Treatment resistance and recurrence continue to define the clinical landscape of glioblastoma (GBM), yet their study is limited by traditional in vitro frameworks that fail to capture long-term treatment dynamics and tumor evolution. Here we present GliaMimic, a longitudinal in vitro platform incorporating irradiation and multi-dose temozolomide (TMZ). Using patient-derived organoids (PDOs) and cell line-derived spheroids, tumor progression and treatment response were monitored non-invasively over four weeks. Substantial declines in metabolic activity and viability at clinically relevant TMZ concentrations (≤ 10 µM) emerge only after prolonged exposure, whereas short-term assays captured effects only at supraphysiological doses. Notably, PDOs, patient-derived spheroids, and their cell line-derived counterparts exhibited distinct patterns of treatment response and tumor progression, underscoring the importance of model selection in preclinical studies. Following treatment cessation, the platform captured distinct, patient-specific post-treatment tumor behaviors with persistent viable and metabolically active populations across all models with more pronounced changes in PDOs. By moving beyond static molecular diagnostics, GliaMimic provides a longitudinal in vitro treatment evaluation platform for preclinical testing.

Ti3C2Tx MXene is a two-dimensional material with exceptional electrical conductivity, rendering them promising candidates as ink for printable skin biosensors. However, their susceptibility to oxidation under biologically relevant conditions and the consequences of oxidation on material properties remain unclear, posing challenges for practical applications. The skin is the barrier to the external environment. Its microenvironment, including sweat, may influence MXenes stability and behavior. Rigorous dermal safety assessment is therefore essential before MXenes widespread use. In this study, we systematically investigated the oxidation kinetics of Ti3C2Tx MXenes with different flake sizes in biologically relevant solutions under varying temperatures and light exposure. Our results showed that oxidation was accelerated primarily by ionic strength and temperature. To prolong the lifetime of MXenes, we evaluated common antioxidant skincare ingredients vitamin E, niacinamide, and N-acetyl cysteine, finding that vitamin E significantly slowed oxidation in dispersions. To assess oxidation-dependent toxicity, we examined skin irritation and sensitization induced by freshly synthesized, partially oxidized, and fully oxidized MXenes. Accordingly, MXene dispersions were pre-incubated to obtain partially and fully oxidized samples. Oxidation was defined by the loss of the plasmonic band in the UV-Vis spectrum, a functional readout linked to conductivity, and thus relevant to the intended application of MXenes. Then, dermal toxicity was assessed using the KeratinoSens® assay and reconstituted human scaffold-free skin cultures. Across all oxidation states, Ti3C2Tx MXenes did not induce statistically significant skin irritation or sensitization. Furthermore, cellular uptake and mechanistic insights were explored by using confocal Raman spectroscopy and flow cytometry, showing Ti3C2Tx MXene internalization and reduction in intracellular reactive oxygen species level. Together, these findings reveal the oxidation behavior of Ti3C2Tx MXenes, identify a practical strategy to extend their functional lifetime, and establish dermal safety profiles under potential application relevant conditions, providing key intermediate evidence for future safe and sustainable biomedical applications.

Abstract In vitro pulmonary models are widely used for safety evaluations, simulating human lung responses to inhaled particles or chemicals. These models help detect toxicity early, reducing the need for animal testing. In this study, we used two models: the Alveolar Macrophage Assay (AMA), a simple model, and the tissue model MucilAir™, a more robust system, to evaluate the safety of commercial carbon-based spray lubricants. We also characterized the lubricants to identify their physico-chemical properties but encountered difficulties due to interference from the silicone-based lubricant matrix. Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) analysis could not detect carbon-based materials, likely due to the presence of polysiloxanes. Confocal Raman analysis revealed graphite, with minor contributions from graphene, which was consistent with Scanning Electron Microscopy (SEM) findings showing graphite-like particles. Exposure assessment revealed that spray droplets approximately 2.20 µm in size are released during application, suggesting inhalation as a potential exposure route. Hazard assessment using AMA was challenging; direct spray administration onto MucilAir™ caused cell damage or death. The submerged approach with macrophages led to density-driven separation of compounds, but a black material was partially incorporated into cells, triggering a dose-dependent release of lytic enzymes. Despite challenges in characterising and testing graphene-based lubricants, MucilAir™ was shown to be a sensitive model for assessing the safety of such products. A tailored approach, considering specific properties of lubricants, is critical for accurate hazard assessment. The MACRAME project was funded by the EU Horizon Europe (GA no 101092686), Swiss SERI (no 23.00141), and UKRI Innovate (no 10066165).

Intravenous iron-carbohydrate complexes are widely used nanomedicines for the treatment of iron deficiency anaemia, particularly in patients with conditions like chronic kidney disease, heart failure and inflammatory diseases. Despite the abundance of physicochemical characterization and clinical studies for these products, a clear evidence-based correlation between physicochemical properties and clinical outcome of iron-carbohydrate complexes is yet to be established. There is, nonetheless, clear evidence that the nano-bio interface determines the bio-response and mode of action. Here, the early interactions between iron-carbohydrate nanomedicines and blood components are investigated using time-resolved small-angle X-ray and neutron scattering (SAXS and SANS, respectively) under flow conditions enabled by a microfluidic device. Two clinically relevant iron-carbohydrate complexes with different carbohydrate ligand morphologies, iron sucrose (IS) and ferric carboxymaltose (FCM), were studied for their early interactions (down to minutes) with human serum albumin (HSA) and human blood serum (HBS). When mixed with HSA, IS showed rapid agglomeration behavior at the nanoscale, as evidenced by a characteristic up-turn in the low-q region of the scattering curves, whereas FCM showed much slower agglomeration. With HBS, IS displayed a similar agglomeration behavior to that observed with HSA. In contrast, FCM showed increasingly repulsive interactions amongst its clusters in blood serum, reflected by a characteristic down-turn in the low-q scattering, associated with improved colloidal stability. These results demonstrate that early nano-bio interactions are strongly formulation-dependent and governed by differences in the carbohydrate shell architecture. These findings provide a physicochemical framework for the design of future cell-based and mechanistic studies aimed at bridging physicochemical properties with clinical outcomes.

Abstract Wound and device-associated infections remain difficult to eradicate because biofilms block host immunity and antibiotics, accelerating chronicity and resistance. Here, we present a portable, low-cost dual-syringe spray that deposits an ultra-thin, self-assembling antimicrobial film directly on wounds and implant surfaces. The device co-delivers oppositely charged hyaluronic acid (HA) and a cationic antimicrobial peptide (polyarginine, PAR30), which rapidly form a conformal nanometric polyelectrolyte complex at the tissue-material interface. Molecular dynamics simulation revealed pronounced positional heterogeneity within the PAR30/HA complex and identified an N-terminal arginine as a dominant interaction hotspot. The resulting coating adheres to diverse substrates, kills bacteria on contact, prevents biofilm formation, and sustains antimicrobial efficacy. Across vitro assays and murine wound infection models, treatment produced 4 to 5 log reductions in bacterial burden against methicillin-resistant Staphylococcus aureus and Gram-negative pathogens, including Pseudomonas aeruginosa and Escherichia coli . The formulation is biocompatible, did not increase cutaneous inflammation or IL-6 levels in vivo , and reduced post-surgical pain and motor deficits in a mouse incision model. To our knowledge, this is the first antimicrobial treatment system applicable to both tissues and medical devices. Developed under a safe-and-sustainable-by-design approach, this technology combines biocompatible components, nanometric coating for minimal material use, and a simple syringe-based delivery device, offering a scalable, antibiotic-free strategy for wound care and medical device infection prevention. Graphical abstract

Abstract Indoor air pollution from airborne micro- and nanoplastics, as well as natural particulate matter, is an emerging health concern. Released textile fibres and debris (eg during washing, drying, wearing) are a significant yet understudied source of this pollution. These fibbers, originating from synthetic, biobased, and natural fabrics, can be inhaled into the lungs. Particularly smaller fibres and debris (<3 um) can reach deeper lung regions, potentially posing risks to human respiratory health. Yet, the chronic effects of long-term exposure to environmentally relevant fibre concentrations in human lungs remain poorly understood. This project aims to investigate the long-term impact of inhaled textile fibers and debris on respiratory health using advanced reconstituted 3D in vitro lung models. We focus on synthetic, biobased and natural fibres under repeated subtoxic exposure conditions that simulate realistic human exposure scenarios. To achieve this, textiles undergo a controlled water-based gyrowash extraction (40°C, 45 min) and the released fibres and debris are collected, systematically characterized for their physicochemical properties and subjected to a comprehensive toxicological analysis. We will assess cell viability, ciliary function, mucociliary clearance, barrier integrity, and inflammatory responses. Specific endpoints include barrier tightness, cytokine production, and activation of inflammatory pathways, complemented by multiomics approaches to uncover toxicity mechanisms. The role of environmental pollutants adsorbed onto released fibres—particularly their interaction with the lung environment and their potential to amplify toxic and inflammatory effects—will also be investigated. This approach will enable fibre-specific hazard profiling and support realistic exposure and risk assessments.

Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by high recurrence rates and poor prognosis despite multimodal treatment. Understanding the mechanisms underlying GBM relapse is crucial for developing more effective therapeutic strategies. In vitro relapse models provide controlled environments to investigate tumor recurrence, therapeutic resistance, and disease progression. This review explores the spectrum of in vitro models that have been established to study human GBM relapse, including 2D cultures, 3D spheroids/organoids, microfluidic and organ-on-a-chip systems. Among the key findings, it is determined that developing in vitro GBM relapse models requires the replication of longitudinal and clinically adapted treatment regimes, assessment of therapeutic efficacy under relapse conditions, and the incorporation of treatment discontinuation phases to permit tumor regrowth and relapse formation. The integration of these findings enabled the conceptualization and design of an advanced in vitro GBM relapse system, establishing a roadmap for future relapse research. By strategically employing representative GBM relapse models, researchers can both identify patient-specific therapies to prevent relapse and validate promising treatments for recurrent disease. This crucial work bridges the gap between experimental models and patient outcomes, advancing precision medicine for recurrent GBM.

Abstract Two-dimensional (2D) graphene-based advanced materials are increasingly utilized across a wide range of applications, including battery technology, superconductors, biomedical products, and catalysis. As their use expands, so does the potential for human exposure, particularly in occupational environments during production, as well as during end-of-life handling. Inhalation represents a major route of exposure for workers in these settings. Here, we aimed to investigate potential inhalation-related health hazards of few-layer graphene (FLG; Carbon Waters)-epoxy composites using alveolar macrophages (NR8383) and ALIsens, AlveolAirTM and MucilAirTM advanced in vitro lung cell culture models. The results demonstrate successful detection of FLG in the epoxy (product) matrix by using Raman spectroscopy and time-of-flight secondary ion mass spectrometry (TOF-SIMS) techniques. The alveolar macrophage assay demonstrated material-specific variations in bioresponse. Pristine FLG did not impact macrophage viability but induced a pronounced secretion of the pro-inflammatory cytokine TNFα. In contrast, particles collected after abrasion of FLG-epoxy composites showed no significant upregulation in TNFα response but induced dose-dependent cytotoxicity in alveolar macrophages. In the bronchial and alveolar airway epithelial cultures, pristine FLG and abraded particles did not decrease cell viability or compromise barrier integrity, but a moderate reduction of mucociliary clearance was observed at concentrations above 10 µg/cm2, which was further confirmed with scanning electron microscopy (SEM). Overall, our data reveals distinct health risks associated with particle inhalation during FLG-epoxy composite production and degradation, affecting multiple lung cell types. These findings provide valuable mechanistic insights to support health hazard assessment and safe-by-design development of industrial graphene-based composite materials.

The large-scale production, marketing and disposal of polymer-based graphene products can lead to the dispersal of graphene-enriched plastic particles into terrestrial ecosystems, where they might accumulate if not degraded by organisms. The objective of this work is to test the degradability and compatibility of one polyamide-6 polymer reinforced with reduced graphene-oxide (PA6-rGO) and its base constituents (polyamide-6, PA6; reduced graphene oxide, rGO) using mono- and co-cultures of two lignin-degrading fungi (Bjerkandera adusta and Morchella esculenta) grown under different nutrient conditions. Fungal (co-)cultures were exposed to pure rGO or abraded powders of PA6 and PA6-rGO in two different liquid media, and monitored over time for biomass growth, H2O2 production, and activity of two lignolytic enzymes (i.e, Laccase, Lac, and Lignin peroxidase, LiP). The changes in polyamide structure were evaluated by proton nuclear magnetic resonance and mass spectrometry, and changes in rGO were evaluated by Raman spectroscopy. The materials had no effect on fungal growth. PA6 increased Lac secretion only in low nutrient medium, while PA6-rGO slightly suppressed LiP activity. Only M. esculenta promoted polyamides oxidation when cultured in a low nutrient medium, as evidenced by a change in mass distribution values (m/z: 400-420) and the appearance of a new resonance peak (at 5.37 ppm). Lignolytic exudates in co-cultures low in nutrients caused a greater change in rGO, as shown by the increase in the ID/IG ratio. The degradation of rGO, PA6 and PA6-rGO depended on culture conditions.

Rapid innovation in chemicals and materials calls for innovative integrated approaches that can assess their impacts across different areas. The Safe and Sustainable-by-Design (SSbD) framework, developed by the European Commission's Joint Research Centre (JRC), offers a comprehensive approach with which to evaluate the safety and sustainability of chemicals and materials across their lifecycle. While SSbD uses various modeling approaches to assess impacts on human health, the environment, and socioeconomic factors, these are often applied independently, hindering a holistic understanding of the complex interactions between these factors and thus the simultaneous optimization of function, cost, safety and sustainability. This review describes existing predictive models and available strategies for their integration to facilitate more comprehensive and holistic chemical and material impact assessments. Specifically, we examine three model integration strategies: consensus integration that combines model predictions for the same impact categories, weighted aggregation that combines different scores in a unified one, and pipeline integration that links models sequentially to create a more unified assessment. Furthermore, we address key concepts related to the uncertainty of model predictions and the applicability domain of models, highlighting how these evolve in integrated frameworks. Insights into the applications of these integration strategies and challenges will allow a more accurate, coherent, and sustainable approach to chemical and material safety and sustainability assessments.

The Horizon Europe Project MACRAMÉ developed twelve recommendations towards Test Guidelines and Standards for safety assessment of advanced materials (AdMas) that capture the identified needs in characterisation and identification, safety testing, transformation and release as well as information flow along the AdMas lifecycle. MACRAMÉ highlights challenges posed by complex structures and transformations of AdMas and AdMas-enabled products for regulation and industry drawn on research on graphene-related materials, carbon nanotubes and poly(lactic-co-glycolic) acid in realistic use cases. MACRAMÉ translates advances in characterisation, transformation and release assessment, and New Approach Methodologies into actionable recommendations and calls on regulators, funding bodies, researchers and industry to develop and validate fit-for-purpose test methods, standards and guidance with the aim to enable safe and sustainable deployment of AdMas for societal challenges.

Abstract Mucociliary clearance in the upper respiratory tract serves as a critical component of the innate immune defence, protecting the lungs from inhaled environmental agents. Disruption of this function increases vulnerability to respiratory infections and chronic diseases. While certain nanomaterials are known to induce pulmonary fibrosis and inflammation, their potential to impair mucociliary function remains insufficiently understood. This study investigated the interactions of silicon- and carbon-based nanomaterials, including silicon carbide nanowires (SiC NWs), silicon dioxide (SiO2), quartz silica DQ12, multiwalled carbon nanotubes (MWCNTs), and graphene nanosheets, with human airway mucus and primary human bronchial epithelial cells. Among the evaluated nanomaterials, only SiC NWs were able to penetrate through the mucus barrier, due to their low silanol group density and hydrophobic surface, which reduced interactions with mucus components. Four consecutive days of repeated exposure of primary human bronchial epithelial cultures to SiC NWs resulted in significant (P < 0.05) impairment of mucociliary clearance, accompanied by abnormal ciliary morphology. Gene expression analysis revealed upregulation of FOXJ1, indicating dysregulated ciliogenesis. Additionally, SiC NWs compromised epithelial barrier integrity and induced pro-inflammatory and pro-fibrotic responses. These findings identify SiC NWs as uniquely capable of penetrating the mucus barrier and disrupting mucociliary clearance function, thereby highlighting a previously underrecognized mechanism of nanomaterial-induced respiratory toxicity. This work underscores the need for careful evaluation of nanomaterial physicochemical properties in relation to airway defence mechanisms.

ABSTRACT The increasing emergence of antimicrobial resistance and the development of new infective viral strains represent a constantly growing threat. Metal‐based nanomaterials have emerged as promising tools in the fight against bacterial and viral infections; however, the release of metal nanoparticles/ions in clinical applications may cause undesired side effects (allergies, systemic toxicity), reducing their practical use in antimicrobial treatment. Moreover, the metal‐based nanoparticles possess predominantly antibacterial effects, while their antiviral efficiency remains controversial. Thus, the development of metal‐free strategies enabling combined antibacterial/antiviral properties is a significant challenge. Here, we report a strategy based on light irradiation of nitrogen‐doped graphene acid (NGA) possessing dual photothermal and photodynamic modes of action. The antimicrobial activity is activated through a clinically approved near‐infrared (NIR) light source, and both viral and bacterial spreading can be hampered on the coating irradiation on a scale of minutes (5 to 10 min). The developed metal‐free strategy reduced 90.9% and 99.99% for S. aureus and P. aeruginosa, respectively, as well as 99.97% for murine hepatitis virus. Importantly, this research represents a significant advancement in the development of safe, metal‐free, and effective antimicrobial treatments. NGA coatings are safe for skin, showing no sensitization or irritation, and offer significant potential for advanced antimicrobial treatments.

Purpose :To investigate the light transmission (LT) of UV-A and green light through infected corneas saturated with riboflavin or rose bengal in an ex vivo porcine model for infectious keratitis. Setting: University of Zurich, Zurich, Switzerland, and Empa, St. Gallen, Switzerland. Design: Laboratory study. Methods: Ex vivo porcine eyes (n = 162) were divided into 3 groups: control eyes, eyes infected with Staphylococcus aureus, and eyes infected with Pseudomonas aeruginosa. Corneas remained either uninfected or were infected with S. aureus and P. aeruginosa and were either left untreated or were instilled with 0.1% riboflavin or 0.1% rose bengal. Corneal buttons were prepared, and corneal LT was measured at 365 nm and 522 nm using a spectrophotometer. LT values were calculated and compared. Transmission electron microscopy (TEM) was used to visualize structural damage and bacteria within infected corneas. Results: Riboflavin-saturated corneas infected by S. aureus or P. aeruginosa (LT = 0.77% [0.41-1.87] and 0.81% [0.23, 1.46]) exhibited 3.18-fold and 3.02-fold lower LT values, respectively, than uninfected corneas (LT = 2.45% [2.15, 5.89]) (both P-values < 0.001). No LT difference was found between rose bengal-saturated corneas infected by S. aureus or P. aeruginosa and uninfected corneas (all LT values = 0.01% [0.01-0.01]; both P-values = 0.08). TEM showed bacteria on corneal stroma borders and occasionally inside the stroma. Conclusions: The results indicate that the amount of light arriving at the corneal endothelium is substantially reduced in infected corneas. The total fluence of clinical photoactivated chromophore for keratitis corneal crosslinking protocols can be safely increased substantially while maintaining a low risk of corneal endothelial damage.

The development of new approach methodologies (NAMs) to replace current in vivo testing for the safety assessment of engineered nanomaterials (ENMs) is hindered by the scarcity of validated experimental data for many ENMs. We introduce a framework to address this challenge by harnessing the collective expertise of professionals from multiple complementary and related fields ("wisdom of crowds" or WoC). By integrating expert insights, we aim to fill data gaps and generate consensus concern scores for diverse ENMs, thereby enhancing the predictive power of nanosafety computational models. Our investigation reveals an alignment between expert opinion and experimental data, providing robust estimations of concern levels. Building upon these findings, we employ predictive machine learning models trained on the newly defined concern scores, ENM descriptors, and gene expression profiles, to quantify potential harm across various toxicity end points. These models further reveal key genes potentially involved in underlying toxicity mechanisms. Notably, genes associated with metal ion homeostasis, inflammation, and oxidative stress emerge as predictors of ENM toxicity across diverse end points. This study showcases the value of integrating expert knowledge and computational modeling to support more efficient, mechanism-informed, and scalable safety assessment of nanomaterials in the rapidly evolving landscape of nanotechnology.

Glioma, a highly aggressive brain tumor, presents significant challenges in understanding its complex pathophysiology and developing effective treatments. This review critically examines the current glioma modeling platforms, including 2D culture, 3D cultures, glioma‐on‐a‐chip (GoC) models, and animal models, with a focus on their applications in recapitulating the tumor microenvironment and evaluating treatment effectiveness. Particular attention is given to microfluidic GoC models, which offer unique capabilities to mimic the pathophysiological complexity of glioblastoma, including its interactions with the blood–brain barrier (BBB) and tumor vascularization. Recent advancements in these models are explored, highlighting their potential for clinical translation through improved understanding of drug permeability on the central nervous system, tumor progress, and therapeutic responses. In the end, the review discusses the clinical perspective of GoC applications and establishes key criteria for designing robust and clinically relevant glioma models. By addressing these challenges and highlighting future opportunities, the critical role of GoC platforms in bridging the gap between preclinical research and clinical outcomes is emphasized, offering a promising approach for more personalized and effective glioma therapies.

Traditional in vivo methodologies have long formed the foundation of chemical and material safety assessment, yet they are increasingly inadequate to meet modern regulatory, ethical, and sustainability demands. These conventional approaches are resource-intensive, ethically questionable, and often fail to accurately predict human or environmental toxicity, particularly for emerging pollutants such as PFAS, (nano-) pesticides, and 2D materials. In response, the EU has launched initiatives like the Chemical Strategy for Sustainability and the Zero Pollution Action Plan under the European Green Deal to promote innovation in safer, and more sustainable chemicals. Central to this transformation is the Safe and Sustainable by Design (SSbD) framework, developed by the European Commission’s Joint Research Center, which provides structured methodologies and metrics to integrate safety and sustainability into material innovation from the earliest stages of design.Building on this vision, the CHIASMA project aims to advance Next generation Safety Assessment (NGSA) by developing innovative New Approach Methodologies (NAMs) that combine experimental, computational, and Life Cycle Assessment (LCA) tools. Focusing on key biological systems and exposure routes, CHIASMA integrates Artificial Intelligence (AI), Machine Learning (ML), and Knowledge Graph (KG) technologies to enhance data interoperability and predictive accuracy. By embedding FAIR data principles and aligning with Good Laboratory Practice (GLP) standards, CHIASMA promotes transparency and regulatory acceptance. Fully aligned with SSbD principles, CHIASMA establishes a digital, interoperable infrastructure for predictive safety evaluation, that leverage on state-of-art experimental New Approach Methodologies (NAMs) bridging critical data gaps and supporting the transition towards sustainable, science-driven, and ethically responsible chemical and material innovation in Europe and beyond.

For the successful commercial development of emerging 2D materials, it is crucial to understand their potential biological effects on healthy and diseased individuals. The present study demonstrates that a repeated low‐dose (1 µg cm −2 for 5 weeks) exposure of primary human broncho‐epithelial (HBE) cell cultures to hexagonal boron nitride nanosheets ( h ‐BN) and boron nitride nanotubes (BNNTs) increases the phospholipid, sphingolipid, and diglyceride content in cell membranes. Global lipidomics profiling further shows the induction of lipid mediator biosynthesis, especially after exposure to BNNTs in asthmatic cell cultures. The significant increase in leukotriene biosynthesis including its extracellular release is also confirmed in vivo in exposed mouse lungs. Mechanistically, extracellular release of lipid mediators prompts the recruitment and activation of immune cells. Mass cytometry‐based single‐cell profiling of human peripheral blood mononuclear cells reveals the activation of distinct lymphocyte populations expressing cytotoxic granzyme B and perforin mainly after exposure to conditioned medium from BNNT‐exposed asthmatic HBE cultures. These findings unveil the sub‐cytotoxic impact of BN nanomaterials on cellular lipid homeostasis and associated immunomodulation from repeated‐dose exposures, which may pose a potential health hazard, particularly for immune‐compromised individuals, and therefore, needs to be considered for the responsible and sustainable production and use of BN‐based products.

Ensuring the safety and sustainability of advanced materials (AdMas) is critical for fostering innovation while protecting human health and the environment. As industries integrate AdMas into commercial products to innovate in the next stage of the value chains, there is an urgent need for robust methodologies to detect, characterize, and assess their potential risks throughout their life cycle. The MACRAMÉ Project addresses this challenge by advancing standardized testing and regulatory frameworks, supporting the EU's vision for a toxic-free environment. Through cutting-edge research and international collaboration, MACRAMÉ lays the groundwork for reliable hazard assessment, regulatory compliance, and the responsible development of next-generation materials. The MACRAMÉ Project aims to enhance the detection, characterization, and quantification of Advanced Materials (AdMas) throughout their life cycle, assessing potential human and environmental health impacts during exposure. By developing, demonstrating, and standardizing advanced methodologies, MACRAMÉ ensures their broad applicability across market-relevant AdMas-containing products. Fully aligned with EU strategies such as the Chemical Strategy for Sustainability and the European Green Deal, the project extends nanosafety approaches to the broader AdMas category, focusing on inhalable carbon-based materials - graphene-related materials, carbon nanofibers, and poly lactic-co-glycolic acid nanoparticles. Building on over 15 years of research, MACRAMÉ integrates knowledge from major European and international initiatives to establish harmonized test guidelines, guidance documents, and standards. Through five industrial Use-Cases, the project applies innovative sample preparation, detection, and toxicity assessment techniques to develop a tiered approach for AdMa safety testing. Centralized in the MACRAMÉ Information Hub, all data will support regulatory frameworks and future research. The project's outcomes - harmonization and pre-standardization proposals - will contribute to a unified European assessment framework, reinforcing the continent's leadership in safe and sustainable materials innovation.