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      3D-printed graphene polylactic acid devices resistant to SARS-CoV-2: Sunlight-mediated sterilization of additive manufactured objects

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          Abstract

          Additive manufacturing has played a crucial role in the COVID-19 global emergency allowing for rapid production of medical devices, indispensable tools for hospitals, or personal protection equipment. However, medical devices, especially in nosocomial environments, represent high touch surfaces prone to viral infection and currently used filaments for 3D printing can't inhibit transmission of virus [1].

          Graphene-family materials are capable of reinforcing mechanical, optical and thermal properties of 3D printed constructs. In particular, graphene can adsorb near-infrared light with high efficiency. Here we demonstrate that the addition of graphene nanoplatelets to PLA filaments (PLA-G) allows the creation of 3D-printed devices that can be sterilized by near-infrared light exposure at power density analog to sunlight. This method has been used to kill SARS-CoV-2 viral particles on the surface of 3D printed PLA-G by 3 min of exposure. 3D-printed PLA-G is highly biocompatible and can represent the ideal material for the production of sterilizable personal protective equipment and daily life objects intended for multiple users.

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          De Maio Flavio: Study design, experimental Formal analysis, Writing – original draft, statistical analysis, Enrico Rosa: experiments and experimental Formal analysis, figures, Giordano Perini: experiments and experimental Formal analysis, figures, Alberto Augello: experiments and experimental Formal analysis, figures, Benedetta Niccolini: experiments and experimental Formal analysis, figures, Francesca Ciaiola, Giulia Santarelli: experiments and experimental Formal analysis, figures, Francesca Sciandra: experiments and experimental Formal analysis, figures, Manuela Bozzi: experiments and experimental Formal analysis, figures, Maurizio Sanguinetti: Resources, administration, Michela Sali: Resources, administration, Marco De Spirito: Resources, administration, Giovanni Delogu: data interpretation, writing, project coordination, Valentina Palmieri: data interpretation, writing, project coordination, Massimiliano Papi: data interpretation, writing, project coordination

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          Most cited references44

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          Stability of SARS-CoV-2 in different environmental conditions

          We previously reported the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in different clinical samples. 1 This virus can be detected on different surfaces in a contaminated site. 2 Here, we report the stability of SARS-CoV-2 in different environmental conditions. We first measured the stability of SARS-CoV-2 at different temperatures. SARS-CoV-2 in virus transport medium (final concentration ∼6·8 log unit of 50% tissue culture infectious dose [TCID50] per mL) was incubated for up to 14 days and then tested for its infectivity (appendix p 1). The virus is highly stable at 4°C, but sensitive to heat. At 4°C, there was only around a 0·7 log-unit reduction of infectious titre on day 14. With the incubation temperature increased to 70°C, the time for virus inactivation was reduced to 5 mins. We further investigated the stability of this virus on different surfaces. Briefly, a 5 μL droplet of virus culture (∼7·8 log unit of TCID50 per mL) was pipetted on a surface (appendix p 1; ∼cm2 per piece) and left at room temperature (22°C) with a relative humidity of around 65%. The inoculated objects retrieved at desired time-points were immediately soaked with 200 μL of virus transport medium for 30 mins to elute the virus. Therefore, this recovery of virus does not necessarily reflect the potential to pick up the virus from casual contact. No infectious virus could be recovered from printing and tissue papers after a 3-hour incubation, whereas no infectious virus could be detected from treated wood and cloth on day 2. By contrast, SARS-CoV-2 was more stable on smooth surfaces. No infectious virus could be detected from treated smooth surfaces on day 4 (glass and banknote) or day 7 (stainless steel and plastic). Strikingly, a detectable level of infectious virus could still be present on the outer layer of a surgical mask on day 7 (∼0·1% of the original inoculum). Interestingly, a biphasic decay of infectious SARS-CoV-2 could be found in samples recovered from these smooth surfaces (appendix pp 2–7). 39 representative non-infectious samples tested positive by RT-PCR 3 (data not shown), showing that non-infectious viruses could still be recovered by the eluents. We also tested the virucidal effects of disinfectants by adding 15 μL of SARS-CoV-2 culture (∼7·8 log unit of TCID50 per mL) to 135 μL of various disinfectants at working concentration (appendix p 1). With the exception of a 5-min incubation with hand soap, no infectious virus could be detected after a 5-min incubation at room temperature (22°C). Additionally, we also found that SARS-CoV-2 is extremely stable in a wide range of pH values at room temperature (pH 3–10; appendix p 1). Overall, SARS-CoV-2 can be highly stable in a favourable environment, 4 but it is also susceptible to standard disinfection methods.
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            Rational use of face masks in the COVID-19 pandemic

            Since the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that caused coronavirus disease 2019 (COVID-19), the use of face masks has become ubiquitous in China and other Asian countries such as South Korea and Japan. Some provinces and municipalities in China have enforced compulsory face mask policies in public areas; however, China's national guideline has adopted a risk-based approach in offering recommendations for using face masks among health-care workers and the general public. We compared face mask use recommendations by different health authorities (panel ). Despite the consistency in the recommendation that symptomatic individuals and those in health-care settings should use face masks, discrepancies were observed in the general public and community settings.1, 2, 3, 4, 5, 6, 7, 8 For example, the US Surgeon General advised against buying masks for use by healthy people. One important reason to discourage widespread use of face masks is to preserve limited supplies for professional use in health-care settings. Universal face mask use in the community has also been discouraged with the argument that face masks provide no effective protection against coronavirus infection. Panel Recommendations on face mask use in community settings WHO 1 • If you are healthy, you only need to wear a mask if you are taking care of a person with suspected SARS-CoV-2 infection. China 2 • People at moderate risk* of infection: surgical or disposable mask for medical use. • People at low risk† of infection: disposable mask for medical use. • People at very low risk‡ of infection: do not have to wear a mask or can wear non-medical mask (such as cloth mask). Hong Kong 3 • Surgical masks can prevent transmission of respiratory viruses from people who are ill. It is essential for people who are symptomatic (even if they have mild symptoms) to wear a surgical mask. • Wear a surgical mask when taking public transport or staying in crowded places. It is important to wear a mask properly and practice good hand hygiene before wearing and after removing a mask. Singapore 4 • Wear a mask if you have respiratory symptoms, such as a cough or runny nose. Japan 5 • The effectiveness of wearing a face mask to protect yourself from contracting viruses is thought to be limited. If you wear a face mask in confined, badly ventilated spaces, it might help avoid catching droplets emitted from others but if you are in an open-air environment, the use of face mask is not very efficient. USA 6 • Centers for Disease Control and Prevention does not recommend that people who are well wear a face mask (including respirators) to protect themselves from respiratory diseases, including COVID-19. • US Surgeon General urged people on Twitter to stop buying face masks. UK 7 • Face masks play a very important role in places such as hospitals, but there is very little evidence of widespread benefit for members of the public. Germany 8 • There is not enough evidence to prove that wearing a surgical mask significantly reduces a healthy person's risk of becoming infected while wearing it. According to WHO, wearing a mask in situations where it is not recommended to do so can create a false sense of security because it might lead to neglecting fundamental hygiene measures, such as proper hand hygiene. However, there is an essential distinction between absence of evidence and evidence of absence. Evidence that face masks can provide effective protection against respiratory infections in the community is scarce, as acknowledged in recommendations from the UK and Germany.7, 8 However, face masks are widely used by medical workers as part of droplet precautions when caring for patients with respiratory infections. It would be reasonable to suggest vulnerable individuals avoid crowded areas and use surgical face masks rationally when exposed to high-risk areas. As evidence suggests COVID-19 could be transmitted before symptom onset, community transmission might be reduced if everyone, including people who have been infected but are asymptomatic and contagious, wear face masks. Recommendations on face masks vary across countries and we have seen that the use of masks increases substantially once local epidemics begin, including the use of N95 respirators (without any other protective equipment) in community settings. This increase in use of face masks by the general public exacerbates the global supply shortage of face masks, with prices soaring, 9 and risks supply constraints to frontline health-care professionals. As a response, a few countries (eg, Germany and South Korea) banned exportation of face masks to prioritise local demand. 10 WHO called for a 40% increase in the production of protective equipment, including face masks. 9 Meanwhile, health authorities should optimise face mask distribution to prioritise the needs of frontline health-care workers and the most vulnerable populations in communities who are more susceptible to infection and mortality if infected, including older adults (particularly those older than 65 years) and people with underlying health conditions. People in some regions (eg, Thailand, China, and Japan) opted for makeshift alternatives or repeated usage of disposable surgical masks. Notably, improper use of face masks, such as not changing disposable masks, could jeopardise the protective effect and even increase the risk of infection. Consideration should also be given to variations in societal and cultural paradigms of mask usage. The contrast between face mask use as hygienic practice (ie, in many Asian countries) or as something only people who are unwell do (ie, in European and North American countries) has induced stigmatisation and racial aggravations, for which further public education is needed. One advantage of universal use of face masks is that it prevents discrimination of individuals who wear masks when unwell because everybody is wearing a mask. It is time for governments and public health agencies to make rational recommendations on appropriate face mask use to complement their recommendations on other preventive measures, such as hand hygiene. WHO currently recommends that people should wear face masks if they have respiratory symptoms or if they are caring for somebody with symptoms. Perhaps it would also be rational to recommend that people in quarantine wear face masks if they need to leave home for any reason, to prevent potential asymptomatic or presymptomatic transmission. In addition, vulnerable populations, such as older adults and those with underlying medical conditions, should wear face masks if available. Universal use of face masks could be considered if supplies permit. In parallel, urgent research on the duration of protection of face masks, the measures to prolong life of disposable masks, and the invention on reusable masks should be encouraged. Taiwan had the foresight to create a large stockpile of face masks; other countries or regions might now consider this as part of future pandemic plans. © 2020 Sputnik/Science Photo Library 2020 Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
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              Toward Nanotechnology-Enabled Approaches against the COVID-19 Pandemic

              The COVID-19 outbreak has fueled a global demand for effective diagnosis and treatment as well as mitigation of the spread of infection, all through large-scale approaches such as specific alternative antiviral methods and classical disinfection protocols. Based on an abundance of engineered materials identifiable by their useful physicochemical properties through versatile chemical functionalization, nanotechnology offers a number of approaches to cope with this emergency. Here, through a multidisciplinary Perspective encompassing diverse fields such as virology, biology, medicine, engineering, chemistry, materials science, and computational science, we outline how nanotechnology-based strategies can support the fight against COVID-19, as well as infectious diseases in general, including future pandemics. Considering what we know so far about the life cycle of the virus, we envision key steps where nanotechnology could counter the disease. First, nanoparticles (NPs) can offer alternative methods to classical disinfection protocols used in healthcare settings, thanks to their intrinsic antipathogenic properties and/or their ability to inactivate viruses, bacteria, fungi, or yeasts either photothermally or via photocatalysis-induced reactive oxygen species (ROS) generation. Nanotechnology tools to inactivate SARS-CoV-2 in patients could also be explored. In this case, nanomaterials could be used to deliver drugs to the pulmonary system to inhibit interaction between angiotensin-converting enzyme 2 (ACE2) receptors and viral S protein. Moreover, the concept of “nanoimmunity by design” can help us to design materials for immune modulation, either stimulating or suppressing the immune response, which would find applications in the context of vaccine development for SARS-CoV-2 or in counteracting the cytokine storm, respectively. In addition to disease prevention and therapeutic potential, nanotechnology has important roles in diagnostics, with potential to support the development of simple, fast, and cost-effective nanotechnology-based assays to monitor the presence of SARS-CoV-2 and related biomarkers. In summary, nanotechnology is critical in counteracting COVID-19 and will be vital when preparing for future pandemics.
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                Author and article information

                Journal
                Carbon N Y
                Carbon N Y
                Carbon
                Published by Elsevier Ltd.
                0008-6223
                0008-6223
                16 March 2022
                16 March 2022
                Affiliations
                [a ]Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario “A. Gemelli” IRCSS, Largo A. Gemelli, 8 00168, Rome, Italy
                [b ]Dipartimento di Scienze biotecnologiche di base, cliniche intensivologiche e perioperatorie – Sezione di Microbiologia, Università Cattolica del Sacro Cuore, Rome, Largo Francesco Vito 1, 00168, Italy
                [c ]Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, Largo Francesco Vito 1, 00168, Italy
                [d ]Fondazione Policlinico Universitario “A. Gemelli” IRCSS, Largo A. Gemelli, 8 00168, Rome, Italy
                [e ]Istituto di Scienze e Tecnologie Chimiche “Giulio Natta”, (SCITEC)-CNR, SS Roma, Italy
                [f ]Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Sezione di Biochimica e Biochimica Clinica, Università Cattolica del Sacro Cuore, Rome, Italy
                [g ]Mater Olbia Hospital, Olbia, Italy
                [h ]Istituto dei Sistemi Complessi, CNR, Via dei Taurini 19, 00185, Rome, Italy
                Author notes
                []Corresponding author. Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, Largo Francesco Vito 1, 00168, Italy.
                [∗∗ ]Corresponding author. Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, Largo Francesco Vito 1, 00168, Italy.
                [1]

                Co-first authors.

                Article
                S0008-6223(22)00208-1
                10.1016/j.carbon.2022.03.036
                8926154
                35313599
                8c9a9470-1437-4625-aab0-56a940b2b060
                © 2022 Published by Elsevier Ltd.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 1 January 2022
                : 21 February 2022
                : 14 March 2022
                Categories
                Article

                graphene,scaffolds,sars-cov-2 inhibition,nanotechnology,nir light sterilization

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