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Popa A.C.,National Institute of Materials Physics Bucharest | Popa A.C.,Army Center for Medical Research | Stan G.E.,National Institute of Materials Physics Bucharest | Husanu M.A.,National Institute of Materials Physics Bucharest | And 4 more authors.
International Journal of Nanomedicine | Year: 2017

Synthetic physiological fluids are currently used as a first in vitro bioactivity assessment for bone grafts. Our understanding about the interactions taking place at the fluid-implant interface has evolved remarkably during the last decade, and does not comply with the traditional International Organization for Standardization/final draft International Standard 23317 protocol in purely inorganic simulated body fluid. The advances in our knowledge point to the need of a true paradigm shift toward testing physiological fluids with enhanced biomimicry and a better understanding of the materials’ structure-dissolution behavior. This will contribute to "upgrade" our vision of entire cascades of events taking place at the implant surfaces upon immersion in the testing media or after implantation. Starting from an osteoinductive bioglass composition with the ability to alleviate the oxidative stress, thin bioglass films with different degrees of polymerization were deposited onto titanium substrates. Their biomineralization activity in simulated body fluid and in a series of new inorganic-organic media with increasing biomimicry that more closely simulated the human intercellular environment was compared. A comprehensive range of advanced characterization tools (scanning electron microscopy; grazing-incidence X-ray diffraction; Fourier-transform infrared, micro-Raman, energy-dispersive, X-ray photoelectron, and surface-enhanced laser desorption/ionization time-of-flight mass spectroscopies; and cytocompatibility assays using mesenchymal stem cells) were used. The information gathered is very useful to biologists, biophysicists, clinicians, and material scientists with special interest in teaching and research. By combining all the analyses, we propose herein a step forward toward establishing an improved unified protocol for testing the bioactivity of implant materials. © 2017 Popa et al.

Florescu A.,Titu Maiorescu University | Efrem I.C.,University of Medicine and Pharmacy of Craiova | Haidoiu C.,Army Center for Medical Research | Hertzog R.,Army Center for Medical Research | Biclesanu F.C.,Titu Maiorescu University
Romanian Journal of Morphology and Embryology | Year: 2014

Study objectives: In vitro evaluation and comparison of the adhesion of a generation-7 adhesive system to normal and sclerotic dentin. Materials and Methods: For this study, sound teeth as well as teeth with sclerotic dentin, which had been extracted for periodontal reasons, were prepared. Class 5 cavities were prepared, then restored by means of the SE 1-step Futurabond M (Voco) adhesive system, as well as the Estelite Sigma Quick (Tokuyama Dental) composite resin. For teeth with sclerotic dentin, the hypermineralized superficial layer was removed by means of round bur on low speed, then the adhesive system and composite resin were applied. These teeth were prepared for microscopic study according to the protocol specific to each microscope. For the study involving the confocal microscope, the adhesive was mixed with the Evans Blue dye before being applied to the tooth, then the same protocol was followed. Results: When applied to normal dentin, Futurabond M (Voco), the generation-7 adhesive system, forms a hybrid layer with a depth of 20-25 μm, while it can be noted that it pervades 6-8 μm into the dentinal tubules. When applied to sclerotic dentin, it was noted that the adhesive system does not pervade into the tubules, with an approximately 10-15 μm depth of the hybrid layer. Conclusions: The adhesion to sclerotic dentin shows particular aspects. When it is desired to employ generation-7 adhesive systems (SE 1-step) on sclerotic dentin, the therapeutic approach needs to include the following supplementary stages: removal of the superficial hypermineralized layer, as well as predemineralization with 37% phosphoric acid; they are the only stages that might improve the adhesion to this substrate. © 2014, Editura Academiei Romane, All rights reserved.

PubMed | Army Center for Medical Research, Carol Davila University of Medicine and Pharmacy, University of Medicine and Pharmacy of Craiova and Polytechnic University of Bucharest
Type: Journal Article | Journal: Current health sciences journal | Year: 2014

Nimesulide is a weakly acidic non-steroidal anti-inflammatory drug (NSAIDs). Like many non-steroidal anti-inflammatory drugs, Nimesulide is very sparingly soluble in water ( 0.01 mg/mL).The poor aqueous solubility and wettability of Nimesulide gives rise to difficulties in pharmaceutical formulations for oral or parenteral delivery, which may lead to variable bioavailability. Based on the Biopharmaceutical Classification System (BCS), Nimesulide is considered a BCS 2 drug (poorly soluble and highly permeable). Solubilization in surfactant solutions above critical micelle concentration (CMC) offers one approach to the formulation of poorly soluble drugs. Weakly acidic and basic drugs may be brought into solution by the solubilizing action of surfactants. In this study, different concentrations of Tween 80 was used in combination with buffer (pH 7.4) to increase the solubility of Nimesulide. The results show that the dependence of the released amount on the Tween concentration is not linear, very low Tween concentration showing a decrease of solubility, probably connected to a critical micelle concentration at the interface Nimesulide solution. An analytical artefact connected to a decreasing ultraviolet absorption of Nimesulide because of Nimesulide precipitation, the formation of a colloidal solution is possible, and the phenomenon remains to be searched further. It is hard to explain that for an almost complete solubilization a significant Tween quantity is necessary and this should be more than that of other slightly soluble drugs.

Duta L.,Romanian National Institute for Lasers, Plasma and Radiation Physics | Popa A.C.,Army Center for Medical Research | Popa A.C.,Carol Davila University of Medicine and Pharmacy | Popa A.C.,National Institute of Materials Physics Bucharest | And 2 more authors.
Romanian Reports in Physics | Year: 2014

We report on the synthesis by PLD of bioactive glass (BG) films onto ultra high molecular weight polyethylene acetabular cups, and their preliminarily characterization after immersion in simulated body fluid. Fourier Transform Infrared spectra evidenced the strong depolymerization of the BG coatings. Scanning Electron Microscopy evidenced that the typical PLD film surface was converted after soaking in SBF to a rough one consisting of acicular crystals. Energy Dispersive Spectroscopy analysis demonstrated a remarkable conservation of the targets stoichiometry. The functionalization of acetabular cups with BG films by PLD should allow for the fabrication of implant coatings with improved osteoinductive characteristics. © 2014 Romanian Reports in Physics. All rights reserved.

Stan G.E.,National Institute of Materials Physics Bucharest | Popa A.C.,National Institute of Materials Physics Bucharest | Popa A.C.,Army Center for Medical Research | Popa A.C.,Carol Davila University of Medicine and Pharmacy | And 3 more authors.
Applied Surface Science | Year: 2013

Bioglasses (BG) are the inorganic materials exhibiting the highest indices of bioactivity. Their appliance as films for bio-functionalization of metallic implant surfaces has been regarded as an optimal solution for surpassing their limited bulk mechanical properties. This study reports on magnetron sputtering of alkali-free BG thin films by varying the target-to-substrate working distance, which proved to play an important role in determining the films' properties. Post deposition heat-treatments at temperatures slightly above the glass transformation temperature were then applied to induce inter-diffusion processes at the BG/titanium substrate interface and strengthening the bonding as determined by pull-out adherence measurements. The morphological and structural features assessed by SEM-EDS, XRD, and FTIR revealed a good correlation between the formations of inter-metallic titanium silicide phases and the films' bonding strength. The highest mean value of pull-out adherence (60.3 ± 4.6 MPa), which is adequate even for load-bearing biomedical applications, was recorded for films deposited at a working distance of 35 mm followed by a heat-treatment at 750°C for 2 h in air. The experimental findings are explained on the basis of structural, compositional and thermodynamic considerations. ©2013 Elsevier B.V. All rights reserved.

PubMed | Army Center for Medical Research, Victor Babes National Institute of Pathology, University of Aveiro, Turin Polytechnic University in Tashkent and National Institute of Materials Physics Bucharest
Type: | Journal: Journal of the mechanical behavior of biomedical materials | Year: 2015

Bioactive glasses are currently considered the suitable candidates to stir the quest for a new generation of osseous implants with superior biological/functional performance. In congruence with this vision, this contribution aims to introduce a reliable technological recipe for coating fairly complex 3D-shaped implants (e.g. dental screws) with uniform and mechanical resistant bioactive glass films by the radio-frequency magnetron sputtering method. The mechanical reliability of the bioactive glass films applied to real Ti dental implant fixtures has been evaluated by a procedure comprised of cold implantation in pig mandibular bone from a dead animal, followed by immediate tension-free extraction tests. The effects of the complex mechanical strains occurring during implantation were analysed by scanning electron microscopy coupled with electron dispersive spectroscopy. Extensive biocompatibility assays (MTS, immunofluorescence, Western blot) revealed that the bioactive glass films stimulated strong cellular adhesion and proliferation of human dental pulp stem cells, without promoting their differentiation. The ability of the implant coatings to conserve a healthy stem cell pool is promising to further endorse the fabrication of new osseointegration implant designs with extended lifetime.

Borisova S.,Carol Davila University of Medicine and Pharmacy | Mormenschi D.,Carol Davila University of Medicine and Pharmacy | Sarbu I.,Carol Davila University of Medicine and Pharmacy | Mircioiu C.,Carol Davila University of Medicine and Pharmacy | Mircioiu C.,Army Center for Medical Research
Therapeutics, Pharmacology and Clinical Toxicology | Year: 2012

Tests of erythrocyte sedimentation provide a measure of the acute phase response to inflammatorydiseases, most infections, in cancer, cardiovascular and many other diseases. The term erythrocyte sedimentationrate (ESR) is retained because of traditional usage, although a single measurement after 60 minutes isnot a rate Recommendations of International Council for Standardization in Haematology (ICSH) considersESR as defined by the height of sedimented column of erythrocytes at a given time (usually one hour).Single parameter characterization of sedimentation of erythrocytes by ESR represents a course approach ofcomplex phenomena. The simplicity of the sedimentation rate is only apparent. In practice, a lot of difficultiesarises in definition of the "rate" since its estimation requires at least two points on the sedimentationcurve. If the sedimentation does not start immediately, a positive lag-time appearing, ESR measured valueat one hour is a rate lower than the real slope, estimated from sedimentation curve. If sedimentation is morerapid and curve reach saturation by sedimentation curve is greater thanthe rate defined by official ESR. A more in depth analysis of data started in the paper from "sedimentationcurves" which characterise dynamic evolution in time of phenomena. Comparison of curves arises greatdifficulties even for mathematicians. Metrics in the spaces of curves implies a more advanced mathematics.Consequently, sedimentation curves where replaced by some of their global parameters such as initial slopeor area under curve. Further for comparison of curves were introduced some specific methods from cancerresearch, biopharmacy and pharmacokinetics. It concerns the rate of sedimentation this was estimated fromthe initial slope of the curves. In fact the curve could be modelled for a longer time interval using a twophaselinear regression. The slope of the first line could define better the ESR. If we consider evolutionof height of sediment as a "survival curve", the Kaplan Meyer method becomes immediately applicable.From dissolution studies in biopharmacy the official metric on the release curves space, based on the sum ofsquared differences between matched points of the sedimentation curves. A set of methods (linear regressionin estimation of the slopes, of the similarity of curves using f2 metrics, of time-lag, of half-time etc.), aswell as comparison of Areas Under Sedimentation Curves, were applied in evaluation of clopidogrels effectat concentrations between 1 and 8 mg/ml. © 2012.

Stan G.E.,National Institute of Materials Physics Bucharest | Marcov D.A.,National Institute of Materials Physics Bucharest | Popa A.C.,Army Center for Medical Research | Popa A.C.,Carol Davila University of Medicine and Pharmacy | Husanu M.A.,National Institute of Materials Physics Bucharest
Digest Journal of Nanomaterials and Biostructures | Year: 2010

Hydrogenated amorphous carbon (a-C:H) films were grown by radio-frequency (1.78 MHz) plasma enhanced chemical vapour deposition technique onto medical grade Ti6Al4V substrates. By varying the deposition pressure (13.33 Pa and 53.33 Pa, respectively) and methane dilution (20% and 60%, respectively) several types of carbonic films were obtained, presenting different bonding structures, surface energies and morphological features reflected in their biological behaviour. FTIR, Raman, UV-Vis, XPS and AFM measurements were used for characterizing these structures. The surface energy was determined by contact angle measurements, and their thrombogenicity was tested by the activated partial thromboplastin time (aPTT) method. We have noticed that at the same values of methane in argon dilution but at different pressure values, the film structure was totally changed: soft polymer-like carbon (PLC) type at the higher pressure and hard diamond-like carbon (DLC) type at the lower pressure. Raman spectroscopy and XPS suggested that the highest sp 3 ratio (~ 52%), was found for DLC films prepared in a 60% methane dilution in argon. It has been found that for both PLC and DLC structures the surface energy has a decreasing tendency with the methane concentration increase in the deposition atmosphere. Excellent aPTT results were obtained for the DLC-60 (18.6±0.3 min) and PLC-20 (17.4±0.5 min) structures, superior to those recorded for Ti6Al4V and PMMA commercial materials. These values recommend the prepared carbonic structures for medical applications: harder coatings (DLC) for metal prostheses (heart valves, acetabular cups etc.), while softer and flexible coatings (PLC) for the textile vessels or stents biofunctionalization.

Stan G.E.,National Institute of Materials Physics Bucharest | Popa A.C.,Army Center for Medical Research | Popa A.C.,Carol Davila University of Medicine and Pharmacy | Bojin D.,Polytechnic University of Bucharest
Digest Journal of Nanomaterials and Biostructures | Year: 2010

In this study, Fourier Transform Infrared Spectroscopy (FTIR) in Attenuated Total Reflectance mode was employed as main characterization technique to investigate the reaction mechanisms in vitro (SBF) of bioglass and glass-ceramic sputtered coatings. Two bioglass compositional systems are compared in order to gain more information regarding their in vitro bioreactivity. Important correlations between the concentration of non-bridging silicon-oxygen (Si-O-NBO) groups and the content of network modifiers were found. FTIR revealed that the high concentrations of Si-O-NBO groups are promoting the enhancing of coatings' reactivity. This information could be very useful for the development and tailoring of new bioactive glasses with an optimum biological behaviour. By varying the compositional features and the structural state, the sputtered glassy coatings exhibited different in vitro behaviour: inertness, resorbability and bioactivity.

PubMed | Army Center for Medical Research
Type: Journal Article | Journal: Toxicology letters | Year: 2013

Chemical warfare agents, such as soman, and pesticides, such as chlorpyrifos, dichlorvos or malathion, are toxic organophosphorous compounds (OPCs) that are readily absorbed by the skin. Decontamination using solvents or surfactants may modify the cornified layer - the skins main barrier against xenobiotic penetration. Thus, effective skin decontamination with fewer side effects is desired. We determined the membrane absorption, decontamination and desorption of toxic OPCs using human skin and synthetic membrane (cuprophane, cellulose acetate, methyl ethyl cellulose, acetophane and nylon) models, and estimated the efficacy of adsorptive powders (bentonite and magnesium trisilicate) at inhibiting this transfer. Using validated flow-through and static diffusion cell and HPLC methods, we found that the transfer of OPCs depends on their membrane affinity. The chlorpyrifos transfer decreased with a decrease in the membrane hydrophilicity, and that of malathion across hydrophilic membranes was less than half of that across hydrophobic membranes. We reliably modeled the toxicant transfer through the skin and synthetic membranes as first-order kinetic and/or square root law transfer processes, suggesting a potential application of synthetic membranes for predicting percutaneous absorption of OPCs. All tested adsorptive powders, applied either alone or as mixtures, significantly reduced the toxicant amount transferred across all membrane models, suggesting a potential therapeutic application with fewer later undesired effects on intact skin.

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