Potential Use In Biomedical Applications Research Articles

Biosafety Evaluation of Nanoparticles in View of Genotoxicity and Carcinogenicity Studies: A Systematic Review

Nanoparticles (NPs) are used in various forms in consumer products including, cosmetics, food packaging, textiles and also in air and water cleaning, production of electro chromic windows, or smart windows and gas sensors. Many NPs have also been evaluated for potential use in biomedical applications as efficient delivery carriers for cancer diagnosis and therapy. Nowadays, NPs are being developed to create fascinating nanotechnology products. To develop NPs for broad applications, potential risks to human health and the environment should be evaluated and taken into consideration. Again, to translate these nanomaterials to the clinic and industrial domains, their biosafety needs to be verified, particularly in terms of genotoxic and carcinogenic effects. To evaluate evidenced-based practices for NPs safety, we performed a systematic review of the published English-language literature. We performed a systematic keyword search of PubMed for original research articles pertaining to reports on assessment of risks due to carcinogenic and mutagenic effects by different NPs. We identified 362 original articles available for analysis. The included studies were published between 1993 and 2012. The in vivo or in vitro genotoxicity studies were performed on only 18 out of 148 kinds of NPs in industry today. Likewise, the carcinogenicity investigations were performed on only 14 out of 148 NPs. The 10 types of the NPs including some titanium, aluminium, carbon black and silver molecules were found to have both mutagenic and carcinogenic potential. The important finding was also that there is a lack of systematic assessment of the DNA damaging and carcinogenic potential of NPs in spite of their extensive use in nanotechnological applications.

Synthesis and characterization of graphene-based nanocomposites with potential use for biomedical applications

In the present study, graphene-based nanocomposites containing different amounts of nanofiller dispersed into Bis-GMA/tetraethyleneglycol diacrylate (Bis-GMA/TEGDA) polymer matrix have been prepared. In particular, the graphene dispersions, produced at high concentration (up to 6 mg/ml) by simple sonication of graphite in TEGDA monomer, have been used for the direct preparation of nanocomposite copolymers with Bis-GMA. The morphology of the obtained nanocomposites has been investigated as well as their thermal and mechanical properties. SEM analyses have clearly shown that graphene deeply interacts with the polymer matrix, thus resulting in a reinforcing effect on the material as proved by compression and hardness tests; at variance, graphene does not seem to affect the glass transition temperature of the obtained polymer networks.

PEG-coated folic acid-modified superparamagnetic MnFe2O4 nanoparticles for hyperthermia therapy and drug delivery

Superparamagnetic iron oxide-based nanoparticles (SPIONS) have attracted an enormous attention for their potential use in biomedical applications due to their good biocompatibility and low toxicity. Current study is about doxorubicin-loaded multifunctional MnFe2O4 nanoparticles surface-modified with polyethylene glycol (PEG) & folic acid (FA) for multimodal cancer therapy. Infrared spectroscopy and thermogravimetric data confirmed this surface modification. Nanoparticles were of moderate colloidal dispersion due to PEG coating. Composite nanoparticles having mean diameter of about 22 nm were of core–shell structure having about 31% (wt) organic shell over the (remaining) magnetic core. MnFe2O4 core of about 16 nm was superparamagnetic due to the pseudo-single domain structure. Drug loading & releasing were efficient in the initial 8 h and gradual in later hours. Magnetic heating was studied by exposing the magnetic fluid to high frequency magnetic field. Temperature of the fluid rose to 45 °C from 25 °C in about 22 min, which is an effective and appropriate temperature for the localized hyperthermia treatment of cancer.

Synthesis and characterization of poly(4-vinyl pyridine-co-styrene)/FHAP nanocomposite, and its biomedical application

Among the composite materials, ceramic/polymer possesses significant advantages of high mechanical reliability and excellent biocompatibility for applications in load-bearing areas. In this work, PVPCS(Poly (4-vinyl pyridine-co-styrene))/FHAp nanocomposites of varying weight percentages were synthesized and characterized physical-chemically by XRD, FTIR, 31P NMR, TGA, DTA, and FE-SEM and biologically by antimicrobial and anti-inflammatory assays for evaluating their potential use for biomedical applications. The results indicated that the size and crystallinity of FHAp nanoparticles decrease with increase in PVPCS concentration in the composite. SEM confirmed the presence of FHAp nano rod crystals in PVPCS matrix. The nano PVPCS20/FHAp demonstrated the highest antifungal and antibacterial activity and favorable inhibition of human cell hemolysis. The designed PVPCS/FHAp nanocomposites constitute promising candidates for biomedical applications.

Shape‐Memory Biopolymers Based on β‐Sheet Structures of Polyalanine Segments Inspired by Spider Silks

The molecular structural design learned from natural materials enables synthetic polymers with desirable and unique features to be fabricated. Inspired by spider silks, short-chain polyalanine (PA) is introduced into multiblock biopolymers with poly(ε-caprolactone) segments via a coupling reaction. As a result, PA segments in biopolymers form similar β-sheet crystals to that of natural spidroins. These new biopolymers are found to exhibit nearly complete shape recovery and high shape fixity, along with significantly improved thermal stability due to the strong β-sheet structures as netpoints. This work provides new insight for the design of novel shape-memory polymers with potential use in biomedical applications.

An in vitro assessment of the interaction of cadmium selenide quantum dots with DNA, iron, and blood platelets

Cadmium selenide (CdSe) quantum dots have gained increased attention for their potential use in biomedical applications. This has raised interest in assessing their toxicity. In this study, water-soluble, cysteine-capped CdSe nanocrystals with an average size of 15 nm were prepared through a one-pot solution-based method. The CdSe nanoparticles were synthesized in batches in which the concentration of the capping agent was varied with the aim of stabilizing the quantum dot core. The effects of the CdSe quantum dots on DNA stability, aggregation of blood platelets, and reducing activity of iron were evaluated in vitro . DNA damage was observed at a concentration of 200 μg/mL of CdSe quantum dots. Furthermore, the CdSe nanocrystals exhibited high reducing power and chelating activity, suggesting that they may impair the function of haemoglobin by interacting with iron. In addition, the CdSe quantum dots promoted aggregation of blood platelets in a dose dependent manner.

Semicrystalline Dihydroxyacetone Copolymers Derived from Glycerol

The ring-opening polymerization of glycerol-derived six-membered cyclic dimethylacetal dihydroxyacetone carbonate (MeO2DHAC) have been studied both in solution and bulk conditions with organic catalysts. The guanidine 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) was the most active catalyst in solution, whereas the thiourea/sparteine catalytic system displayed the most predictable kinetics. Ring-opening polymerization of MeO2DHAC or copolymerization with ε-caprolactone (CL) in the melt occurred readily with TBD as catalyst to afford random copolymers. Acetal deprotection afforded the polycarbonate poly(dihydroxyactone carbonate) (p(DHAC)) or poly(carbonate ester) copolymers p(DHAC-r-CL). The polycarbonate p(DHAC) is a high-melting thermoplastic with a melting point of 246 °C. The p(DHAC-r-CL) copolymers all displayed semicrystalline behavior as evidenced by DSC and WAXS analysis with Tg and Tm changing as a function of comonomer composition. These new materials could have potential use in biomedical applications or as biomass-derived thermoplastics.

Microstructure, mechanical property, corrosion behavior, and in vitro biocompatibility of Zr–Mo alloys

In this study, the microstructure, mechanical properties, corrosion behaviors, and in vitro biocompatibility of Zr-Mo alloys as a function of Mo content after solution treatment were systemically investigated to assess their potential use in biomedical application. The experimental results indicated that Zr-1Mo alloy mainly consisted of an acicular structure of α' phase, while ω phase formed in Zr-3Mo alloy. In Zr-5Mo alloy, retained β phase and a small amount of precipitated α phase were observed. Only the retained β phase was obtained in Zr-10Mo alloy. Zr-1Mo alloy exhibited the greatest hardness, bending strength, and modulus among all experimental Zr-Mo alloys, while β phase Zr-10Mo alloy had a low modulus. The results of electrochemical corrosion indicated that adding Mo into Zr improved its corrosion resistance which resulted in increasing the thermodynamic stability and passivity of zirconium. The cytotoxicity test suggested that the extracts of the studied Zr-Mo alloys produced no significant deleterious effect to fibroblast cells (L-929) and osteoblast cells (MG 63), indicating an excellent in vitro biocompatibility. Based on these facts, certain Zr-Mo alloys potentially suitable for different biomedical applications were proposed.

Fiber average size and distribution dependence on the electrospinning parameters of poly(vinylidene fluoride–trifluoroethylene) membranes for biomedical applications

Poly(vinylidene fluoride–trifluoroethylene), P(VDF–TrFE), electrospun membranes were obtained from a mixture of dimethylformamide (DMF) and methylethylketone (MEK) solvents. The inclusion of MEK to the solvent system promotes a faster solvent evaporation allowing complete polymer crystallization in the jet traveling between the tip and the grounded collector. The main electrospinning processing parameters were systematically changed to study their influence on fiber dimensions and distribution. Applied voltage and inner needle diameter do not have a large influence on the electrospun fiber average diameter but do on the fiber diameter distribution. On the other hand, increasing the distance between the needle tip and the collector gives origin to fibers with larger average diameter. Independently of the processing conditions, all membranes are produced in the electroactive phase of the polymer. Further, MC-3T3-E1 cell adhesion is not inhibited by the fiber membrane preparation, showing their potential use for biomedical applications.

Synthesis and preliminary characterization of polyethylene glycol (PEG)/hydroxyapatite (HAp) nanocomposite for biomedical applications

Currently, composite materials have gained momentum in the field of orthopedics and maxillofacial surgery. Among the composite materials, ceramic/polymer possesses significant advantages of high mechanical reliability and excellent biocompatibility for applications in load bearing areas. In this work, polyethylene glycol (PEG)/hydroxyapatite (HAp) nanocomposites of varying weight percentages were synthesized and characterized physical-chemically by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), 31P nuclear magnetic resonance (NMR), thermo gravimetric analysis (TGA), differential thermal analysis (DTA) and field emission-scanning electron microscopy (FE-SEM) and biologically by antimicrobial and anti-inflammatory assays to evaluate their potential use for biomedical applications. The results indicated that the size and crystallinity of HAp nanoparticles decrease with increase in PEG concentration in the composite. SEM confirmed the presence of HAp nanorod crystals in PEG matrix. The nano PEG-20/HAp demonstrated the highest antifungal and antibacterial activity and favorable inhibition of human cell hemolysis. The designed PEG/HAp nanocomposites constitute promising candidates for biomedical applications. Key words: Hydroxyapatite, nanocrystalline, nanocomposite, poly ethylene glycol.

Magnetic, optical and relaxometric properties of organically coated gold–magnetite (Au–Fe3O4) hybrid nanoparticles for potential use in biomedical applications

We present the magnetic, optical and relaxometric properties of multifunctional Au–Fe3O4 hybrid nanoparticles (HNPs), as possible novel contrast agents (CAs) for magnetic resonance imaging (MRI). The HNPs have been synthesized by wet chemical methods in heterodimer and core–shell geometries and capped with oleylamine. Structural characterization of the samples have been made by X-ray diffraction and transmission electron microscopy, while magnetic properties have been investigated by means of Superconducting Quantum Interference Device-SQUID magnetometry experiments. As required for MRI applications using negative CAs, the samples resulted superparamagnetic at room temperature and well above their blocking temperatures. Optical properties have been investigated by analyzing the optical absorbtion spectra collected in UV–visible region. Relaxometric measurements have been performed on organic suspensions of HNPs and Nuclear Magnetic Resonance (NMR) dispersion curves have been obtained by measuring the longitudinal 1/T1 and transverse 1/T2 relaxation rates of solvent protons in the range 10kHz/300MHz at room temperature. NMR relaxivities r1 and r2 have been compared with ENDOREM®, one of the commercial superparamagnetic iron oxide based MRI contrast agents. MRI contrast enhancement efficiencies have been investigated also by examining T2-weighted MR images of suspensions. The experimental results suggest that the nanoparticles' suspensions are good candidates as negative CAs.

Microstructures and mechanical properties of as cast Mg–Zr–Ca alloys for biomedical applications

The microstructures and mechanical properties of as cast Mg–Zr–Ca alloys were investigated for potential use in biomedical applications. The Mg–Zr–Ca alloys were fabricated by commercial pure Mg (99·9 mass-%), Ca (99·9 mass-%) and master Mg–33 mass-%Zr alloy. The microstructures of the alloys were examined by X-ray diffraction analysis and optical microscopy, and the mechanical properties were determined from tensile tests. The experimental results indicate that the Mg–Zr–Ca alloys with 1 mass-%Ca are composed of one single α phase; these alloys with 2 mass-%Ca consist of both Mg2Ca and α phase, and all the alloys exhibit typical coarse microstructures. An increase in Zr increases the strength of Mg–Zr–Ca alloys with 1 mass-%Ca, and the formation of Mg2Ca decreases the strength of the alloys. Mg–1Zr–1Ca alloy (mass-%) has the highest strength and best ductility among all the studied alloys.

전기분무에 의한 생분해성 폴리포스파젠 마이크로입자의 제조

Biodegradable poly[(glycine ethyl ester)-(phenylalanine ethyl ester) phosphazene](PGPP) microparticles were fabricated by electrohydrodynamic atomization to apply drug release test. Atomization parameters such as applied voltage, polymer concentration, and molecular weight were investigated to inspect their effects on the size and morphology of microparticles. The average diameter of PGPP microparticles decreased as increasing applied voltage and solution flow rate. Dichloromethane/ dioxane mixture shows better results for the preparation of microparticles than single solvent owing to the different PGPP solubility in solvent. Blending PGPP polymers with proper molecular weights not only favored the production of spherical PGPP microparticles via electrohydrodynamic atomization, but also provided a way to adjust drug (rifampicin) release behavior. Drug-loaded biodegradable polyphosphazene microspheres can be fabricated via electrohydrodynamic atomization, which has potential use in biomedical applications.

RECENT DEVELOPMENT FOR SYNTHESIS OF MAGNETIC NANOPARTICLES FOR BIOMEDICAL APPLICATIONS

An update is presented on some recent syntheses of magnetic nanoparticles developed in our group for potential use in biomedical applications. Particular attention is paid to (i) the preparation of magnetic nanoparticles that are readily dispersed in aqueous solution (ii) the synthesis of alloy magnetic nanoparticles and (iii) novel synthesis methods used to control the physical properties of the nanoparticles.

Microstructural Characterization and Mechanical Properties of Mg-Zr-Ca Alloys Prepared by Hot-Extrusion for Biomedical Applications

This paper investigated the microstructural characterization and mechanical properties of Mg-Zr-Ca alloys prepared by hot-extrusion for potential use in biomedical applications. Mg-Zr-Ca alloys were fabricated by commercial pure Mg (99.9%), Ca (99.9%), and master Mg-33% Zr alloy (mass%). The microstructural characterization of the hot-extruded Mg-Zr-Ca alloys was examined by X-ray diffraction analysis and optical microscopy, and the mechanical properties were determined from tensile tests. The experimental results indicate that the hot-extruded Mg-Zr-Ca alloys with 1 mass% Ca are composed of one single phase and those alloys with 2 mass% Ca consist of both Mg2Ca and α phase. The hot-extruded Mg-Zr-Ca alloys exhibit equiaxed granular microstructures and the hot-extrusion process can effectively increase both the tensile strength and ductility of Mg-Zr-Ca alloys. The hot-extruded Mg-1Zr-1Ca alloy (mass%) exhibits the highest strength and best ductility among all the alloys, and has much higher strength than the human bone, suggesting that it has a great potential to be a good candidate for biomedical application.

Microstructures and mechanical properties of Ti–Mo alloys cold-rolled and heat treated

In this study, the microstructures and mechanical properties of Ti–10Mo and Ti–20Mo alloys (mass%) are investigated to assess the potential use in biomedical applications. The microstructures are examined by X-ray diffraction analysis (XRD) and scanning electron microscopy (SEM). The mechanical properties are determined from uniaxial tensile tests. The experimental results indicate that the microstructures and mechanical properties of Ti–Mo alloys are dependent upon the cold rolling, solution heat treatment, and Mo content. The Ti–10Mo alloy exhibits (α″ + β) and (β + ω) phases under the cold rolling (CR) and solution treatment (ST), respectively. By contrast, the Ti–20Mo alloy comprises only β phase under such conditions. The quenched Ti–20Mo alloy has the lowest elastic modulus and CR Ti–20Mo alloy has the highest tensile strength. The quenched Ti–10Mo alloy exhibits the excellent ductility and two-stage yielding from stress-strain curves due to the stress-induced martensite transformation from β to α″ during tensile deformation. These Ti–Mo alloys exhibit low yield strength and good ductility, and they are more suitable for biomedical applications than the conventional metallic biomaterials from the viewpoint of better mechanical compatibility. The quenched Ti–10Mo alloy has some advantages over the other β binary Ti–Mo alloys for biomedical applications. β type Ti–Mo–Sn alloys are expected to be promising candidates for novel metallic biomaterials. ► The microstructures and mechanical properties of Ti–Mo alloys are dependent upon the cold rolling, solution heat treatment, and Mo content. ► The quenched Ti–10Mo alloy exhibits the excellent ductility and two-stage yielding due to stress-induced martensite transformation from beta to alpha double prime during tensile deformation. ► The Ti–Mo alloys are more suitable for biomedical applications than the conventional metallic biomaterials from the viewpoint of better mechanical compatibility. ► The quenched Ti–10Mo alloy has more advantages over the other beta binary Ti–Mo alloys for biomedical applications.

Synthesis and characterization of monodisperse, mesoporous, and magnetic sub-micron particles doped with a near-infrared fluorescent dye

Recently, multifunctional silica nanoparticles have been investigated extensively for their potential use in biomedical applications. We have prepared sub-micron monodisperse and stable multifunctional mesoporous silica particles with a high level of magnetization and fluorescence in the near infrared region using an one-pot synthesis technique. Commercial magnetite nanocrystals and a conjugated-NIR-dye were incorporated inside the particles during the silica condensation reaction. The particles were then coated with polyethyleneglycol to stop aggregation. X-ray diffraction, N 2 adsorption analysis, TEM, fluorescence and absorbance measurements were used to structurally characterize the particles. These mesoporous silica spheres have a large surface area (1978 m 2/g) with 3.40 nm pore diameter and a high fluorescence in the near infrared region at λ=700 nm. To explore the potential of these particles for drug delivery applications, the pore accessibility to hydrophobic drugs was simulated by successfully trapping a hydrophobic ruthenium dye complex inside the particle with an estimated concentration of 3 wt%. Fluorescence imaging confirmed the presence of both NIR dye and the post-grafted ruthenium dye complex inside the particles. These particles moved at approximately 150 μm/s under the influence of a magnetic field, hence demonstrating the multifunctionality and potential for biomedical applications in targeting and imaging.

Effects of Increasing Carbon Nanofiber Density in Polyurethane Composites for Inhibiting Bladder Cancer Cell Functions

Polyurethane (PU) is a versatile elastomer that is commonly used in biomedical applications. In turn, materials derived from nanotechnology, specifically carbon nanofibers (CNFs), have received increasing attention for their potential use in biomedical applications. Recent studies have shown that the dispersion of CNFs in PU significantly enhances composite nanoscale surface roughness, tensile properties, and thermal stability. Although there have been studies concerning normal primary cell functions on such nanocomposites, there have been few studies detailing cancer cell responses. Since many patients who require bladder transplants have suffered from bladder cancer, the ideal bladder prosthetic material should not only promote normal primary human urothelial cell (HUC) function, but also inhibit the return of bladder cancerous cell activity. This study examined the correlation between transitional (UMUC) and squamous (or SCaBER) urothelial carcinoma cells and HUC on PU:CNF nanocomposites of varying PU and CNF weight ratios (from pure PU to 4:1 [PU:CNF volume ratios], 2:1, 1:1, 1:2, and 1:4 composites to pure CNF). Composites were characterized for mechanical properties, wettability, surface roughness, and chemical composition by atomic force microscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, and goniometry. The adhesion and proliferation of UMUC and SCaBER cancer cells were assessed by MTS assays. Cellular responses were further quantified by measuring the amounts of nuclear mitotic protein 22 (NMP-22), vascular endothelial growth factor (VEGF), and tumor necrosis factor alpha. Results demonstrated that both UMUC and SCaBER cell proliferation rates decreased over time on substrates with increased CNF in PU. In addition, with the exception of VEGF from UMUC (which was the same across all materials), composites containing the most CNF activated cancer cells (UMUC and SCaBER) the least, as shown by their decreased expression of NMP-22, tumor necrosis factor alpha, and VEGF. Moreover, the adhesion of HUC increased on composites containing more CNF than PU. Overall levels of NMP-22 were significantly lower in HUC than in cancerous UMUC and SCaBER cells on PU:CNF composites. Thus, this study provided a novel nanocomposite consisting of CNF and PU that should be further studied for inhibiting the return of cancerous bladder tissue and for promoting normal non-cancerous bladder tissue formation.

Plasma treatment of polycaprolactone at medium pressure

Polycaprolactone (PCL) is a biodegradable and biocompatible polymer which has acquired much attention the last few years for its potential use in biomedical applications, like tissue engineering and bone repair. Due to its hydrophobic nature, cell adhesion, proliferation and differentiation are however far less than optimal. To overcome this drawback, the surface properties of PCL need to be improved. In this work, a medium pressure dielectric barrier discharge (DBD) operating in different atmospheres (dry air, argon and helium) is employed to alter the surface properties of PCL. Chemical changes on the plasma-treated surfaces are examined using contact angle measurements and XPS analysis. Results show that discharge gas can have a significant influence on the chemical composition of the PCL surfaces: air and argon plasmas introduce oxygen-containing groups, while helium plasmas incorporate both oxygen and nitrogen-containing functionalities. This latter observation can however be explained by the fact that the helium discharge operates in the glow mode.

Bubbly Cavitating Flow Generation and Investigation of Its Erosional Nature for Biomedical Applications

This paper presents a study that investigates the destructive energy output resulting from hydrodynamic bubbly cavitation in microchannels and its potential use in biomedical applications. The research performed in this study includes results from bubbly cavitation experiments and findings showing the destructive effects of bubbly cavitating flow on selected solid specimens and live cells. The bubbles generated by hydrodynamic cavitation are highly destructive at the surfaces of the target medium on which they are carefully focused. The resulting destructive energy output could be effectively used for biomedical treatments, such as destroying kidney stones (renal calculi) or killing cancer cells. Motivated by this potential, the cavitation damage to cancerous cells and material removal from chalk pieces (which possess similar material properties as some kidney stones) was investigated. Our results showed that cavitation could induce damage both on chalk pieces and leukemia/lymphoma cells. We discovered that hydrodynamic cavitation exposure had early and delayed effects on cancer cell survival. Hence, the potential of hydrodynamic bubbly cavitation generated at the microscale for biomedical treatments was revealed using the microchannel configuration as a microorifice (with an inner diameter of 147 μm and a length of 1.52 cm), which acts as the source of bubbly cavitating flows.