  Citation: Dascalu, L.M.; Moldovan, M.; Sarosi, C.; Sava, S.; Dreanca, A.; Repciuc, C.; Purdoiu, R.; Nagy, A.; Badea, M.E.; Paun, A.G.; et al. Photodynamic Therapy with Natural Photosensitizers in the Management of Periodontal Disease Induced in Rats. Gels 2022, 8, 134. https:// doi.org/10.3390/gels8020134 Academic Editors: Arish Dasan, Ashokraja Chandrasekar and Nupur Kohli Received: 19 January 2022 Accepted: 17 February 2022 Published: 20 February 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 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/). gels Article Photodynamic Therapy with Natural Photosensitizers in the Management of Periodontal Disease Induced in Rats Laura Monica Dascalu (Rusu) 1 , Marioara Moldovan 2 , Codruta Sarosi 2, * , Sorina Sava 1, *, Alexandra Dreanca 3,† , Calin Repciuc 3 , Robert Purdoiu 3 , Andras Nagy 3 , Mîndra Eugenia Badea 4 , Ariadna Georgiana Paun 5 , Iulia Clara Badea 4,† and Radu Chifor 4 1 Department of Prosthodontics and Dental Materials, Iuliu Hatieganu University of Medicine and Pharmacy, 31 Avram Iancu Str., 400083 Cluj-Napoca, Romania; dascalu.monica@umfcluj.ro 2 Raluca Ripan Institute of Chemistry, Babes-Bolyai University, 30 Fantanele Str., 400294 Cluj-Napoca, Romania; marioara.moldovan@ubbcluj.ro 3 Pathophysiology/Toxicology Department, Faculty of Veterinary Medicine, University of Agricultural Science and Veterinary Medicine, 3-5 Calea Manastur, 400372 Cluj-Napoca, Romania; alexandradreanca@gmail.com (A.D.); calin_c_repciuc@yahoo.com (C.R.); robert.purdoiu@usamvcluj.ro (R.P.); nagyandras26@gmail.com (A.N.) 4 Department of Preventive Dental Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 31 Avram Iancu Str., 400083 Cluj-Napoca, Romania; mebadea@umfcluj.ro (M.E.B.); iulia.badea@umfcluj.ro (I.C.B.); chifor.radu@umfcluj.ro (R.C.) 5 Department Community Medicine, Iuliu Hat , ieganu University of Medicine and Pharmacy, 31 Avram Iancu Str., 400083 Cluj-Napoca, Romania; badea.ariadna@umfcluj.ro * Correspondence: codruta.sarosi@gmail.com (C.S.); savasorina@yahoo.com (S.S.); Tel.: +40-742010325 (C.S.) † These authors contributed equally to this work. Abstract: This study aims to investigate the effect of new natural photosensitizers (PS) (based on oregano essential oil, curcuma extract, and arnica oil) through in vitro cytotoxicity and biological tests in rat-induced periodontal disease, treated with photodynamic therapy (aPDT). The cytotoxicity of PS was performed on human dental pulp mesenchymal stem cells (dMSCs) and human keratinocyte (HaCaT) cell lines. Periodontal disease was induced by ligation of the first mandibular molar of 25 rats, which were divided into 5 groups: control group, periodontitis group, Curcuma and aPDT- treated group, oregano and aPDT-treated group, and aPDT group. The animals were euthanized after 4 weeks of study. Computed tomography imaging has been used to evaluate alveolar bone loss. Hematological and histological evaluation showed a greater magnitude of the inflammatory response and severe destruction of the periodontal ligaments in the untreated group.. For the group with the induced periodontitis and treated with natural photosensitizers, the aPDT improved the results; this therapy could be an important adjuvant treatment. The obtained results of these preliminary studies encourage us to continue the research of periodontitis treated with natural photosensitizers activated by photodynamic therapy. Keywords: gels; photosensitizers; photodynamic therapy; cytotoxicity; computed tomography 1. Introduction There are a number of oral diseases that pose a major threat to public health worldwide, among which periodontal diseases and dental caries are the most invasive and difficult to treat. The need to develop an alternative prevention treatment with antibacterial agents is due to the side effects of conventionally used treatments (antibacterial, anti-inflammatory, or antibiotic drugs) and the increasing bacterial resistance to them. Thus, natural products and photodynamic therapy has become a topical and important research subject. Periodontitis is a very common chronic inflammatory disease nowadays. It is caused by infection with the presence of various types of oral bacteria, the so-called “red com- plex”, which includes, among others, Porphyromonas gingivalis, Tannerella forsythia, Gels 2022, 8, 134. https://doi.org/10.3390/gels8020134 https://www.mdpi.com/journal/gels