A structure-activity approach towards the toxicity assessment of multicomponent metal oxide nanomaterials.

The increase of human and environmental exposure to engineered nanomaterials (ENMs) due to the emergence of nanotechnology has raised concerns over their safety. The challenging nature of in vivo and in vitro toxicity assessment methods for ENMs, has led to emerging in silico techniques for ENM toxicity assessment, such as structure-activity relationship (SAR) models. Although such approaches have been extensively developed for the case of single-component nanomaterials, the case of multicomponent nanomaterials (MCNMs) has not been thoroughly addressed. In this paper, we present a SAR approach for the case metal and metal oxide MCNMs. The developed SAR framework is built using a dataset of 796 individual toxicity measurements for 340 different MCNMs, towards human cells, mammalian cells, and bacteria. The novelty of the approach lies in the multicomponent nature of the nanomaterials, as well as the size, diversity and heterogeneous nature of the dataset used. Furthermore, the approach used to calculate descriptors for surface loaded MCNMs, and the mechanistic insight provided by the model results can assist the understanding of MCNM toxicity. The developed models are able to correctly predict the toxic class of the MCNMs in the heterogeneous dataset, towards a wide range of human cells, mammalian cells and bacteria. Using the abovementioned approach, the principal toxicity pathways and mechanisms are identified, allowing a more holistic understanding of metal oxide MCNM toxicity.

Additive manufacturing of hydroxyapatite-chitosan-genipin composite scaffolds for bone tissue engineering applications.

Additive manufacturing holds promise for the fabrication of three-dimensional scaffolds with precise geometry, to serve as substrates for the guided regeneration of natural tissue. In this work, a bioinspired approach is adopted for the synthesis of hybrid hydroxyapatite hydrogels, which were subsequently printed to form 3D scaffolds for bone tissue engineering applications. These hydrogels consist of hydroxyapatite nanocrystals, biomimetically synthesized in the presence of both chitosan and l-arginine. To improve their mechanical properties, chemical crosslinking was performed using a natural crosslinking agent (genipin), and their rheology was modified by employing an acetic acid/gelatin solution. Regarding the 3D printing process, several parameters (flow, infill and perimeter speed) were studied in order to accurately produce scaffolds with predesigned geometry and micro-architecture, while also applying low printing temperature (15 °C). Following the printing procedure, the 3D scaffolds were freeze dried in order to remove the entrapped solvents and therefore, obtain a porous interconnected network. Evaluation of porosity was performed using micro-computed tomography and nanomechanical properties were assessed through nanoindentation. Results of both characterization techniques, showed that the scaffolds' porosity as well as their modulus values, fall within the corresponding range of the respective values of cancellous bone. The biocompatibility of the 3D printed scaffolds was assessed using MG63 human osteosarcoma cells for 7 days of culturing. Cell viability was evaluated by MTT assay as well as double staining and visualized under fluorescence microscopy, while cell morphology was analyzed through scanning electron microscopy. Biocompatibility tests, revealed that the scaffolds constitute a cell-friendly environment, allowed them to adhere on the scaffolds' surface, increase their population and maintain high levels of viability.

In vitro cytotoxicity assessment of pristine and carboxyl-functionalized MWCNTs.

The wide use of carbon nanotubes (CNTs) in consumer products, i.e. composites, coatings, food packaging, etc, raise concerns about the adverse effects that CNTs can induce in humans and environment. Yet, there is no global consensus regarding risks that CNTs may pose, while controversial evidence exists also on the toxic effects associated with chemical surface modification, a prerequisite for their incorporation in different matrices. Moreover, there is limited information available about the underlying mechanisms, especially when cells' interactions with the nanomaterial is assessed by imaging techniques. The present study aims at evaluating the in vitro cytotoxicity of pristine and oxygen functionalized multi-walled CNTs (MWCNTs) by assessing cell viability and apoptosis in combination with scanning electron microscopy (SEM) observations of stabilised cells. Direct observation of adenocarcinoma human epithelial cells (A549) was performed after incubation with 12.5, 50 and 100 µg/ml MWCNTs, for 0.5, 1 and 3 h, simulating a real exposure scenario during an accident, taking into account industrial safety issues during the production and use of the nanomaterial. Functionalized MWCNTs induced higher time- and dose-dependent toxic effects as compared to pristine. The SEM observations revealed the damaging effect on the cell membrane, offering insights about the toxic mechanism that takes place.

Nanostructuring the surface of dual responsive hollow polymer microspheres for versatile utilization in nanomedicine-related applications.

The design and fabrication of hollow polymer microspheres responsive to various stimuli comprises a promising approach for the development of multifunctional and efficient systems for various nanomedicine-related applications. In this paper, we present the preparation of poly(methacrylic acid-co-N,N'-methylenebis(acrylamide)-co-poly(ethylene glycol) methyl ether methacrylate-co-N,N'-bis(acryloyl)cystamine) (PMAA(S-S)) hollow microspheres following a two-stage distillation precipitation polymerization procedure. Magnetic and silver nanocrystals were chemically grown on the surface of the hollow polymer microspheres, resulting in a composite system with interesting properties. We evaluated the performance of the composite hollow microspheres as magnetic hyperthermia mediators and their surface-enhanced Raman spectroscopy activity. Assessment of Daunorubicin-loaded PMAA(S-S) hollow microspheres performance as effective drug carriers was carried out through drug release experiments upon application of different pH and reducing conditions. pH and redox responsiveness as well as basic mechanisms of release profiles are discussed. Furthermore, in vitro cytotoxicity of empty and drug-loaded PMAA(S-S) hollow microspheres against MCF-7 cancer cells was investigated in order to evaluate their performance as drug carriers.

Microspheres as therapeutic delivery agents: synthesis and biological evaluation of pH responsiveness.

A soft template method was used for the synthesis of pH-responsive microcontainers with an inner cavity. Poly(glycidyl methacrylate) (PGMA) microspheres of narrow size distribution were synthesized by soap-free radical emulsion polymerization and the coating of the microspheres was carried out by the same procedure. The procedure consists of two steps. In the first step the sacrificial template is synthesized and in the second step the shell is formed. Acrylic acid was used as a coating monomer, with the aim of introducing pH sensitivity in the synthesized microcontainers. A loading and release study of the anthracycline drug doxorubicin (DOX) was also carried out. The toxicity evaluation of the drug was carried out using the MTT assay, and the necrotic effect was studied using trypan blue.

Nanomechanical and nanotribological properties of plasma nanotextured superhydrophilic and superhydrophobic polymeric surfaces.

Oxygen plasma-induced surface modification of polymethylmethacrylate (PMMA), under plasma conditions favouring (maximizing) roughness formation, has been shown to create textured surfaces of roughness size and morphology dependent on the plasma-treatment time and subsequent morphology stabilization procedure. Superhydrophobic or superhydrophilic surfaces can thus be obtained, with potential applications in antireflective self-cleaning surfaces, microfluidics, wetting-dewetting control, anti-icing etc, necessitating determination of their mechanical properties. In this study, nanoindentation is used to determine the reduced modulus and hardness of the surface, while nanoscratch tests are performed to measure the coefficient of friction. The data are combined to assess the wear behaviour of such surfaces as a first guide for their practical applications. Short-time plasma treatment slightly changes mechanical, tribological and wear properties compared to untreated PMMA. However, a significant decrease in the reduced modulus and hardness and an increase in the coefficient of friction are observed after long plasma-treatment times. The C(4)F(8) plasma deposited thin hydrophobic layer on the polymeric surfaces (untreated and treated) reveals good adhesion, while its mechanical properties are greatly influenced by the substrate; it is also found that it effectively protects the polymeric surfaces, reducing plastic deformation.

The size effect of crystalline inclusions on the fracture modes in glass-ceramic materials.

The main parameters influencing the mechanical performance of glass-ceramic materials are the shape and mean size of the ceramic phase, i.e. the crystalline inclusions. The aim of the present work is twofold: first, to study the effect of the above parameters on the modes of fracture in two kinds of glass-ceramic materials by the use of the static microindentation technique; second, to interpret the experimental results by the application of a simple physical model. It was found that reduction in the size of granularly shaped crystallite inclusions or reduction of the width of needle-like crystalline inclusions results in an increase of the extent of crack propagation, while the fracture mode shifts from intergranular to transgranular. These observations were successfully interpreted in terms of energetic arguments related to the size of the crystalline inclusions with respect to the width of a disordered zone acting as an interface between them and the amorphous matrix.