Identification of the safe(r) by design alternatives for nanosilver-enabled wound dressings.

The use of silver nanoparticles (NPs) in medical devices is constantly increasing due to their excellent antimicrobial properties. In wound dressings, Ag NPs are commonly added in large excess to exert a long-term and constant antimicrobial effect, provoking an instantaneous release of Ag ions during their use or the persistence of unused NPs in the wound dressing that can cause a release of Ag during the end-of-life of the product. For this reason, a Safe-by-Design procedure has been developed to reduce potential environmental risks while optimizing functionality and costs of wound dressings containing Ag NPs. The SbD procedure is based on ad-hoc criteria (e.g., mechanical strength, antibacterial effect, leaching of Ag from the product immersed in environmental media) and permits to identify the best one among five pre-market alternatives. A ranking of the SbD alternatives was obtained and the safer solution was selected based on the selected SbD criteria. The SbD framework was also applied to commercial wound dressings to compare the SbD alternatives with products already on the market. The iterative procedure permitted to exclude one of the alternatives (based on its low mechanical strength) and proved to be an effective approach that can be replicated to support the ranking, prioritisation, and selection of the most promising options early in the innovation process of nano-enabled medical devices as well as to encourage the production of medical devices safer for the environment.

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.

Chlorella vulgaris meets TiO2 NPs: Effective sorbent/photocatalytic hybrid materials for water treatment application.

A new class of bio-nano hybrid catalyst useable in downstream wastewater treatment was developed. We combined the sorption potentialities of Chlorella vulgaris microalgae with the photocatalytic properties of TiO2 NPs in order to investigate unexplored synergistic effects that could push the algal remediation technology toward a more promising cost-effective balance. We exploited non-living C. vulgaris, which keeps the biosorption properties of the living microalgae, but greatly enhancing the overall processability. C. vulgaris biomass was coupled with TiO2 NPs and the nanosols were then dried by means of a spray freeze drying (SFD) process able to produce highly reactive granules. A widespread physicochemical characterization supported the preparation and the performance evaluation, so highlighting the key-role of C. vulgaris/TiO2 interaction at the colloidal state. Heavy metal adsorption, tested for copper ions, and photocatalytic activity, assessed for Rhodamine B (RhB) photodegradation, were evaluated as key performances. The results pointed out a positive synergistic effect for hybrid samples consistent with the enhancement of metal biosorption which ranges from 103 mg g-1, for pristine C. vulgaris, to about 4000 mg g-1, when the biomass was coupled with the inorganic nanophase. The photocatalytic activity was well preserved with a complete RhB conversion after 1 h and even advanced in presence of SiO2NPs into the inorganic counterpart, so increasing the kinetic constant from 8.70 to 10.7 10-2 min-1. The results pave the way for the integration of these sorbent/photocatalytic hybrid materials into water remediation systems in an innovative sustainable design perspective.

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

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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.

Central role of dendritic cells in the regulation and deregulation of immune responses.

Dendritic cells (DCs) play a critical role in orchestrating the innate and adaptive components of the immune system so that appropriate, coordinated responses are mounted against infectious agents. Tissue-resident DCs interact with microbes through germline-encoded pattern-recognition receptors (PRRs), which recognize molecular patterns expressed by various microorganisms. Antigens use PRR activation to instruct DCs for the appropriate priming of natural killer (NK) cells, followed by specific T-cell responses. Due to the central role of DCs in regulating the activation and progression of immune responses, minor imbalances in the feedback control of Toll-like receptor (TLR)-activated cells have been associated with autoimmunity in genetically prone individuals. We review here recent findings on the role of DCs in the priming of innate and adaptive immune responses and the possible involvement of DCs in inducing and maintaining autoimmune reactions.