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Comparison of the clinical effects of subgingival application of metronidazole 25% gel and scaling in the treatment of adult periodontitis. Quintessence Int. 1998, 29:41-8.","journal-title":"Quintessence Int"},{"key":"ref112","article-title":"Clinical evaluation of subgingival application of metronidazole 25%, and adjunctive therapy","volume":"2","author":"Al-Mubarak SA","year":"2000","unstructured":"Al-Mubarak SA, Karring T, Ho A. Clinical evaluation of subgingival application of metronidazole 25%, and adjunctive therapy. J Int Acad Periodontol. 2000, 2:64-70.","journal-title":"J Int Acad Periodontol"},{"key":"ref113","doi-asserted-by":"publisher","DOI":"10.1902\/jop.1998.69.10.1148","article-title":"Local metronidazole application in maintenance patients. Clinical and microbiological evaluation","volume":"69","author":"Rudhart A","year":"1998","unstructured":"Rudhart A, Purucker P, Kage A, Hopfenm\u00fcller W, Bernimoulin JP. Local metronidazole application in maintenance patients. Clinical and microbiological evaluation. J Periodontol. 1998, 69:1148-54. 10.1902\/jop.1998.69.10.1148","journal-title":"J Periodontol"},{"key":"ref114","article-title":"Repeated oral hygiene instructions alone, or in combination with metronidazole dental gel with or without subgingival scaling in adult periodontitis patients: a one-year clinical study","volume":"8","author":"Zee KY","year":"2006","unstructured":"Zee KY, Lee DH, Corbet EF. Repeated oral hygiene instructions alone, or in combination with metronidazole dental gel with or without subgingival scaling in adult periodontitis patients: a one-year clinical study. J Int Acad Periodontol. 2006, 8:125-35.","journal-title":"J Int Acad Periodontol"},{"key":"ref115","doi-asserted-by":"publisher","DOI":"10.2174\/2210303110999200910104334","article-title":"Metronidazole loaded polycaprolactone-carbopol blends based biodegradable intrapocket dental film for local treatment of periodontitis","volume":"11","author":"Dhedage N","year":"2021","unstructured":"Dhedage N, Khan G, Ajmal G, Kumar M, Jha A, Mishra B. Metronidazole loaded polycaprolactone-carbopol blends based biodegradable intrapocket dental film for local treatment of periodontitis. Drug Deliv Lett. 2021, 11:34-43. 10.2174\/2210303110999200910104334","journal-title":"Drug Deliv Lett"},{"key":"ref116","doi-asserted-by":"publisher","DOI":"10.3390\/app9214545","article-title":"Metronidazole-loaded porous matrices for local periodontitis treatment: in vitro evaluation and in vivo pilot study","volume":"9","author":"Kida D","year":"2019","unstructured":"Kida D, Karolewicz B, Junka A, Sender-Janeczek A, Du\u015b I, Marciniak D, Szulc M. Metronidazole-loaded porous matrices for local periodontitis treatment: in vitro evaluation and in vivo pilot study. Appl Sci. 2019, 9:4545. 10.3390\/app9214545","journal-title":"Appl Sci"},{"key":"ref117","doi-asserted-by":"publisher","DOI":"10.1111\/jre.12278","article-title":"Full mouth periodontal debridement with or without adjunctive metronidazole gel in smoking patients with chronic periodontitis: a pilot study","volume":"51","author":"Bergamaschi CC","year":"2016","unstructured":"Bergamaschi CC, Santamaria MP, Berto LA, et al.. Full mouth periodontal debridement with or without adjunctive metronidazole gel in smoking patients with chronic periodontitis: a pilot study. J Periodontal Res. 2016, 51:50-9. 10.1111\/jre.12278","journal-title":"J Periodontal Res"},{"key":"ref118","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9080975","article-title":"Metronidazole- and amoxicillin-loaded PLGA and PCL nanofibers as potential drug delivery systems for the treatment of periodontitis: in vitro and in vivo evaluations","volume":"9","author":"Mirzaeei S","year":"2021","unstructured":"Mirzaeei S, Mansurian M, Asare-Addo K, Nokhodchi A. Metronidazole- and amoxicillin-loaded PLGA and PCL nanofibers as potential drug delivery systems for the treatment of periodontitis: in vitro and in vivo evaluations. Biomedicines. 2021, 9:975. 10.3390\/biomedicines9080975","journal-title":"Biomedicines"},{"key":"ref119","article-title":"Clinical effects of metronidazole-ofloxacin gel as an adjunct to conventional therapy for periodontitis (Article in Chinese)","volume":"19","author":"Yang H","year":"2001","unstructured":"Yang H, Wang X, Xu Y, Zhang J. Clinical effects of metronidazole-ofloxacin gel as an adjunct to conventional therapy for periodontitis (Article in Chinese). Hua Xi Kou Qiang Yi Xue Za Zhi. 2001, 19:35-7.","journal-title":"Hua Xi Kou Qiang Yi Xue Za Zhi"},{"key":"ref120","article-title":"Effectiveness of local drug delivery system using 1% metronidazole gel and mouthwash in treating periodontal diseases","volume":"33","author":"Hasan F","year":"2020","unstructured":"Hasan F, Ikram R, Abbas A, Asadullah K. Effectiveness of local drug delivery system using 1% metronidazole gel and mouthwash in treating periodontal diseases. Pak J Pharm Sci. 2020, 33:2053-8.","journal-title":"Pak J Pharm Sci"},{"key":"ref121","doi-asserted-by":"publisher","DOI":"10.1080\/10717544.2017.1359703","article-title":"An injectable in situ gel with cubic and hexagonal nanostructures for local treatment of chronic periodontitis","volume":"24","author":"Mei L","year":"2017","unstructured":"Mei L, Huang X, Xie Y, et al.. An injectable in situ gel with cubic and hexagonal nanostructures for local treatment of chronic periodontitis. Drug Deliv. 2017, 24:1148-58. 10.1080\/10717544.2017.1359703","journal-title":"Drug Deliv"},{"key":"ref122","doi-asserted-by":"crossref","DOI":"10.2298\/VSP0508565T","article-title":"Effects of topical application of metronidazole-containing mucoadhesive Lipogel in periodontal pockets. Vojnosanitetski pregled military-medical and pharmaceutical review","volume":"62","author":"Toski\u0107-Radojici\u0107 M","year":"2005","unstructured":"Toski\u0107-Radojici\u0107 M, Nonkovi\u0107 Z, Loncar I, Varjaci\u0107 M. Effects of topical application of metronidazole-containing mucoadhesive Lipogel in periodontal pockets. Vojnosanitetski pregled military-medical and pharmaceutical review. Vojnosanit Pregl. 2005, 62:565\u22128.","journal-title":"Vojnosanit Pregl"},{"key":"ref123","doi-asserted-by":"publisher","DOI":"10.4103\/0972-124X.60224","article-title":"Evaluation of two local drug delivery systems as adjuncts to mechanotherapy as compared to mechanotherapy alone in management of chronic periodontitis: a clinical, microbiological, and molecular study","volume":"13","author":"Singh S","year":"2009","unstructured":"Singh S, Roy S, Chumber SK. Evaluation of two local drug delivery systems as adjuncts to mechanotherapy as compared to mechanotherapy alone in management of chronic periodontitis: a clinical, microbiological, and molecular study. J Indian Soc Periodontol. 2009, 13:126-32. 10.4103\/0972-124X.60224","journal-title":"J Indian Soc Periodontol"},{"key":"ref124","doi-asserted-by":"publisher","DOI":"10.4103\/0976-237X.111615","article-title":"Comparative evaluation of locally delivered minocycline and metronidazole in the treatment of periodontitis","volume":"4","author":"Pandit N","year":"2013","unstructured":"Pandit N, Dahiya R, Gupta R, Bali D, Kathuria A. Comparative evaluation of locally delivered minocycline and metronidazole in the treatment of periodontitis. Contemp Clin Dent. 2013, 4:48-53. 10.4103\/0976-237X.111615","journal-title":"Contemp Clin Dent"},{"key":"ref125","doi-asserted-by":"publisher","DOI":"10.1007\/s42452-020-2362-7","article-title":"Designing a novel chitosan-based periofilm containing metronidazole-ciprofloxacin","volume":"5","author":"Boroujeni AA","year":"2020","unstructured":"Boroujeni AA, Ardakani MT, Houshmand B, Moscowchi A. Designing a novel chitosan-based periofilm containing metronidazole-ciprofloxacin. SN Appl Sci. 2020, 5:558. 10.1007\/s42452-020-2362-7","journal-title":"SN Appl Sci"},{"key":"ref126","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms8050661","article-title":"The microbiome of peri-implantitis: a systematic review and meta-analysis","volume":"8","author":"Sahrmann P","year":"2020","unstructured":"Sahrmann P, Gilli F, Wiedemeier DB, Attin T, Schmidlin PR, Karygianni L. The microbiome of peri-implantitis: a systematic review and meta-analysis. Microorganisms. 2020, 8:661. 10.3390\/microorganisms8050661","journal-title":"Microorganisms"},{"key":"ref127","doi-asserted-by":"publisher","DOI":"10.1186\/1746-160X-10-34","article-title":"Definition, etiology, prevention and treatment of peri-implantitis--a review","volume":"10","author":"Smeets R","year":"2014","unstructured":"Smeets R, Henningsen A, Jung O, Heiland M, Hamm\u00e4cher C, Stein JM. Definition, etiology, prevention and treatment of peri-implantitis--a review. Head Face Med. 2014, 10:34. 10.1186\/1746-160X-10-34","journal-title":"Head Face Med"},{"key":"ref128","article-title":"Peri-implant mucositis and peri-implantitis: clinical and histopathological characteristics and treatment","volume":"67","author":"Khammissa RA","year":"2012","unstructured":"Khammissa RA, Feller L, Meyerov R, Lemmer J. Peri-implant mucositis and peri-implantitis: clinical and histopathological characteristics and treatment. SADJ. 2012, 67:122, 124-6.","journal-title":"SADJ"},{"key":"ref129","doi-asserted-by":"publisher","DOI":"10.1308\/205016813806144209","article-title":"An insight into peri-implantitis: a systematic literature review","volume":"2","author":"Wilson V","year":"2013","unstructured":"Wilson V. An insight into peri-implantitis: a systematic literature review. Prim Dent J. 2013, 2:69-73. 10.1308\/205016813806144209","journal-title":"Prim Dent J"},{"key":"ref130","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1149055","article-title":"Efficacy of adjuvant metronidazole therapy on peri-implantitis: a systematic review and meta-analysis of randomized clinical studies","volume":"13","author":"L\u00f3pez-Valverde N","year":"2023","unstructured":"L\u00f3pez-Valverde N, L\u00f3pez-Valverde A, Blanco-Rueda JA. Efficacy of adjuvant metronidazole therapy on peri-implantitis: a systematic review and meta-analysis of randomized clinical studies. Front Cell Infect Microbiol. 2023, 13:1149055. 10.3389\/fcimb.2023.1149055","journal-title":"Front Cell Infect Microbiol"},{"key":"ref131","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.2008.01276.x","article-title":"Non-surgical treatment of peri-implant mucositis and peri-implantitis: a literature review","volume":"35","author":"Renvert S","year":"2008","unstructured":"Renvert S, Roos-Jans\u00e5ker AM, Claffey N. Non-surgical treatment of peri-implant mucositis and peri-implantitis: a literature review. J Clin Periodontol. 2008, 35:305-15. 10.1111\/j.1600-051X.2008.01276.x","journal-title":"J Clin Periodontol"},{"key":"ref132","doi-asserted-by":"publisher","DOI":"10.11607\/jomi.7343","article-title":"Adjunctive systemic metronidazole to nonsurgical therapy of peri-implantitis with intrabony defects: a retrospective case series study","volume":"34","author":"Li\u00f1ares A","year":"2019","unstructured":"Li\u00f1ares A, Pico A, Blanco C, Blanco J. Adjunctive systemic metronidazole to nonsurgical therapy of peri-implantitis with intrabony defects: a retrospective case series study. Int J Oral Maxillofac Implants. 2019, 34:1237-45. 10.11607\/jomi.7343","journal-title":"Int J Oral Maxillofac Implants"},{"key":"ref133","doi-asserted-by":"publisher","DOI":"10.1111\/idj.12034","article-title":"Clinical efficacy of antibiotics in the treatment of peri-implantitis","volume":"63","author":"Javed F","year":"2013","unstructured":"Javed F, Alghamdi AS, Ahmed A, Mikami T, Ahmed HB, Tenenbaum HC. Clinical efficacy of antibiotics in the treatment of peri-implantitis. 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