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nanomaterials Article Silver Nanoparticles-Composing Alginate/Gelatine Hydrogel Improves Wound Healing In Vivo Flavia Resende Diniz 1,2, Romerito Cesar A. P. Maia 1, Lucas Rannier Andrade 1, Luciana Nalone Andrade 1, Marco Vinicius Chaud 3 , Classius Ferreira da Silva 4, Cristiane Bani Corrêa 5, Ricardo Luiz C. de Albuquerque Junior 1, Luiz Pereira da Costa 1, Su Ryon Shin 6, Shabir Hassan 6, Elena Sanchez-Lopez 7,8 , Eliana Barbosa Souto 2,9,* and Patricia Severino 1,10,* 1 2 3 4 5 6 7 8 9 10 * Tiradentes University (UNIT) and Institute of Technology and Research (ITP), Av. Murilo Dantas 300, Aracaju 49032-490, Brazil; flavinhadiniz_se@hotmail.com (F.R.D.); romeritocesar@hotmail.com (R.C.A.P.M.); rannier.andrade@outlook.com (L.R.A.); luciana.nalone@hotmail.com (L.N.A.); ricardo_albuquerque@unit.br (R.L.C.d.A.J.); lupeco7@hotmail.com (L.P.d.C.) Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal Department of Technological and Environmental Processes, Sorocaba University (UNISO), Rod. Raposo Tavares, Km 92.5, Sorocaba 18023-000, Brazil; marco.chaud@prof.uniso.br Department of Exact Sciences and Earth, Federal University of São Paulo (UNIFESP), Rua Prof. Artur Riedel, 275, Diadema CEP 09972-270, Brazil; classiusferreira@yahoo.com.br Department of Morphology, Federal University of Sergipe (UFS), Avenida Marechal Rondon, São Cristovão 49100-000, Brazil; crisbani@gmail.com Center for Biomedical Engineering, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USA; sshin4@bwh.harvard.edu (S.R.S.); SHASSAN@bwh.harvard.edu (S.H.) Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences and Institute of Nanoscience and nanotechnology (IN2UB), University of Barcelona, Av. Joan XXIII 27-31, 08028 Barcelona, Spain; esanchezlopez@ub.edu CIBERNED Centros de Biomedicina en Red de Enfermedades Neurodegenerativas, Facultat de Farmàcia, Universitat de Barcelona, 08028 Barcelona, Spain CEB - Centre of Biological Engineering, University of Minho, Campus de Gualtar 4710-057 Braga, Portugal Tiradentes Institute, 150 Mt Vernon St, Dorchester, MA 02125, USA Correspondence: ebsouto@ff.uc.pt (E.B.S.); patricia_severino@itp.org.br (P.S.); Tel.: +351-239-488-400 (E.B.S.); +55 (79) 3218-2190 (P.S.) Received: 8 January 2020; Accepted: 19 February 2020; Published: 23 February 2020 Abstract: Polymer hydrogels have been suggested as dressing materials for the treatment of cutaneous wounds and tissue revitalization. In this work, we report the development of a hydrogel composed of natural polymers (sodium alginate and gelatin) and silver nanoparticles (AgNPs) with recognized antimicrobial activity for healing cutaneous lesions. For the development of the hydrogel, different ratios of sodium alginate and gelatin have been tested, while different concentrations of AgNO3 precursor (1.0, 2.0, and 4.0 mM) were assayed for the production of AgNPs. The obtained AgNPs exhibited a characteristic peak between 430–450 nm in the ultraviolet-visible (UV–Vis) spectrum suggesting a spheroidal form, which was confirmed by Transmission Electron Microscopy (TEM). Fourier Transform Infra-red (FT–IR) analysis suggested the formation of strong intermolecular interactions as hydrogen bonds and electrostatic attractions between polymers, showing bands at 2920, 2852, 1500, and 1640 cm−1. Significant bactericidal activity was observed for the hydrogel, with a Minimum Inhibitory Concentration (MIC) of 0.50 μg/mL against Pseudomonas aeruginosa and 53.0 μg/mL against Staphylococcus aureus. AgNPs were shown to be non-cytotoxic against fibroblast cells. The in vivo studies in female Wister rats confirmed the capacity of the AgNP-loaded hydrogels to reduce the wound size compared to uncoated injuries promoting histological changes in the healing Nanomaterials 2020, 10, 390; doi:10.3390/nano10020390 www.mdpi.com/journal/nanomaterialsPDF Image | Wound Healing Silver Nanoparticles-Composing Hydrogel
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