A data reusability assessment in the nanosafety domain based on the NSDRA framework followed by an exploratory quantitative structure activity relationships (QSAR) modeling targeting cellular viability.

INTRODUCTION: The current effort towards the digital transformation across multiple scientific domains requires data that is Findable, Accessible, Interoperable and Reusable (FAIR). In addition to the FAIR data, what is required for the application of computational tools, such as Quantitative Structure Activity Relationships (QSARs), is a sufficient data volume and the ability to merge sources into homogeneous digital assets. In the nanosafety domain there is a lack of FAIR available metadata. METHODOLOGY: To address this challenge, we utilized 34 datasets from the nanosafety domain by exploiting the NanoSafety Data Reusability Assessment (NSDRA) framework, which allowed the annotation and assessment of dataset's reusability. From the framework's application results, eight datasets targeting the same endpoint (i.e. numerical cellular viability) were selected, processed and merged to test several hypothesis including universal versus nanogroup-specific QSAR models (metal oxide and nanotubes), and regression versus classification Machine Learning (ML) algorithms. RESULTS: Universal regression and classification QSARs reached an 0.86 R2 and 0.92 accuracy, respectively, for the test set. Nanogroup-specific regression models reached 0.88 R2 for nanotubes test set followed by metal oxide (0.78). Nanogroup-specific classification models reached 0.99 accuracy for nanotubes test set, followed by metal oxide (0.91). Feature importance revealed different patterns depending on the dataset with common influential features including core size, exposure conditions and toxicological assay. Even in the case where the available experimental knowledge was merged, the models still failed to correctly predict the outputs of an unseen dataset, revealing the cumbersome conundrum of scientific reproducibility in realistic applications of QSAR for nanosafety. To harness the full potential of computational tools and ensure their long-term applications, embracing FAIR data practices is imperative in driving the development of responsible QSAR models. CONCLUSIONS: This study reveals that the digitalization of nanosafety knowledge in a reproducible manner has a long way towards its successful pragmatic implementation. The workflow carried out in the study shows a promising approach to increase the FAIRness across all the elements of computational studies, from dataset's annotation, selection, merging to FAIR modeling reporting. This has significant implications for future research as it provides an example of how to utilize and report different tools available in the nanosafety knowledge system, while increasing the transparency of the results. One of the main benefits of this workflow is that it promotes data sharing and reuse, which is essential for advancing scientific knowledge by making data and metadata FAIR compliant. In addition, the increased transparency and reproducibility of the results can enhance the trustworthiness of the computational findings.

Data-Driven Quantitative Intrinsic Hazard Criteria for Nanoproduct Development in a Safe-by-Design Paradigm: A Case Study of Silver Nanoforms.

The current European (EU) policies, that is, the Green Deal, envisage safe and sustainable practices for chemicals, which include nanoforms (NFs), at the earliest stages of innovation. A theoretically safe and sustainable by design (SSbD) framework has been established from EU collaborative efforts toward the definition of quantitative criteria in each SSbD dimension, namely, the human and environmental safety dimension and the environmental, social, and economic sustainability dimensions. In this study, we target the safety dimension, and we demonstrate the journey toward quantitative intrinsic hazard criteria derived from findable, accessible, interoperable, and reusable data. Data were curated and merged for the development of new approach methodologies, that is, quantitative structure-activity relationship models based on regression and classification machine learning algorithms, with the intent to predict a hazard class. The models utilize system (i.e., hydrodynamic size and polydispersity index) and non-system (i.e., elemental composition and core size)-dependent nanoscale features in combination with biological in vitro attributes and experimental conditions for various silver NFs, functional antimicrobial textiles, and cosmetics applications. In a second step, interpretable rules (criteria) followed by a certainty factor were obtained by exploiting a Bayesian network structure crafted by expert reasoning. The probabilistic model shows a predictive capability of ≈78% (average accuracy across all hazard classes). In this work, we show how we shifted from the conceptualization of the SSbD framework toward the realistic implementation with pragmatic instances. This study reveals (i) quantitative intrinsic hazard criteria to be considered in the safety aspects during synthesis stage, (ii) the challenges within, and (iii) the future directions for the generation and distillation of such criteria that can feed SSbD paradigms. Specifically, the criteria can guide material engineers to synthesize NFs that are inherently safer from alternative nanoformulations, at the earliest stages of innovation, while the models enable a fast and cost-efficient in silico toxicological screening of previously synthesized and hypothetical scenarios of yet-to-be synthesized NFs.

Additive-Free Gelatine-Based Devices for Chondral Tissue Regeneration: Shaping Process Comparison among Mould Casting and Three-Dimensional Printing.

Gelatine is a well-known and extensively studied biopolymer, widely used in recent decades to create biomaterials in many different ways, exploiting its molecular resemblance with collagen, the main constituent of the extra-cellular matrix, from which it is derived. Many have employed this biopolymer in tissue engineering and chemically modified (e.g., gelatin methacryloyl) or blended it with other polymers (e.g., alginate) to modulate or increase its performances and printability. Nevertheless, little is reported about its use as a stand-alone material. Moreover, despite the fact that multiple works have been reported on the realization of mould-casted and three-dimensional printed scaffolds in tissue engineering, a clear comparison among these two shaping processes, towards a comparable workflow starting from the same material, has never been published. Herein, we report the use of gelatine as stand-alone material, not modified, blended, or admixed to be processed or crosslinked, for the realization of suitable scaffolds for tissue engineering, towards the two previously mentioned shaping processes. To make the comparison reliable, the same pre-process (e.g., the gelatin solution preparation) and post-process (e.g., freeze-drying and crosslinking) steps were applied. In this study, gelatine solution was firstly rheologically characterized to find a formulation suitable for being processed with both the shaping processes selected. The realized scaffolds were then morphologically, phisico-chemically, mechanically, and biologically characterized to determine and compare their performances. Despite the fact that the same starting material was employed, as well as the same pre- and post-process steps, the two groups resulted, for most aspects, in diametrically opposed characteristics. The mould-casted scaffolds that resulted were characterized by small, little-interconnected, and random porosity, high resistance to compression and slow cell colonization, while the three-dimensional printed scaffolds displayed big, well-interconnected, and geometrically defined porosity, high elasticity and recover ability after compression, as well as fast and deep cell colonization.

Simple ions control the elasticity of calcite gels via interparticle forces.

Suspensions of calcite in water are employed in many industrial fields such as paper filling, pharmaceutics or heritage conservation. Whereas organics are generally used to tune the rheological properties of the paste, we also expect simple ions to be able to control the suspension rheology via the interparticle forces. We have thus investigated the impact of calcium, sodium and hydroxide ions on the elasticity of a colloidal gel of nanocalcite. We confront our macroscopic measurements to DLVO interaction potentials, based on chemical speciation and measurements of the zeta potential. Upon addition of calcium hydroxide, we observe a minimum in shear modulus, correlated to a maximum in the DLVO energy barrier, due to two competing effects: Calcium adsorption onto calcite surface rises the zeta potential, while increasing salt concentration induces stronger electrostatic screening. We also demonstrate that the addition of sodium hydroxide completely screens the surface charge and leads to a more rigid paste. A second important result is that carbonation of the calcite suspensions by the atmospheric CO2 leads to a convergent high elasticity of the colloidal gels, whatever their initial value, also well rationalized by DLVO theory and resulting from a decrease in zeta potential.

Silica modification of titania nanoparticles enhances photocatalytic production of reactive oxygen species without increasing toxicity potential in vitro.

Titania (TiO2) nanoparticles were surface modified using silica and citrate to implement a 'safe-by-design' approach for managing potential toxicity of titania nanoparticles by controlling surface redox reactivity. DLS and zeta-potential analyses confirmed the surface modification, and electron microscopy and surface area measurements demonstrated nanoscale dimensions of the particles. Electron paramagnetic resonance (EPR) was used to determine the exogenous generation of reactive oxygen species (ROS). All the produced spray dried nanotitania lowered levels of ROS when compared to the corresponding dispersed nanotitania, suggesting that the spray drying process is an appropriate design strategy for the control of nano TiO2 ROS reactivity. The modification of nanotitania with silica and with citrate resulted in increased levels of ROS generation in exogenous measurements, including photoexcitation for 60 minutes. The dichlorodihydrofluorescein (DCFH) assay of dose-dependent production of oxidative stress, generated by pristine and modified nanotitania in macrophages and alveolar epithelial cells, found no significant change in toxicity originating from the generation of reactive oxygen species. Our findings show that there is no direct correlation between the photocatalytic activity of nanotitania and its oxidative stress-mediated potential toxicity, and it is possible to improve the former, for example adding silica as a modifying agent, without altering the cell redox equilibrium.

Ceramic Ink-Jet Printing for Digital Decoration: Physical Constraints for Ink Design.

In the last decade, the drop-on-demand (DOD) ink-jet printing has become the leading technology for the decoration of ceramic tiles. The inks employed for such application are colloidal suspensions of oxide particles (0.3 µm) whose stability (against agglomeration and over time) is fundamental to get successfully the tile decoration. Jettability from the DOD print heads is a key requirement along with proper colour after sintering. This means that a careful set up of inks properties (viscosity, density, surface tension) is required. The phenomena involved in the different stages of the ink-jet printing process (drop ejection from the nozzles, impact and spreading on the substrates) are described through dimensionless numbers as Reynolds, Weber, and Bond numbers, or their combinations. In literature physical constraints, obtained with a semi-theoretical approach on the basis of experimental evidences on other systems, allow to define a reference region in the space of the dimensionless numbers (here called "printable fluid region," PFR) where the inks should be suitable for the application. In this paper, 26 inks currently used for ceramic tile decoration were characterized and mapped in the space of dimensionless numbers for several printing conditions. For typical nozzle diameters (20-50 gm) and drop velocities (6-8 m/s), it has been found that they fall in the region identified by 3 < Re < 30, 27 < We < 160, and 0.6 < 1/Oh < 2.5, where Re, We, and Oh, are the Reynolds, Weber and Ohnesorge numbers, respectively. Such experimental region can be taken as reference to tune the colloidal interactions in proper way, though the thresholds delimiting the PFR should be better defined.

Nano-sized ceramic inks for drop-on-demand ink-jet printing in quadrichromy.

Nano-sized ceramic inks suitable for ink-jet printing have been developed for the four-colours CMYK (cyan, magenta, yellow, black) process. Nano-inks of different pigment composition (Co(1-x)O, Au(0), Ti(1-x-y)Sb(x)Cr(y)O2, CoFe2O4) have been prepared with various solid loadings and their chemicophysical properties (particle size, viscosity, surface tension, zeta-potential) were tailored for the ink-jet application. The pigment particle size is in the 20-80 nm range. All these nano-suspensions are stable for long time (i.e., several months) due to either electrostatic (high zeta-potential values) or steric stabilization mechanisms. Both nanometric size and high stability avoid problems of nozzle clogging from particles agglomeration and settling. Nano-inks have a Newtonian behaviour with relatively low viscosities at room temperature. More concentrated inks fulfil the viscosity requirement of ink-jet applications (i.e., < 35 mPa x s) for printing temperatures in between 30 and 70 degrees C. Surface tension constraints for ink-jet printing are fulfilled by nano-inks, being in the 35-45 mN x m(-1) range. The nano-sized inks investigated behave satisfactorily in preliminary printing tests on several unfired industrial ceramic tiles, developing saturated colours in a wide range of firing temperatures (1000-1200 degrees C).

On the possibility of silicon nitride as a ceramic for structural orthopaedic implants. Part II: chemical stability and wear resistance in body environment.

In Part I, the processing, microstructure and mechanical properties of three silicon nitride-based ceramics were examined and their non-toxicity was demonstrated. In this Part II, some features critical to biomedical applications were investigated: (i) the wetting behaviour against aqueous media, including physiological solutions; (ii) the chemical stability in water and in physiological solutions; and (iii) the wear resistance, measured under experimental procedures that simulate the conditions typical of the hip joint prosthesis. The results confirmed that silicon nitride may serve as a biomaterial for bone substitution in load bearing prosthesis.