Occupational risk of nano-biomaterials: Assessment of nano-enabled magnetite contrast agent using the BIORIMA Decision Support System.

The assessment of the safety of nano-biomedical products for patients is an essential prerequisite for their market authorization. However, it is also required to ensure the safety of the workers who may be unintentionally exposed to the nano-biomaterials (NBMs) in these medical applications during their synthesis, formulation into products and end-of-life processing and also of the medical professionals (e.g., nurses, doctors, dentists) using the products for treating patients. There is only a handful of workplace risk assessments focussing on NBMs used in medical applications. Our goal is to contribute to increasing the knowledge in this area by assessing the occupational risks of magnetite (Fe3O4) nanoparticles coated with PLGA-b-PEG-COOH used as contrast agent in magnetic resonance imaging (MRI) by applying the software-based Decision Support System (DSS) which was developed in the EU H2020 project BIORIMA. The occupational risk assessment was performed according to regulatory requirements and using state-of-the-art models for hazard and exposure assessment, which are part of the DSS. Exposure scenarios for each life cycle stage were developed using data from literature, inputs from partnering industries and results of a questionnaire distributed to healthcare professionals, i.e., physicians, nurses, technicians working with contrast agents for MRI. Exposure concentrations were obtained either from predictive exposure models or monitoring campaigns designed specifically for this study. Derived No-Effect Levels (DNELs) were calculated by means of the APROBA tool starting from in vivo hazard data from literature. The exposure estimates/measurements and the DNELs were used to perform probabilistic risk characterisation for the formulated exposure scenarios, including uncertainty analysis. The obtained results revealed negligible risks for workers along the life cycle of magnetite NBMs used as contrast agent for the diagnosis of tumour cells in all exposure scenarios except in one when risk is considered acceptable after the adoption of specific risk management measures. The study also demonstrated the added value of using the BIORIMA DSS for quantification and communication of occupational risks of nano-biomedical applications and the associated uncertainties.

µMAPPS: a novel phasor approach to second harmonic analysis for in vitro-in vivo investigation of collagen microstructure.

Second Harmonic Generation (SHG) is a label-free imaging method used to monitor collagen organization in tissues. Due to its sensitivity to the incident polarization, it provides microstructural information otherwise unreachable by other intensity based imaging methods. We develop and test a Microscopic Multiparametric Analysis by Phasor projection of Polarization-dependent SHG (µMAPPS) that maps the features of the collagen architecture in tissues at the micrometer scale. µMAPPS retrieves pixel-by-pixel the collagen fibrils anisotropy and orientation by operating directly on two coupled phasor spaces, avoiding direct fitting of the polarization dependent SHG signal. We apply µMAPPS to fixed tissue sections and to the study of the collagen microscopic organization in tumors ex-vivo and in-vivo. We develop a clustering algorithm to automatically group pixels with similar microstructural features. µMAPPS can perform fast analyses of tissues and opens to future applications for in-situ diagnosis of pathologies and diseases that could assist histo-pathological evaluation.