The Safe-by-Design concept (SbD) incorporates safety of nano-enabled product (NEP) at the design stage of the production process. SbD reverses the paradigm of downstream risk analysis and management (‘is it safe?’, ‘can it be controlled?’, ‘does it transform?’) and pursues the production of less hazardous nano-products affording reduced exposure, mediated by the release of nanomaterials during the life-cycle. The SbD production of NEPs has been recently elaborated upon, and several EU funded projects have provided some tools, databases, and case studies for its implementation.

Despite the advantages that can be obtained, the current state of the art indicates that industrial production is struggling to activate the SbD approach and the fast industrial uptake of engineered nanomaterials (NMs) is missing or unsafely implemented. The delay of nanomanufacturing implementation in the industry is due to incorrect use, lack of NMs culture, and/or difficult access to better quality NMs due to cost or logistics reasons. Psychological difficulties due to the use of unregulated substances, easy access to non-quality-certified NMs, difficulties in following the fast technological evolution of NMs also play a role.

ASINA aims to:

  • support the fast industrial uptake of nanotechnology by providing Safe-by-Design solutions and supporting tools;
  • to give entrepreneurs knowledge and awareness of Safe-by-Design potential;
  • to increase confidence in Safe-by-Design nanomanufacturing by improving the interaction and integration of different stakeholders (entrepreneurs, scientists, regulators, innovators, policy makers).

For this purpose, the proposal will take into consideration the important nano design features of coating and encapsulation and related Value Chains (VCs). ASINA will develop a specific Safe-by-Design Management Methodology, consistent with modern business management systems, to deliver Safe-by-Design solutions and inform design decisions. The project will establish a pilot action, involving test beds and pilot plants, for testing and validating the methodology contents as specific implementations that can be generalized to other engineered nanomaterials, nano-enabled products and industrial case studies. ASINA will finally export the methodology to the industry through a roadmap (including guidelines, analytical tools, best practices) and other standardization deliverables such as CEN-CWA, as a realistic way to ensure diffusion of the ASINA SMM and its industrial implementation worldwide.


  • PROJECT TITLE: Anticipating Safety Issues at the Design Stage of NAno Product Development
  • START DATE: 01 March 2020
  • END DATE: 28 February 2024
  • TOPIC: NMBP-15-2019
    Safe by design, from science to regulation: metrics and main sectors (RIA)
  • EU CONTRIBUTION: 5,998,386.06 euro

Project Coordinator: Anna Luisa Costa

Partner UNIMIB – POLARIS: Paride Mantecca WP2 leader

This project has received funding from the European Union’s Horizon 2020 research and innovation programme (grant agreement: 862444).

Read more:

ASINA Web site



The Safe and Sustainable by Design (SSbD) framework aims to steer the innovation process towards the green and sustainable industrial transition, substitute or minimise the production and use of substances of concern, and minimise the impact on health, climate and the environment during sourcing, production, use and end-of-life of chemicals, materials and products. However, SSbD implementation to nanomaterials (NMs) is hampered by a lack of harmonized or specific data and datasets which poses a challenge to the design of safe and sustainable NMs and their incorporation into nano-enabled products (NEPs).

INTEGRANO aims to:

• Support decision making in NM development, enabling stakeholders (scientists, material engineers, policymakers) to tackle the SSbD challenge in the NM context

• Promote the design and redesign of NMs and NEPs by reducing R&D and approval lead time, minimising costs and increasing data transparency

• To support industry by reducing research and technological development and innovation risk related to safety and sustainability by enabling impact-based informed investment decisions

UNIMIB is project coordinator of the project and leader of WP3, which aims at nano-tox and nano eco-tox data generation.


Grant Agreement: 101138414

Project Coordinator: Paride Mantecca (UNIMIB)

UNIMIB WP leader: Maurizio Gualtieri (WP3 Leader)

More information here

Scientific Publications 2024

  • Saibene M, Serchi T, Bonfanti P, Colombo A, Nelissen I, Halder R, Audinot JN, Pelaz B, Soliman MG, Parak WJ, Mantecca P, Gutleb AC, Cambier S. The use of a complex tetra-culture alveolar model to study the biological effects induced by gold nanoparticles with different physicochemical properties. Environ Toxicol Pharmacol. 2024 Mar:106:104353. DOI: 10.1016/j.etap.2023.104353
  • Perelshtein I, Shoshani S, Jacobi G, Natan M,  Dudchenko N, Perkas N, Tkachev M, Bengalli R, Fiandra L, Mantecca P, Ivanova K, Tzanov T, Banin E, Gedanken AProtecting the Antibacterial Coating of Urinal Catheters for Improving Safety. ACS Appl Bio Mater2024 Feb 19;7(2):990-998. DOI: 10.1021/acsabm.3c00988
  • Motta G, Gualtieri M, Bengalli R, Saibene M, Belosi F, Nicosia A, Cabellos J, Mantecca P. An integrated new approach methodology for inhalation risk assessment of safe and sustainable by design nanomaterials. Environ Int. 2024 Jan:183:108420. DOI: 10.1016/j.envint.2024.108420



UNIMIB is coordinator of a new Horizon Europe project: INTEGRANO (GA. 101138414).

In line with the current guidelines for Safe and Sustainable by Design – SSbD chemicals and materials, INTEGRANO proposes a general assessment approach based on quantitative evidence to be applied in practice for specific Nano Materials (NMs) design cases.
INTEGRANO ambition is to set the basis for a new paradigm based on standardised frameworks and by creating suitable NMs datasets as well as Nanospecific impact categories of NMs through their Life Cycle Stages (LCS), applied to specific design cases assessment.

12 partners from 8 different countries participate in the hashtagIntegrano Project. This network allows for different expertises and skills within the project, which complement and support each other.

For further information visit INTEGRANO page, the website INTEGRANO – INTEGRANO or the Linkedin page.

Scientific Publications 2023

  • Bengalli RD, Zerbi G, Lucotti A, Catelani T, Mantecca P. Carbon nanotubes: Structural defects as stressors inducing lung cell toxicity. Chem Biol Interact. 2023 Sep 1;382:110613.
  • Botto L, Lonati E, Russo S, Cazzaniga E, Bulbarelli A, Palestini P. Effects of PM2.5 Exposure on the ACE/ACE2 Pathway: Possible Implication in COVID-19 Pandemic. Int J Environ Res Public Health. 2023 Mar 1;20(5):4393.
  • Bragato C, Pistocchi A, Bellipanni G, Confalonieri S, Balciunie J, Monastra FM, Carra S, Vitale G, Mantecca P, Cotelli F, Gaudenzi G. Zebrafish dnm1a gene plays a role in the formation of axons and synapses in the nervous tissue. J Neurosci Res. 2023 Apr 9.
  • Gualtieri M, Carriere M, Mantecca P. Hazard, Distribution and Exposure of Particulate Pollution from Indoor and Outdoor Environments.Toxics. 2023 Sep 12;11(9):772.
  • Kose O, Béal D, Motellier S, Pelissier N, Collin-Faure V, Blosi M, Bengalli R, Costa A, Furxhi I, Mantecca P, Carriere M. Physicochemical Transformations of Silver Nanoparticles in the Oro-Gastrointestinal Tract Mildly Affect Their Toxicity to Intestinal Cells In Vitro: An AOP-Oriented Testing Approach. Toxics. 2023; 11(3):199.
  • Kose O, Mantecca P, Costa A, Carrière M. Putative adverse outcome pathways for silver nanoparticle toxicity on mammalian male reproductive system: a literature review. Part Fibre Toxicol. 2023 Jan 5;20(1):1.
  • Marchetti S., Gualtieri M., Pozzer A, Lelieveld J., Hansell A. L., Colombo A., Mantecca P. On fine particulate matter and COVID-19 spread and severity: an in vitro toxicological plausible mechanism. Environ Int. 179 (2023) 108131.
  • Moschini E, Colombo G, Chirico G, Capitani G, Dalle-Donne I, Mantecca P. Biological mechanism of cell oxidative stress and death during short-term exposure to nano CuO. Sci Rep. 2023 Feb 9;13(1):2326.
  • Motta G, Gualtieri M, Saibene M, Bengalli R, Brigliadori A, Carrière M, Mantecca P. Preliminary Toxicological Analysis in a Safe-by-Design and Adverse Outcome Pathway-Driven Approach on Different Silver Nanoparticles: Assessment of Acute Responses in A549 Cells. Toxics. 2023; 11(2):195.


BIOMAT – Open  Innovation Test Bed for Nano-Enabled Bio-Based PUR Foams and composites

The POLARIS Research Center is involved in the European BIOMAT project, funded by the European Commission in the Horizon 2020 framework (Grant Agreement nr.) with the aim of establishing an Open Innovation Test Bed (BIOMAT-TB) with a Single-Entry Point (SEP) . The aim of this project is to accelerate a sustainable European bioeconomy through the development of nanomaterial-based and advanced polyurethane foams (PUR Foams) for various companies (building, construction, automotive, furniture, textiles).

Project ID:953270; Call ID: H2020-EU.2.1.3. – INDUSTRIAL LEADERSHIP – Leadership in enabling and industrial technologies – Advanced materials;   H2020-EU.2.1.2. – INDUSTRIAL LEADERSHIP – Leadership in enabling and industrial technologies – Nanotechnologies

Project coordinator: Dr. Mariana Ornelas (CENTI)

Dissemination Manager: Dr. Pnina Dan (OSM-DAN LTD).

Partner UNIMIB – POLARIS Prof. Paride Mantecca is leader of WP7 – Recycling technologies, nanosafety and regulatory issues with specific focus on Nanosafety and toxicology (Task 7.2).

Further information can be found at the link.



Antibiotics, pathogens and antimicrobial resistant (AMR) bacteria are contaminants of emerging concern (CECs) in water bodies associated to intensive fish and inland animal farming.  AMROCE aims at reducing antibiotic pollution and spread of AMR bacteria in the entire water cycle through a platform of novel antibiotic-free antimicrobial products. In the project, antimicrobial/antibiofilm fish cage nets and wastewater filtration membranes will be developed through polymer and surface nano-engineering. Marine-derived antimicrobial agents and antibiofilm enzymes will be nano-formulated as alternative to antibiotics for fish and animal feed supplement. Human and environmental nanosafety during the manufacturing and use of the novel nanotechnology-embedded products will be continuously evaluated to anticipate nanosafety issues.

UNIMIB is leader of WP3, which aims at identifying the parameters related to the safety of the nano-formulation process for both workers and users, considering not only the existing regulation, but also the gaps existing in the legislation and norms.

Project Coordinator: Tzanko Tzanov (UPC)

UNIMIB WP/Task leader: Paride Mantecca (WP3)

Please visit the webiste of the project