materials Article Evaluation of Long–Lasting Antibacterial Properties and Cytotoxic Behavior of Functionalized Silver- Nanocellulose Composite Roberta Grazia Toro 1 , Abeer Mohamed Adel 2 , Tilde de Caro 1 , Fulvio Federici 1 , Luciana Cerri 1 , Eleonora Bolli 1 , Alessio Mezzi 1 , Marianna Barbalinardo 3 , Denis Gentili 3 , Massimiliano Cavallini 3 , Mona Tawfik Al-Shemy 2 , Roberta Montanari 4 and Daniela Caschera 1, *   Citation: Toro, R.G.; Adel, A.M.; de Caro, T.; Federici, F.; Cerri, L.; Bolli, E.; Mezzi, A.; Barbalinardo, M.; Gentili, D.; Cavallini, M.; et al. Evaluation of Long–Lasting Antibacterial Properties and Cytotoxic Behavior of Functionalized Silver-Nanocellulose Composite. Materials 2021, 14, 4198. https://doi.org/10.3390/ma14154198 Academic Editor: Andrzej Dziedzic Received: 14 June 2021 Accepted: 21 July 2021 Published: 27 July 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Institute for the Study of Nanostructured Materials, National Council of Research, Via Salaria km 29,300, Monterotondo, 00015 Rome, Italy; robertagrazia.toro@cnr.it (R.G.T.); tilde.decaro@cnr.it (T.d.C.); fulvio.federici@cnr.it (F.F.); luciana.cerri@cnr.it (L.C.); eleonora.bolli@ismn.cnr.it (E.B.); alessio.mezzi@cnr.it (A.M.) 2 Cellulose and Paper Department, National Research Centre, 33El-Bohouth St. (Former El-Tahrir St.), Dokki, Giza, Cairo 12622, Egypt; abeermadel2003@yahoo.com (A.M.A.); mt.el-shemy@nrc.sci.eg (M.T.A.-S.) 3 Institute for the Study of Nanostructured Materials, National Council of Research, Via P. Gobetti, 40129 Bologna, Italy; marianna.barbalinardo@ismn.cnr.it (M.B.); denis.gentili@cnr.it (D.G.); massimiliano.cavallini@cnr.it (M.C.) 4 Institute of Crystallography, National Council of Research, Via Salaria Km 29,300, Monterotondo, 00015 Rome, Italy; roberta.montanari@cnr.it * Correspondence: daniela.caschera@cnr.it Abstract: Materials possessing long-term antibacterial behavior and high cytotoxicity are of extreme interest in several applications, from biomedical devices to food packaging. Furthermore, for the safeguard of the human health and the environment, it is also stringent keeping in mind the need to gather good functional performances with the development of ecofriendly materials and pro- cesses. In this study, we propose a green fabrication method for the synthesis of silver nanoparticles supported on oxidized nanocellulose (ONCs), acting as both template and reducing agent. The complete structural and morphological characterization shows that well-dispersed and crystalline Ag nanoparticles of about 10–20 nm were obtained in the cellulose matrix. The antibacterial properties of Ag-nanocomposites (Ag–ONCs) were evaluated through specific Agar diffusion tests against E. coli bacteria, and the results clearly demonstrate that Ag–ONCs possess high long-lasting antibacterial behavior, retained up to 85% growth bacteria inhibition, even after 30 days of incubation. Finally, cell viability assays reveal that Ag-ONCs show a significant cytotoxicity in mouse embryonic fibroblasts. Keywords: green synthesis; silver-cellulose nanocomposites; long lasting antibacterial properties; cy- totoxicity 1. Introduction Several deadly infections originated by bacteria and viruses can seriously threat human health [1]. Thus, the development of materials and devices with long lasting an- tibacterial effects and high cytotoxic behavior is of great importance [2]. Recently, cellulose and its derivatives have found several applications in the fabrication of environmentally friendly and biocompatible products due to their excellent physical and biological prop- erties, biocompatibility and biodegradability [3]. Cellulose itself usually does not show antibacterial properties, and its extreme hygroscopicity can concur to the creation of a breeding ground for bacteria growth [4], limiting strongly the application of cellulose-based materials in technological fields such as biomedicine, cosmetics, food packaging, and tissue engineering [5]. However, the opportune combination of cellulose with organic and/or inorganic materials can produce an effective biomedical agent with antibacterial activity. Materials 2021, 14, 4198. https://doi.org/10.3390/ma14154198 https://www.mdpi.com/journal/materials