The antibacterial effect of nanosilver fluoride in relation to caries activity in primary teeth: a protocol for a randomized controlled clinical trial

Nour Ammar, Magda M El-Tekeya, Sara Essa, Marwa M Essawy, Samar N El Achy, Dalia M Talaat, Nour Ammar, Magda M El-Tekeya, Sara Essa, Marwa M Essawy, Samar N El Achy, Dalia M Talaat

Abstract

Background: Minimally invasive dentistry is a highly convenient and efficient method of managing caries in pediatric patients. Silver diamine fluoride (SDF) is commonly used to arrest active caries lesions. However, the associated black stain, possibility of soft tissue injury, and unpleasant taste often limit its use. Recently, nanosilver fluoride (NSF) emerged as a promising topical fluoride agent with potent cariostatic and antibacterial potentials. This novel anticaries agent has gained attention as an alternative to overcome the drawbacks of SDF in caries arrest.

Objectives: To assess the antibacterial effect of NSF in relation to caries activity in dentin caries lesions, as well as to investigate the change in saliva bacterial levels in primary teeth in comparison to SDF after 1 and 3 months.

Materials and methods: Fifty children aged 4 to 6 years old with active dentin caries lesions (score 5 according to International Detection and Assessment System (ICDAS II) criteria) will be enrolled in the study. They will be equally and randomly allocated into 2 groups: a group receiving NSF and a control group receiving SDF treatment. Microbiological samples will be collected from the carious lesions and from unstimulated saliva at the baseline and at the 1 and 3 months' follow-up appointments. Bacterial counts will be assessed using Mitis Salivarius agar (selective culture media for S. mutans) and Rogosa agar (selective culture media for lactobacilli), and the results will be expressed in colony-forming units. Data regarding the children's oral health will be collected and their dmf index will be scored. The arrest of active carious lesions will be measured at the follow-up appointments according to ICDAS II criteria.

Results: The relation between bacterial colony counts and lesion activity for both groups will be assessed, as well as the change in salivary bacterial counts. The collected data will be statistically evaluated and tabulated. This clinical trial has been registered on ClinicalTrials.gov in January 2022 (original version) with ID: NCT05221749.

Keywords: Antibacterial; Caries; Clinical trial; Microbiology; Nanosilver fluoride; Pediatric dentistry; Primary teeth; Saliva; Silver diamine fluoride.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Study plan flowchart
Fig. 2
Fig. 2
Study timeline

References

    1. Kassebaum NJ, Smith AGC, Bernabé E, Fleming TD, Reynolds AE, Vos T, et al. Global, Regional, and national prevalence, incidence, and disability-adjusted life years for oral conditions for 195 countries, 1990-2015: a systematic analysis for the global burden of diseases, injuries, and risk factors. J Dent Res. 2017;96(4):380–387. doi: 10.1177/0022034517693566.
    1. Gao SS, Zhang S, Mei ML, Lo ECM, Chu CH. Caries remineralisation and arresting effect in children by professionally applied fluoride treatment - a systematic review. BMC Oral Health. 2016;16(1):1–9. doi: 10.1186/s12903-016-0171-6.
    1. Milgrom P, Horst JA, Ludwig S, Rothen M, Chaffee BW, Lyalina S, et al. Topical silver diamine fluoride for dental caries arrest in preschool children: A randomized controlled trial and microbiological analysis of caries associated microbes and resistance gene expression. J Dent. 2018;68:72–78. doi: 10.1016/j.jdent.2017.08.015.
    1. Gao SS, Chen KJ, Duangthip D, Wong MCM, Lo ECM, Chu CH. Arresting early childhood caries using silver and fluoride products – a randomised trial. J Dent. 2020;103(103522).
    1. Rosenblatt A, Stamford TCM, Niederman R. Silver diamine fluoride: A caries “silver-fluoride bullet.”. J Dent Res. 2009;88(2):116–125. doi: 10.1177/0022034508329406.
    1. Jabin Z, Vishnupriya V, Agarwal N, Nasim I, Jain M, Sharma A. Effect of 38% silver diamine fluoride on control of dental caries in primary dentition: a systematic review. J Fam Med Prim Care. 2020;9(3):1302. doi: 10.4103/jfmpc.jfmpc_1017_19.
    1. Horst JA, Ellenikiotis H, Committee USCA, Milgrom PM. UCSF protocol for caries arrest using silver diamine fluoride: rationale, indications, and consent. J Calif Dent Assoc. 2016;44(1):16.
    1. El-Allaky HS, Wahba NA, Talaat DM, Zakaria AS. Antimicrobial effect of propolis administered through two different vehicles in high caries risk children: a randomized clinical trial. J Clin Pediatr Dent. 2020;44(5):289–295. doi: 10.17796/1053-4625-44.5.1.
    1. Frencken JE. Dental caries and caries epidemiology. In: Eden E, editor. Evidence-based caries prevention. Cham: Springer; 2016. pp. 1–11.
    1. Targino AGR, Flores MAP, Dos Santos VE, De Godoy Bené Bezerra F, De Luna Freire H, Galembeck A, et al. An innovative approach to treating dental decay in children. A new anti-caries agent. J Mater Sci Mater Med. 2014;25(8):2041–2047. doi: 10.1007/s10856-014-5221-5.
    1. Durán N, Silveira CP, Durán M, Martinez DST. Silver nanoparticle protein corona and toxicity: a mini-review. J Nanobiotechnol. 2015;13(1):1–17. doi: 10.1186/s12951-015-0114-4.
    1. Sayed M, Tsuda Y, Matin K, Abdou A, Martin K, Burrow MF, et al. Effects of mechanical abrasion challenge on sound and demineralized dentin surfaces treated with SDF. Sci Rep. 2020;10(1) [cited 2021 Sep 27]. Available from: 10.1038/s41598-020-77035-9.
    1. Teixeira JA, Costa E, Silva AV, Dos Santos VE, De Melo PC, Arnaud M, et al. Effects of a new nano-silver fluoride-containing dentifrice on demineralization of enamel and Streptococcus mutans adhesion and acidogenicity. Int J Dent. 2018;2018 [cited 2021 Sep 27]. Available from: .
    1. Vieira Costa E Silva A, Teixeira JA, Mota CCBO, Clayton Cabral Correia Lins E, Correia De Melo P, De Souza Lima MG, et al. In vitro morphological, optical and microbiological evaluation of nanosilver fluoride in the remineralization of deciduous teeth enamel. Nanotechnol Rev. 2018;7(6):509–520. doi: 10.1515/ntrev-2018-0083.
    1. Yin IX, Zhang J, Zhao IS, Mei ML, Li Q, Chu CH. The antibacterial mechanism of silver nanoparticles and its application in dentistry. Int J Nanomedicine. 2020;15:2555–2562. doi: 10.2147/IJN.S246764.
    1. Haghgoo R, Saderi H, Eskandari M, Haghshenas H, Rezvani M. Evaluation of the antimicrobial effect of conventional and nanosilver-containing varnishes on oral streptococci. J Dent (Shiraz, Iran) 2014;15(2):57–62.
    1. Tirupathi S, Nirmala SVSG, Rajasekhar S, Nuvvula S. Comparative cariostatic efficacy of a novel nano-silver fluoride varnish with 38% silver diamine fluoride varnish a double-blind randomized clinical trial. J Clin Exp Dent. 2019;11(2):e105–e112. doi: 10.4317/jced.54995.
    1. Puppala N, Nagireddy VR, Reddy D, Kondamadugu S, Mareddy A, Chris A. Nanosilver fluoride—a paradigm shift for arrest in dental caries in primary teeth of schoolchildren: a randomized controlled clinical trial. Int J Clin Pediatr Dent. 2019;12(6):484–490. doi: 10.5005/jp-journals-10005-1703.
    1. Schulz KF, Altman DG, Moher D. CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. BMC Med. 2010;8(1):1–9. doi: 10.1186/1741-7015-8-18.
    1. Rosner B. Fundamentals of biostatistics. 7. Boston: Brooks/Cole. Nelson Education; 2015. Hypothesis Testing: Two-Sample Inference; pp. 269–301.
    1. Faul F, Erdfelder E. G*Power for Windows (version 3.1.9.7). G*Power. Düsseldorf: Universität Düsseldorf. [cited 2021 Oct 2]. Available from:
    1. Ismail AI, Sohn W, Tellez M, Amaya A, Sen A, Hasson H, et al. The International Caries Detection and Assessment System (ICDAS): an integrated system for measuring dental caries: Methods. Community Dent Oral Epidemiol. 2007;35(3):170–178. doi: 10.1111/j.1600-0528.2007.00347.x.
    1. Mitwalli H, Mourao MDA, Dennison J, Yaman P, Paster BJ, Fontana M. Effect of silver diamine fluoride treatment on microbial profiles of plaque biofilms from root/cervical caries lesions. Caries Res. 2019;53(5):555–566. doi: 10.1159/000499578.
    1. Agency for Toxic Substances and Disease Registry . Toxicological profiles. 2005.
    1. Haahr M. True Random Number Service. 2012.
    1. Schulz KF, Grimes DA. Allocation concealment in randomised trials: defending against deciphering. Lancet. 2002;359:614–618. doi: 10.1016/S0140-6736(02)07750-4.
    1. International Caries Classification and Management System (ICCMS). ICDAS Foundation. ICDAS elearning courses. Available from:
    1. American Academy of Pediatric dentistry Chairside guide: Silver diamine fluoride in the management of dental caries lesions. Pediatr Dent. 2017;39(6):478–479.
    1. Gakiya-Teruya M, Palomino-Marcelo L, Rodriguez-Reyes JCF. Synthesis of highly concentrated suspensions of silver nanoparticles by two versions of the chemical reduction method. Methods Protoc. 2019;2(1):1–5.
    1. Raouf M, Essa S, El Achy S, Essawy M, Rafik S, Baddour M. Evaluation of combined ciprofloxacin and azithromycin free and nano formulations to control biofilm producing Pseudomonas aeruginosa isolated from burn wounds. Indian J Med Microbiol. 2021;39(1):81–87. doi: 10.1016/j.ijmmb.2021.01.004.
    1. Essawy MM, El-Sheikh SM, Raslan HS, Ramadan HS, Kang B, Talaat IM, et al. Function of gold nanoparticles in oral cancer beyond drug delivery: implications in cell apoptosis. Oral Dis. 2021;27(2):251–265. doi: 10.1111/odi.13551.
    1. Jiménez-Ramírez AJ, Martínez-Martínez RE, Ayala-Herrera JL, Zaragoza-Contreras EA, Domínguez-Pérez RA, Reyes-López SY, et al. Antimicrobial Activity of Silver Nanoparticles against Clinical Biofilms from Patients with and without Dental Caries. J Nanomater. 2021;2021:13. Article ID 5587455. 10.1155/2021/5587455.
    1. Weinstein MP. M100 performance standards for antimicrobial susceptibility testing. 31 2021.
    1. Petersen PE, Baez RJ, Organization WH . Oral health surveys; basic methods. 5. Geneva: World Health Organization; 1977. pp. 115–118.
    1. Çağlar E, Kuşcu OO. The role of diet in caries prevention. Evid-Based Caries Prev. 2016;51:87–106. doi: 10.1007/978-3-319-40034-1_6.
    1. Kamate WI, Vibhute NA, Baad RK. Estimation of DMFT, salivary streptococcus mutans count, flow rate, Ph, and salivary total calcium content in pregnant and non-pregnant women: A prospective study. J Clin Diagn Res. 2017;11(4):XC01–XC05.
    1. Rishmawi N, Ghneim R, Kattan R, Ghneim R, Zoughbi M, Abu-Diab A, et al. Survival of fastidious and nonfastidious aerobic bacteria in three bacterial transport swab systems. J Clin Microbiol. 2007;45(4):1278–1283. doi: 10.1128/JCM.02110-06.
    1. Elevate Oral Care. Safety data sheet Safety data sheet, advantage arrest 38 % silver diamine fluoride. 2005 1173.. p. 1–8. [cited 2021 Sep 28]. Available from:
    1. Karched M, Ali D, Ngo H. In vivo antimicrobial activity of silver diammine fluoride on carious lesions in dentin. J Oral Sci. 2019;61(1):19–24. doi: 10.2334/josnusd.17-0366.
    1. Ravindran S, Chaudhary M, Gawande M. Enumeration of salivary Streptococci and Lactobacilli in children with differing caries experiences in a rural Indian population. ISRN Plast Surg. 2013;2013:1–6. doi: 10.5402/2013/476783.
    1. Rubin DB. Multiple imputation for nonresponse in surveys. Wiley. 2004; [cited 2022 Jun 5]. Available from: .
    1. U.S Food & Drug Administration . Diammine silver fluoride dental hypersensitivity varnish. 2014.
    1. Sabbagh H, Othman M, Khogeer L, Al-Harbi H, Al Harthi A, Abdulgader Yaseen Abdulgader A. Parental acceptance of silver diamine fluoride application on primary dentition: a systematic review and meta-analysis. BMC Oral Health. 2020;20(1):1–12. doi: 10.1186/s12903-020-01195-3.
    1. Espíndola-Castro LF, Rosenblatt A, Galembeck A, de Melo Monteiro GQ. Dentin staining caused by nano-silver fluoride: a comparative study. Oper Dent. 2020;45(4):435–441. doi: 10.2341/19-109-L.
    1. Sibbald RG, Contreras-Ruiz J, Coutts P, Fierheller M, Rothman A, Woo K. Bacteriology, inflammation, and healing: a study of nanocrystalline silver dressings in chronic venous leg ulcers. Adv Skin Wound Care. 2007;20(10):549–558. doi: 10.1097/01.ASW.0000294757.05049.85.
    1. Skirtach AG, Muñoz Javier A, Kreft O, Köhler K, Piera Alberola A, Möhwald H, et al. Laser-induced release of encapsulated materials inside living cells. Angew Chem Int Ed Engl. 2006;45(28):4612–4617. doi: 10.1002/anie.200504599.
    1. Galiano K, Pleifer C, Engelhardt K, Brössner G, Lackner P, Huck C, et al. Silver segregation and bacterial growth of intraventricular catheters impregnated with silver nanoparticles in cerebrospinal fluid drainages. Neurol Res. 2008;30(3):285–287. doi: 10.1179/016164107X229902.
    1. Moore K. A new silver dressing for wounds with delayed healing Product REVIEW KEY WORDS Atrauman Ag Chronic wound Critical colonisation Wound infection Silver dressing. Wounds UK. 2006;2(2):70–76.
    1. Ammar N, Aly NM, Folayan MO, Khader Y, Mohebbi SZ, Attia S, et al. Perceived preparedness of dental academic institutions to cope with the covid-19 pandemic: a multi-country survey. Int J Environ Res Public Health. 2021;18(4):1–15. doi: 10.3390/ijerph18041445.
    1. Burns J, Hollands K. Nano Silver Fluoride for preventing caries. Evid Based Dent. 2015;16(1):8–9. doi: 10.1038/sj.ebd.6401073.
    1. Ferdous Z, Nemmar A. Health impact of silver nanoparticles: a review of the biodistribution and toxicity following various routes of exposure. Int J Mol Sci. 2020;21(7) [cited 2022 Jan 24]. Available from: /pmc/articles/PMC7177798/.
    1. Dos Santos VE, Filho AV, Ribeiro Targino AG, Pelagio Flores MA, Galembeck A, Caldas AF, et al. A new “silver-bullet” to treat caries in children – nano silver fluoride: a randomised clinical trial. J Dent. 2014;42(8):945–951. doi: 10.1016/j.jdent.2014.05.017.
    1. National Library of Medicine, National Center for Biotechnology Information. Sodium borohydride | - PubChem. [cited 2021 Dec 17]. Available from:
    1. New Jersey Department of Health and Senior Services . Hazardous Substances Fact Sheet - Sodium Borohydride. 2007.
    1. U.S. Food & Drug Administration . Sodium citrate. CFR - Code of Federal Regulations. 1987. pp. 5–6.
    1. National Library of Medicine, National Center for Biotechnology Information. Trisodium citrate dihydrate | C6H9Na3O9 - PubChem. PubChem - NIH. [cited 2021 Dec 17]. Available from:
    1. U.S Food and Drug Administration . Drugs@FDA: FDA-approved drugs. Drug Databases. 2021.
    1. National Cancer Institute at the National Institutes of Health . NCI Dictionary of Cancer Terms - PEG. National Cancer Institute; 2021. pp. 3–5.
    1. Dikmen B. Icdas Ii Criteria (International Caries Detection and Assessment System) J Istanbul Univ Fac Dent. 2015;49(3):63. doi: 10.17096/jiufd.38691.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다