaffolds provide good compressive strength and have the potential for substitution with cartilage when biodegradable scaffolds are used. Vascularization can be prevented by introduction of biostable scaffolds in the layers contacting the subchondral bone. Studies of two-component materials (2-3 sheets of electrospun scaffold) implanted in the knee-joints of rabbits and fixed by photopolymerization demonstrated good crush resistance, biocompatibility and good adhesion of the implant with surrounding cartilage. Histological examination of the implants 3 month after implantation demonstrates absence of any inflammation and signs of replacement of the biodegradable scaffolds with normal cartilage. The possibility of intraoperative population of the implants with autologous cells is being investigated.

Keywords: chondroblasts, electrospun scaffolds, hyaline cartilage, photopolymerized gel

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62 Propolis as Antioxidant Formulated in Nanoemulsion

Authors: Rachmat Mauludin, Irda Fidrianny, Dita Sasri Primaviri, Okti Alifiana

Abstract:

Natural products such as propolis, green tea and corncob are containing several compounds called antioxidant. Antioxidant can be used in topical application to protect skin against free radical, prevent skin cancer and skin aging. Previous study showed that the extract of propolis that has the highest antioxidant activity was ethanolic extract of propolis (EEP). It is important to make a dosage form that could keep the stability and could protect the effectiveness of antioxidant activity of the extracts. In this research, nanoemulsion (NE) was chosen to formulate those natural products. NE is a dispersion system between oil phase and water phase that formed by mechanical force with a lot amount of surfactants and has globule size below 100 nm. In pharmaceutical industries, NE was preferable for its stability, biodegradability, biocompatibility, its ease to be absorbed and eliminated, and for its use as carrier for lipophilic drugs. First, all of the natural products were extracted using reflux methods. Green tea and corncob were extracted using 96% ethanol while propolis using 70% ethanol. Then, the extracts were concentrated using rotavapor to obtain viscous extracts. The yield of EEP was 11.12%; green tea extract (GTE) was 23.37%; and corncob extract (CCE) was 17.23%. EEP contained steroid/triterpenoid, flavonoid and saponin. GTE contained flavonoid, tannin, and quinone while CCE contained flavonoid, phenol and tannin. The antioxidant activities of the extracts were then measured using DPPH scavenging capacity methods. The values of DPPH scavenging capacity were 61.14% for EEP; 97.16% for GTE; and 78.28% for CCE. The value of IC50 for EEP was 0.41629 ppm. After the extracts were evaluated, NE was prepared. Several surfactants and co-surfactants were used in many combinations and ratios in order to form a NE. Tween 80 and Kolliphor RH40 were used as surfactants while glycerin and propylene glycol were used as co-surfactants. The best NE consists of 26.25% of Kolliphor RH40; 8.75% of glycerin; 5% of rice bran oil; 3% of extracts; and 57% of water. EEP NE had globule size around 23.72 nm; polydispersity index below 0.5; and did not cause any irritation on rabbits. EEP NE was proven to be stable after passing stability test within 63 days at room temperature and 6 cycles of Freeze and Thaw test without separated. Based on TEM (Transmission Electron Microscopy) test, EEP NE had spherical structure with most of its size below 50 nm. The antioxidant activity of EEP NE was monitored for 6 weeks and showed no significant difference. The value of DPPH scavenging capacity for EEP NE was around 58%; for GTE NE was 96.75%; and for CCE NE was 55.69%.

Keywords: propolis, green tea, corncob, antioxidant, nanoemulsion

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61 Polymeric Sustained Biodegradable Patch Formulation for Wound Healing

Authors: Abhay Asthana, Gyati Shilakari Asthana

Abstract:

It’s the patient compliance and stability in combination with controlled drug delivery and biocompatibility that forms the core feature in present research and development of sustained biodegradable patch formulation intended for wound healing. The aim was to impart sustained degradation, sterile formulation, significant folding endurance, elasticity, biodegradability, bio-acceptability and strength. The optimized formulation was developed using component including polymers including Hydroxypropyl methyl cellulose, Ethylcellulose, and Gelatin, and Citric Acid PEG Citric acid (CPEGC) triblock dendrimers and active Curcumin. Polymeric mixture dissolved in geometric order in suitable medium through continuous stirring under ambient conditions. With continued stirring Curcumin was added with aid of DCM and Methanol in optimized ratio to get homogenous dispersion. The dispersion was sonicated with optimum frequency and for given time and later casted to form a patch form. All steps were carried out under under strict aseptic conditions. The formulations obtained in the acceptable working range were decided based on thickness, uniformity of drug content, smooth texture and flexibility and brittleness. The patch kept on stability using butter paper in sterile pack displayed folding endurance in range of 20 to 23 times without any evidence of crack in an optimized formulation at room temperature (RT) (24 ± 2°C). The patch displayed acceptable parameters after stability study conducted in refrigerated conditions (8±0.2°C) and at RT (24 ± 2°C) upto 90 days. Further, no significant changes were observed in critical parameters such as elasticity, biodegradability, drug release and drug content during stability study conducted at RT 24±2°C for 45 and 90 days. The drug content was in range 95 to 102%, moisture content didn’t exceeded 19.2% and patch passed the content uniformity test. Percentage cumulative drug release was found to be 80% in 12h and matched the biodegradation rate as drug release with correlation factor R2>0.9. The biodegradable patch based formulation developed shows promising results in terms of stability and release profiles.

Keywords: sustained biodegradation, wound healing, polymers, stability

Procedia PDF Downloads 309
60 Nanoparticles-Protein Hybrid-Based Magnetic Liposome

Authors: Amlan Kumar Das, Avinash Marwal, Vikram Pareek

Abstract:

Liposome plays an important role in medical and pharmaceutical science as e.g. nano scale drug carriers. Liposomes are vesicles of varying size consisting of a spherical lipid bilayer and an aqueous inner compartment. Magnet-driven liposome used for the targeted delivery of drugs to organs and tissues1. These liposome preparations contain encapsulated drug components and finely dispersed magnetic particles. Liposomes are vesicles of varying size consisting of a spherical lipid bilayer and an aqueous inner compartment that are generated in vitro. These are useful in terms of biocompatibility, biodegradability, and low toxicity, and can control biodistribution by changing the size, lipid composition, and physical characteristics2. Furthermore, liposomes can entrap both hydrophobic and hydrophilic drugs and are able to continuously release the entrapped substrate, thus being useful drug carriers. Magnetic liposomes (MLs) are phospholipid vesicles that encapsulate magneticor paramagnetic nanoparticles. They are applied as contrast agents for magnetic resonance imaging (MRI)3. The biological synthesis of nanoparticles using plant extracts plays an important role in the field of nanotechnology4. Green-synthesized magnetite nanoparticles-protein hybrid has been produced by treating Iron (III)/Iron(II) chloride with the leaf extract of Dhatura Inoxia. The phytochemicals present in the leaf extracts act as a reducing as well stabilizing agents preventing agglomeration, which include flavonoids, phenolic compounds, cardiac glycosides, proteins and sugars. The magnetite nanoparticles-protein hybrid has been trapped inside the aqueous core of the liposome prepared by reversed phase evaporation (REV) method using oleic and linoleic acid which has been shown to be driven under magnetic field confirming the formation magnetic liposome (ML). Chemical characterization of stealth magnetic liposome has been performed by breaking the liposome and release of magnetic nanoparticles. The presence iron has been confirmed by colour complex formation with KSCN and UV-Vis study using spectrophotometer Cary 60, Agilent. This magnet driven liposome using nanoparticles-protein hybrid can be a smart vesicles for the targeted drug delivery.

Keywords: nanoparticles-protein hybrid, magnetic liposome, medical, pharmaceutical science

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