Integrate & balance aspects for safe and sustainable innovation: Needs analysis on SSbD categories and product development stage requirements to cover the entire life cycle.

Current EU Strategies aim to rapidly advance the research, development and deployment of innovative advanced materials and chemicals to make Europe the first digitally enabled circular, climate-neutral and sustainable economy. To achieve this, an underlying adaptation of the research and innovation (R&I) process to the Safety-and-Sustainability-by-Design (SSbD) framework has been proposed. This perspective article provides an overview of already existing approaches providing guidance for implementing SSbD-like procedures in R&I in several different industrial sectors to ultimately replace substances of concern (SoC).

AFM-Based Deep Learning Decodes Human Macrophage Mechanophenotypes.

Macrophage polarization into inflammatory (M1) and repairing/healing (M2) functional phenotypes are fundamental mechanisms in immune defensive responses, tissue repair, and disease control. Conventional phenotyping approaches based on molecular biomarkers are limited by destructive protocols, static endpoint analyses, and a disregard for the biomechanical attributes of cells. In this study, an integrated artificial intelligence (AI)-atomic force microscopy (AFM) platform is introduced that enables label-free, mechanophenotyping of macrophages at single-cell resolution.

Going digital to boost safe and sustainable materials innovation markets. The digital safe-and-sustainability-by-design innovation approach of the PINK project.

In this innovation report, we present the vision of the PINK project to foster Safe-and-Sustainable-by-Design (SSbD) advanced materials and chemicals (AdMas&Chems) development by integrating state-of-the-art computational modelling, simulation tools and data resources. PINK proposes a novel approach for the use of the SSbD Framework, whose innovative approach is based on the application of a multi-objective optimisation procedure for the criteria of functionality, safety, sustainability and cost efficiency. At the core is the PINK open innovation platform, a distributed system that integrates all relevant modelling resources enriched with advanced data visualisation and an AI-driven decision support system.

Instance maps as an organising concept for complex experimental workflows as demonstrated for (nano)material safety research.

Nanosafety assessment, which seeks to evaluate the risks from exposure to nanoscale materials, spans materials synthesis and characterisation, exposure science, toxicology, and computational approaches, resulting in complex experimental workflows and diverse data types. Managing the data flows, with a focus on provenance (who generated the data and for what purpose) and quality (how was the data generated, using which protocol with which controls), as part of good research output management, is necessary to maximise the reuse potential and value of the data. Instance maps have been developed and evolved to visualise experimental nanosafety workflows and to bridge the gap between the theoretical principles of FAIR (Findable, Accessible, Interoperable and Re-usable) data and the everyday practice of experimental researchers.

Application of the market-ready NAVETTA electrodeposition chamber for controlled exposure with nano-scaled aerosols.

Exposure of lung epithelia to aerosols is omnipresent. Chronic exposure to polluted air is a significant factor in the development of pulmonary diseases, which are among the top global causes of death, including COVID-19, chronic obstructive pulmonary disease, lung cancer, and tuberculosis. As efforts to prevent and treat lung diseases increase, the development of pulmonary drug delivery systems has become a major area of interest.

Roadmap towards safe and sustainable advanced and innovative materials. (Outlook for 2024-2030).

The adoption of innovative advanced materials holds vast potential, contingent upon addressing safety and sustainability concerns. The European Commission advocates the integration of Safe and Sustainable by Design (SSbD) principles early in the innovation process to streamline market introduction and mitigate costs. Within this framework, encompassing ecological, social, and economic factors is paramount.

Re-assessment of monoclonal antibodies against diclofenac for their application in the analysis of environmental waters.

The non-steroidal anti-inflammatory drug (NSAID) diclofenac (DCF) is an important environmental contaminant occurring in surface waters all over the world, because, after excretion, it is not adequately removed from wastewater in sewage treatment plants. To be able to monitor this pollutant, highly efficient analytical methods are needed, including immunoassays. In a medical research project, monoclonal antibodies against diclofenac and its metabolites had been produced.

Antiviral Activity of Zinc Oxide Nanoparticles against SARS-CoV-2.

The highly contagious SARS-CoV-2 virus is primarily transmitted through respiratory droplets, aerosols, and contaminated surfaces. In addition to antiviral drugs, the decontamination of surfaces and personal protective equipment (PPE) is crucial to mitigate the spread of infection. Conventional approaches, including ultraviolet radiation, vaporized hydrogen peroxide, heat and liquid chemicals, can damage materials or lack comprehensive, effective disinfection.

Heterogeneity of Lipopolysaccharide as Source of Variability in Bioassays and LPS-Binding Proteins as Remedy.

Lipopolysaccharide (LPS), also referred to as endotoxin, is the major component of Gram-negative bacteria's outer cell wall. It is one of the main types of pathogen-associated molecular patterns (PAMPs) that are known to elicit severe immune reactions in the event of a pathogen trespassing the epithelial barrier and reaching the bloodstream. Associated symptoms include fever and septic shock, which in severe cases, might even lead to death.

EVAnalyzer: High content imaging for rigorous characterisation of single extracellular vesicles using standard laboratory equipment and a new open-source ImageJ/Fiji plugin.

Extracellular vesicle (EV) research increasingly demands for quantitative characterisation at the single vesicle level to address heterogeneity and complexity of EV subpopulations. Emerging, commercialised technologies for single EV analysis based on, for example, imaging flow cytometry or imaging after capture on chips generally require dedicated instrumentation and proprietary software not readily accessible to every lab. This limits their implementation for routine EV characterisation in the rapidly growing EV field.

Immunotoxicity of nanomaterials in health and disease: Current challenges and emerging approaches for identifying immune modifiers in susceptible populations.

Nanosafety assessment has experienced an intense era of research during the past decades driven by a vivid interest of regulators, industry, and society. Toxicological assays based on in vitro cellular models have undergone an evolution from experimentation using nanoparticulate systems on singular epithelial cell models to employing advanced complex models more realistically mimicking the respective body barriers for analyzing their capacity to alter the immune state of exposed individuals. During this phase, a number of lessons were learned.

(Re)Conceptualizing decision-making tools in a risk governance framework for emerging technologies-the case of nanomaterials.

The utility of decision-making tools for the risk governance of nanotechnology is at the core of this paper. Those working in nanotechnology risk management have been prolific in creating such tools, many derived from European FP7 and H2020-funded projects. What is less clear is how such tools might assist the overarching ambition of creating a fair system of risk governance.

Surface Functionalization of Silica Nanoparticles: Strategies to Optimize the Immune-Activating Profile of Carrier Platforms.

Silica nanoparticles (SiNPs) are generally regarded as safe and may represent an attractive carrier platform for nanomedical applications when loaded with biopharmaceuticals. Surface functionalization by different chemistries may help to optimize protein loading and may further impact uptake into the targeted tissues or cells, however, it may also alter the immunologic profile of the carrier system. In order to circumvent side effects, novel carrier candidates need to be tested thoroughly, early in their development stage within the pharmaceutical innovation pipeline, for their potential to activate or modify the immune response.

Blueprint for a self-sustained European Centre for service provision in safe and sustainable innovation for nanotechnology.

The coming years are expected to bring rapid changes in the nanotechnology regulatory landscape, with the establishment of a new framework for nano-risk governance, in silico approaches for characterisation and risk assessment of nanomaterials, and novel procedures for the early identification and management of nanomaterial risks. In this context, Safe(r)-by-Design (SbD) emerges as a powerful preventive approach to support the development of safe and sustainable (SSbD) nanotechnology-based products and processes throughout the life cycle. This paper summarises the work undertaken to develop a blueprint for the deployment and operation of a permanent European Centre of collaborating laboratories and research organisations supporting safe innovation in nanotechnologies.

Nanomaterial Exposure, Extracellular Vesicle Biogenesis and Adverse Cellular Outcomes: A Scoping Review.

The progressively increasing use of nanomaterials (NMs) has awakened issues related to nanosafety and its potential toxic effects on human health. Emerging studies suggest that NMs alter cell communication by reshaping and altering the secretion of extracellular vesicles (EVs), leading to dysfunction in recipient cells. However, there is limited understanding of how the physicochemical characteristics of NMs alter the EV content and their consequent physiological functions.

The nanotopography of SiO particles impacts the selectivity and 3D fold of bound allergens.

A detailed description of the changes that occur during the formation of protein corona represents a fundamental question in nanoscience, given that it not only impacts the behaviour of nanoparticles but also affects the bound proteins. Relevant questions include whether proteins selectively bind particles, whether a specific orientation is preferred for binding, and whether particle binding leads to a modulation of their 3D fold. For allergens, it is important to answer these questions given that all these effects can modify the allergenic response of atopic individuals.

Children's Privilege in COVID-19: The Protective Role of the Juvenile Lung Morphometry and Ventilatory Pattern on Airborne SARS-CoV-2 Transmission to Respiratory Epithelial Barriers and Disease Severity.

The incidence of severe COVID-19 in children is low, and underlying mechanisms for lower SARS-CoV-2 susceptibility and self-limiting disease severity are poorly understood. Severe clinical manifestations in adults require SARS-CoV-2 inoculation in the lower respiratory tract, establishing a pulmonary disease phase. This may be either accomplished by direct inoculation of the thoracic region upon exposure to virion-laden aerosols, or by infection of the upper respiratory system and aspiration of virion-laden aerosols originating right there into the lower respiratory tract.

Structural Alterations of Antigens at the Material Interface: An Early Decision Toolbox Facilitating Safe-by-Design Nanovaccine Development.

Nanomaterials have found extensive interest in the development of novel vaccines, as adjuvants and/or carriers in vaccination platforms. Conjugation of protein antigens at the particle surface by non-covalent adsorption is the most widely used approach in licensed particulate vaccines. Hence, it is essential to understand proteins' structural integrity at the material interface in order to develop safe-by-design nanovaccines.

Iron Oxide Nanoparticles in Bioimaging - An Immune Perspective.

Iron oxide nanoparticles (IONPs) bear big hopes in nanomedicine due to their (potential) applications in tumor therapy, drug delivery or bioimaging. However, as foreign entities, such particles may be recognized by the immune system and, thus, lead to inflammation, hypersensitivity or anaphylactic shock. In addition, an overload with iron is known to cause oxidative stress.

SARS-CoV-2-Laden Respiratory Aerosol Deposition in the Lung Alveolar-Interstitial Region Is a Potential Risk Factor for Severe Disease: A Modeling Study.

COVID-19, predominantly a mild disease, is associated with more severe clinical manifestation upon pulmonary involvement. Virion-laden aerosols and droplets target different anatomical sites for deposition. Compared to droplets, aerosols more readily advance into the peripheral lung.

The Impact of Nanoparticles on Innate Immune Activation by Live Bacteria.

The innate immune system evolved to detect and react against potential dangers such as bacteria, viruses, and environmental particles. The advent of modern technology has exposed innate immune cells, such as monocytes, macrophages, and dendritic cells, to a relatively novel type of particulate matter, i.e.

Can an InChI for Nano Address the Need for a Simplified Representation of Complex Nanomaterials across Experimental and Nanoinformatics Studies?

Chemoinformatics has developed efficient ways of representing chemical structures for small molecules as simple text strings, simplified molecular-input line-entry system (SMILES) and the IUPAC International Chemical Identifier (InChI), which are machine-readable. In particular, InChIs have been extended to encode formalized representations of mixtures and reactions, and work is ongoing to represent polymers and other macromolecules in this way. The next frontier is encoding the multi-component structures of nanomaterials (NMs) in a machine-readable format to enable linking of datasets for nanoinformatics and regulatory applications.

Metadata Stewardship in Nanosafety Research: Community-Driven Organisation of Metadata Schemas to Support FAIR Nanoscience Data.

The emergence of nanoinformatics as a key component of nanotechnology and nanosafety assessment for the prediction of engineered nanomaterials (NMs) properties, interactions, and hazards, and for grouping and read-across to reduce reliance on animal testing, has put the spotlight firmly on the need for access to high-quality, curated datasets. To date, the focus has been around what constitutes data quality and completeness, on the development of minimum reporting standards, and on the FAIR (findable, accessible, interoperable, and reusable) data principles. However, moving from the theoretical realm to practical implementation requires human intervention, which will be facilitated by the definition of clear roles and responsibilities across the complete data lifecycle and a deeper appreciation of what metadata is, and how to capture and index it.