{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T12:28:43Z","timestamp":1766579323638,"version":"build-2065373602"},"reference-count":60,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["EBJ"],"abstract":"<jats:p>Thorough biological safety testing of topical therapeutic compounds and antimicrobials is a critical prerequisite for appropriate cutaneous wound care. Increasing pathogen resistance rates to traditional antibiotics and antifungals are driving the development and registration of novel chemical entities. Although they are notably useful for animal testing reduction, the gold standard in vitro cytotoxicity assays in continuous cell lines (HaCaT keratinocytes, 3T3 fibroblasts) may be discussed from a translational relevance standpoint. The aim of this study was thus to establish and validate a sustainable primary cell banking model with a view to performing optimized in vitro cytotoxicity assay development. Primary dermal fibroblasts and adipose-derived stem cell (ASC) types were established from four infant polydactyly sources. A multi-tiered primary cell banking model was then applied to prepare highly sustainable and standardized dermal fibroblast and ASC working cell banks (WCBs), potentially allowing for millions of biological assays to be performed. The obtained cellular materials were then validated for use in cytotoxicity assays through in vitro biosafety testing of topical antiseptics (chlorhexidine, hypochlorous acid) and an antifungal compound (AR-12) of interest for optimized burn wound care. The experimental results confirmed that IC50 values were comparable between cytotoxicity assays, which were performed with cell lines and with primary cells. The results also showed that hypochlorous acid (HOCl) displayed an enhanced toxicological profile as compared to the gold standard chlorhexidine (CLX). Generally, this study demonstrated that highly sustainable primary cell sources may be established and applied for consistent topical compound biological safety assessments with enhanced translational relevance. Overall, the study underscored the safety-oriented interest of functionally benchmarking the products that are applied on burn patient wounds for the global enhancement of burn care quality.<\/jats:p>","DOI":"10.3390\/ebj5030024","type":"journal-article","created":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T11:54:19Z","timestamp":1722945259000},"page":"249-270","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Sustainable Primary Cell Banking for Topical Compound Cytotoxicity Assays: Protocol Validation on Novel Biocides and Antifungals for Optimized Burn Wound Care"],"prefix":"10.3390","volume":"5","author":[{"given":"Zhifeng","family":"Liao","sequence":"first","affiliation":[{"name":"Plastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas","family":"Laurent","sequence":"additional","affiliation":[{"name":"Plastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1220-0213","authenticated-orcid":false,"given":"Nathalie","family":"Hirt-Burri","sequence":"additional","affiliation":[{"name":"Plastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland"},{"name":"Lausanne Burn Center, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corinne","family":"Scaletta","sequence":"additional","affiliation":[{"name":"Plastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland"},{"name":"Lausanne Burn Center, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6054-0573","authenticated-orcid":false,"given":"Philippe","family":"Abdel-Sayed","sequence":"additional","affiliation":[{"name":"Plastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland"},{"name":"Lausanne Burn Center, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland"},{"name":"STI School of Engineering, Federal Polytechnical School of Lausanne, CH-1015 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wassim","family":"Raffoul","sequence":"additional","affiliation":[{"name":"Plastic and Reconstructive Surgery, Ensemble Hospitalier de la C\u00f4te, CH-1110 Morges, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5123-1656","authenticated-orcid":false,"given":"Shengkang","family":"Luo","sequence":"additional","affiliation":[{"name":"Plastic and Reconstructive Surgery, Guangdong Second Provential General Hospital, Guangzhou 510317, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Damian","family":"Krysan","sequence":"additional","affiliation":[{"name":"Stead Family Department of Pediatrics, Carver College of Medicine, Stead Family Children\u2019s Hospital, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5738-8702","authenticated-orcid":false,"given":"Alexis","family":"Laurent","sequence":"additional","affiliation":[{"name":"Plastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland"},{"name":"Manufacturing Department, TEC-PHARMA SA, CH-1038 Bercher, Switzerland"},{"name":"Manufacturing Department, LAM Biotechnologies SA, CH-1066 Epalinges, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7346-9921","authenticated-orcid":false,"given":"Lee","family":"Applegate","sequence":"additional","affiliation":[{"name":"Plastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland"},{"name":"Lausanne Burn Center, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland"},{"name":"Center for Applied Biotechnology and Molecular Medicine, University of Zurich, CH-8057 Zurich, Switzerland"},{"name":"Oxford OSCAR Suzhou Center, Oxford University, Suzhou 215123, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1089\/sur.2020.299","article-title":"Fungal infections in burn patients","volume":"22","author":"Palackic","year":"2021","journal-title":"Surg. Inf."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1089\/sur.2013.134","article-title":"Infection in burns","volume":"17","author":"Norbury","year":"2016","journal-title":"Surg. Inf."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1093\/jbcr\/irad168","article-title":"Understanding the drivers of cost and length of stay in a cohort of 21,875 patients with severe burn","volume":"45","author":"Hauc","year":"2024","journal-title":"J. Burn Care Res."},{"key":"ref_4","first-page":"198","article-title":"Antiseptics for burns: A review of the evidence","volume":"31","author":"Slaviero","year":"2018","journal-title":"Ann. Burns Fire Dis."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Hemmati, J., Azizi, M., Asghari, B., and Arabestani, M.R. (2023). Multidrug-resistant pathogens in burn wound, prevention, diagnosis, and therapeutic approaches (conventional antimicrobials and nanoparticles). Can. J. Infect. Dis. Med. Microbiol., 2023.","DOI":"10.1155\/2023\/8854311"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ortega-Llamas, L., Qui\u00f1ones-Vico, M.I., Garc\u00eda-Valdivia, M., Fern\u00e1ndez-Gonz\u00e1lez, A., Ubago-Rodr\u00edguez, A., Sanabria-de la Torre, R., and Arias-Santiago, S. (2022). Cytotoxicity and wound closure evaluation in skin cell lines after treatment with common antiseptics for clinical use. Cells, 11.","DOI":"10.3390\/cells11091395"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1111\/ced.15235","article-title":"Effect of the most common wound antiseptics on human skin fibroblasts","volume":"47","author":"Ruiz","year":"2022","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1016\/j.burns.2019.12.008","article-title":"Implications of chlorhexidine use in burn units for wound healing","volume":"46","author":"Tornay","year":"2020","journal-title":"Burns"},{"key":"ref_9","unstructured":"International Wound Infection Institute (IWII) (2022). Wound Infection in Clinical Practice, Wounds International."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"536","DOI":"10.4103\/jcd.jcd_288_22","article-title":"Effectiveness of polyhexamethylene biguanide, chlorhexidine, and calcium hydroxide intracanal medicament against intraradicular mature polymicrobial biofilm: A microbiological study","volume":"25","author":"Khan","year":"2022","journal-title":"J. Conserv. Dent."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1111\/wrr.12994","article-title":"Chronic wounds: Treatment consensus","volume":"30","author":"Eriksson","year":"2022","journal-title":"Wound Rep. Regen."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1111\/jocd.13280","article-title":"Topical stabilized hypochlorous acid: The future gold standard for wound care and scar management in dermatologic and plastic surgery procedures","volume":"19","author":"Gold","year":"2020","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_13","first-page":"342","article-title":"Hypochlorous acid: An ideal wound care agent with powerful microbicidal, antibiofilm, and wound healing potency","volume":"26","author":"Sakarya","year":"2014","journal-title":"Wounds"},{"key":"ref_14","unstructured":"OECD (2010). Guidance Document on Using Cytotoxicity Tests to Estimate Starting doses for Acute Oral Systemic Toxicity Tests, No. 129, OECD."},{"key":"ref_15","unstructured":"OECD (2022). Guidance Document for the Testing of Chemicals: In Vitro Skin Sensitization, No. 442D, OECD."},{"key":"ref_16","unstructured":"(2022). Biological Evaluation of Medical Devices (Standard No. ISO 10993-5:2009)."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Garg, S., Huifu, H., Kaul, S.C., and Wadhwa, R. (2018). Integration of conventional cell viability assays for reliable and reproducible read-outs: Experimental evidence. BMC Res. Notes, 11.","DOI":"10.1186\/s13104-018-3512-5"},{"key":"ref_18","first-page":"146","article-title":"Comparison of primary human fibroblasts and keratinocytes with immortalized cell lines regarding their sensitivity to sodium dodecyl sulfate in a neutral red uptake cytotoxicity assay","volume":"59","author":"Schrader","year":"2009","journal-title":"Arzneimittelforschung"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1016\/j.yrtph.2015.09.015","article-title":"The use of human adipose-derived stem cells-based cytotoxicity assay for acute toxicity test","volume":"73","author":"Abud","year":"2015","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Wei, Z., Xu, T., Strickland, J., Zhang, L., Fang, Y., Tao, D., Simeonov, A., Huang, R., Kleinstreuer, N.C., and Xia, M. (2024). Use of in vitro methods combined with in silico analysis to identify potential skin sensitizers in the Tox21 10K compound library. Front. Toxicol., 6.","DOI":"10.3389\/ftox.2024.1321857"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kan\u010f\u00e1rov\u00e1, H., and P\u00f4bi\u0161, P. (2024). The \u201cBig Three\u201d in biocompatibility testing of medical devices: Implementation of alternatives to animal experimentation-are we there yet?. Front. Toxicol., 5.","DOI":"10.3389\/ftox.2023.1337468"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1111\/bcpt.12790","article-title":"Human BJ fibroblasts is an alternative to mouse BALB\/c 3T3 cells in in vitro neutral red uptake assay","volume":"121","author":"Toimela","year":"2017","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1515\/aut-2007-070307","article-title":"Evaluating the toxicity of reactive dyes and dyed fabrics with the HaCaT cytotoxicity test","volume":"7","author":"Klemola","year":"2007","journal-title":"Autex Res. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1007\/s10517-017-3785-z","article-title":"Sodium dodecyl sulfate cytotoxicity towards HaCaT keratinocytes: Comparative analysis of methods for evaluation of cell viability","volume":"163","author":"Rusanov","year":"2017","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.ijpharm.2017.01.024","article-title":"Insights on in vitro models for safety and toxicity assessment of cosmetic ingredients","volume":"519","author":"Almeida","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Zerbinati, N., Sommatis, S., Maccario, C., Di Francesco, S., Capillo, M.C., Grimaldi, G., Rauso, R., Herrera, M., Bencini, P.L., and Mocchi, R. (2021). A practical approach for the in vitro safety and efficacy assessment of an anti-ageing cosmetic cream enriched with functional compounds. Molecules, 26.","DOI":"10.3390\/molecules26247592"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"101515","DOI":"10.1016\/j.mex.2021.101515","article-title":"Using inhibition of the adipogenesis of adipose-derived stem cells in vitro for toxicity prediction","volume":"8","author":"Abud","year":"2021","journal-title":"MethodsX"},{"key":"ref_28","unstructured":"OECD (2005). Guidance Document on the Validation and International Acceptance of New or Updated Test Methods for Hazard Assessment, OECD."},{"key":"ref_29","first-page":"1","article-title":"Enhancement of human adipose-derived stem cell expansion and stability for clinical use","volume":"2","author":"Grognuz","year":"2015","journal-title":"Int. J. Stem Cell Res. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1042\/BCJ20170780","article-title":"Stem cell models as an in vitro model for predictive toxicology","volume":"476","author":"Lynch","year":"2019","journal-title":"Biochem. J."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Laurent, A., Abdel-Sayed, P., Hirt-Burri, N., Scaletta, C., Michetti, M., de Buys Roessingh, A., Raffoul, W., and Applegate, L.A. (2021). Evolution of diploid progenitor lung cell applications: From optimized biotechnological substrates to potential active pharmaceutical ingredients in respiratory tract regenerative medicine. Cells, 10.","DOI":"10.3390\/cells10102526"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Cavalli, E., Levinson, C., Hertl, M., Broguiere, N., Br\u00fcck, O., Mustjoki, S., Gerstenberg, A., Weber, D., Salzmann, G., and Steinwachs, M. (2019). Characterization of polydactyly chondrocytes and their use in cartilage engineering. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-40575-w"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s41232-017-0053-6","article-title":"Characterization of polydactyly-derived chondrocyte sheets versus adult chondrocyte sheets for articular cartilage repair","volume":"37","author":"Maehara","year":"2017","journal-title":"Inflamm. Regen."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1007\/s004030050461","article-title":"Tissue engineering with HaCaT cells and a fibroblast cell line","volume":"291","author":"Kehe","year":"1999","journal-title":"Arch. Dermatol. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1006\/excr.2002.5485","article-title":"Effects of establishing cell cultures and cell culture conditions on the proliferative life span of human fibroblasts isolated from different tissues and donors of different ages","volume":"274","author":"Balin","year":"2002","journal-title":"Exp. Cell Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.jhin.2009.12.010","article-title":"Residual effect of antiseptic substances on human skin","volume":"75","author":"Urban","year":"2010","journal-title":"J. Hosp. Inf."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"S49","DOI":"10.1016\/j.ajic.2012.10.030","article-title":"Reducing the risk of surgical site infections: Does chlorhexidine gluconate provide a risk reduction benefit?","volume":"41","author":"Edmiston","year":"2013","journal-title":"Am. J. Inf. Contr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1097\/DCC.0000000000000165","article-title":"The effect of chlorhexidine bathing on rates of nosocomial infections among the critically ill population: An analysis of current clinical research and recommendations for practice","volume":"35","author":"Raines","year":"2016","journal-title":"Dim. Crit. Care Nurs."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1093\/jac\/dky432","article-title":"Safety and efficacy profiles of different commercial sodium hypochlorite\/hypochlorous acid solutions (NaClO\/HClO): Antimicrobial efficacy, cytotoxic impact, and physicochemical parameters in vitro","volume":"74","author":"Severing","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1111\/iwj.12625","article-title":"In vitro microbicidal, anti-biofilm and cytotoxic effects of different commercial antiseptics","volume":"14","author":"Robson","year":"2017","journal-title":"Int. Wound J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"223","DOI":"10.4265\/bio.22.223","article-title":"Stability of weakly acidic hypochlorous acid solution with microbicidal activity","volume":"22","author":"Ishihara","year":"2017","journal-title":"Biocontrol. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1111\/ijd.16099","article-title":"The role of sodium hypochlorite in atopic dermatitis therapy: A narrative review","volume":"61","author":"Krynicka","year":"2022","journal-title":"Int. J. Derm."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1111\/pde.13842","article-title":"Sodium hypochlorite body wash in the management of Staphylococcus aureus-colonized moderate-to-severe atopic dermatitis in infants, children, and adolescents","volume":"36","author":"Majewski","year":"2019","journal-title":"Ped. Dermatol."},{"key":"ref_44","first-page":"CD005083","article-title":"Honey as a topical treatment for wounds","volume":"2015","author":"Jull","year":"2015","journal-title":"Cochrane Data Syst. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1016\/j.joms.2020.06.029","article-title":"Hypochlorous acid: A review","volume":"78","author":"Block","year":"2020","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"165","DOI":"10.4265\/jmc.28.4_165","article-title":"Uses of gaseous hypochlorous acid for controlling microorganisms in indoor spaces","volume":"28","author":"Fukuzaki","year":"2023","journal-title":"J. Microorg. Contr."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Tazawa, K., Jadhav, R., Azuma, M.M., Fenno, J.C., McDonald, N.J., and Sasaki, H. (2023). Hypochlorous acid inactivates oral pathogens and a SARS-CoV-2-surrogate. BMC Oral Health, 23.","DOI":"10.1186\/s12903-023-02820-7"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1007\/s00595-014-1050-x","article-title":"Efficacy and safety of strong acid electrolyzed water for peritoneal lavage to prevent surgical site infection in patients with perforated appendicitis","volume":"45","author":"Kubota","year":"2015","journal-title":"Surg. Today"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"448","DOI":"10.2166\/wh.2021.260","article-title":"Comparison of the SARS-CoV-2-inactivating activities of the differently manufactured hypochlorous acid water products with various pH","volume":"19","author":"Takeda","year":"2021","journal-title":"J. Water Health"},{"key":"ref_50","unstructured":"Briotech (2022). Instructions for Use of the Brio\u00ae Product, Briotech. unpublished work."},{"key":"ref_51","unstructured":"Urgo Medical (2022). Instructions for Use of the Vashe\u00ae Product, Urgo Medical. unpublished work."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1038\/nprot.2008.75","article-title":"Neutral red uptake assay for the estimation of cell viability\/cytotoxicity","volume":"3","author":"Repetto","year":"2008","journal-title":"Nat. Protoc."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1021\/acsinfecdis.5b00134","article-title":"Antitumor\/antifungal celecoxib derivative AR-12 is a non-nucleoside inhibitor of the ANL-family adenylating enzyme acetyl CoA synthetase","volume":"2","author":"Koselny","year":"2016","journal-title":"ACS Infect. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"7115","DOI":"10.1128\/AAC.01061-16","article-title":"The celecoxib derivative AR-12 has broad-spectrum antifungal activity in vitro and improves the activity of fluconazole in a murine model of cryptococcosis","volume":"60","author":"Koselny","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.chembiol.2019.10.012","article-title":"Metabolic modifier screen reveals secondary targets of protein kinase inhibitors within nucleotide metabolism","volume":"27","author":"Abt","year":"2020","journal-title":"Cell Chem. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Dolatyari, M., and Rostami, A. (2022). Strong anti-viral nano biocide based on Ag\/ZnO modified by amodiaquine as an antibacterial and antiviral composite. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-24540-8"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"161889","DOI":"10.1016\/j.scitotenv.2023.161889","article-title":"Application of silver-based biocides in face masks intended for general use requires regulatory control","volume":"870","author":"Mast","year":"2023","journal-title":"Sci. Tot. Environ."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"226","DOI":"10.4014\/jmb.1906.06070","article-title":"Biocidal activity of metal nanoparticles synthesized by Fusarium solani against multidrug-resistant bacteria and mycotoxigenic fungi","volume":"30","year":"2020","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1007\/s10534-021-00344-7","article-title":"Ecofriendly preparation of silver nanoparticles-based nanocomposite stabilized by polysaccharides with antibacterial, antifungal and antiviral activities","volume":"34","author":"Hasanin","year":"2021","journal-title":"Biometals"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"World Medical Association (2013). World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA, 310, 2191\u20132194.","DOI":"10.1001\/jama.2013.281053"}],"container-title":["European Burn Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2673-1991\/5\/3\/24\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:30:42Z","timestamp":1760110242000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2673-1991\/5\/3\/24"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,6]]},"references-count":60,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["ebj5030024"],"URL":"https:\/\/doi.org\/10.3390\/ebj5030024","relation":{},"ISSN":["2673-1991"],"issn-type":[{"type":"electronic","value":"2673-1991"}],"subject":[],"published":{"date-parts":[[2024,8,6]]}}}