Repeated Home-Applied Dual-Light Antibacterial Photodynamic Therapy Can Reduce Plaque Burden, Inflammation, and aMMP-8 in Peri-Implant Disease-A Pilot Study

Hanna Lähteenmäki, Tommi Pätilä, Ismo T Räisänen, Esko Kankuri, Taina Tervahartiala, Timo Sorsa, Hanna Lähteenmäki, Tommi Pätilä, Ismo T Räisänen, Esko Kankuri, Taina Tervahartiala, Timo Sorsa

Abstract

Until now, in clinical dentistry, antibacterial photodynamic therapy (aPDT) has been restricted to in-office treatments, which hampers repeated applications. This pilot study tested the benefit of a commercially available Lumoral® device designed for regular periodontal dual-light aPDT treatment at home. Seven patients with peri-implant disease applied dual-light aPDT daily in addition to their normal dental hygiene for four weeks. A single Lumoral® treatment includes an indocyanine green mouth rinse followed by 40 J/cm2 radiant exposure to a combination of 810 nm and 405 nm light. A point-of-care analysis of active-matrix metalloproteinase (aMMP-8), visible plaque index (VPI), bleeding on probing (BOP), and peri-implant pocket depth (PPD) measurements was performed on day 0, day 15, and day 30. Reductions in aMMP-8 (p = 0.047), VPI (p = 0.03), and BOP (p = 0.03) were observed, and PPD was measured as being 1 mm lower in the implant (p = ns). These results suggest a benefit of regular application of dual-light aPDT in peri-implantitis. Frequently repeated application can be a promising approach to diminishing the microbial burden and to lowering the tissue destructive proteolytic and inflammatory load around dental implants. Further studies in larger populations are warranted to show the long-term benefits.

Keywords: aMMP-8; antibacterial photodynamic therapy; oral hygiene; peri-implant disease.

Conflict of interest statement

Timo Sorsa is the inventor of the following patents: 1274,416-patent U.S. 5,652,223, 5,736,341, 5,864,632, 6,143,476, and US 2017/0023571A1 (issued June 6, 2019); WO 2018/060553 A1 (issued May 31, 201); 10,488,415 B2, Japanese Patent 2016-554676; and South Korean patent 10-2016-7025378. Tommi Pätilä is a member of the board of Koite Health company. The company has filed patents P21233F100 and P22769F100 and owns trademarks related to antibacterial dual-light. Koite Health develops, sells, and markets dual-light antibacterial products for the prevention and treatment of dental and periodontal infections.

Figures

Figure 1
Figure 1
The dual-light aPDT device was used in the study. (A) The packaging provided for the study subjects included the effervescent ICG tablets (*) to be dissolved in 30 mL of water, for which a measuring cup (**) was provided. A power source (***) was provided for the mouthguard-type light applicator (B). The mouthpiece (*) is composed of 48 LED components (**) able to provide 405 nm and 810 nm light simultaneously. Symmetrically assembled LEDs provided light for both the maxillary and mandibular dental arches. The button on the control unit provided a treatment time of 10 min (***). Dissolved mouth rinse can be seen in the glass.
Figure 2
Figure 2
The power calculation.
Figure 3
Figure 3
The dots represent the measured individual values, the bars represent the mean, and the error bars are the standard error of the mean. (A) There was a reduction in aMMP-8 measured from PISF between the pretreatment and after four weeks of treatment. The red line represents the normal value in PISF measurements in implant patients. (B) After two weeks of single-use of the dual-light aPDT device, a suggestive reduction in VPI was measured. After the subsequent use of twice a day, VPI was significantly lower. (C) Bleeding on probing was positive in all study subjects at the beginning of the study. However, it was measured negative in three patients at four weeks. (D) One implant pocket showed a reduction in PD during the four-week study period.
Figure 4
Figure 4
This 89-year-old patient (A) showed buccal bone loss, assessed using an intraoral X-ray (B), and a gingival fistula at the study implant D13 (C). The visual plaque index measured 1/3 at the beginning of the study, with a probing depth of 4 mm. The aMMP-8 value in the peri-implant sulcular fluid was 78.18 ng/mL at the beginning of the study (D). After two weeks of Lumoral® dual-light aPDT treatment repeated once a day, the aMMP-value was 51.70 (D), after which the Lumoral® treatment was repeated twice a day for the next two weeks. At four weeks, the aMMP-8 was 23.76 ng/mL, and the visual plaque index measured 0/3. In this patient, bleeding on probing was measured positive though the whole study period, and no change was observed in the probing depth.

References

    1. Van Velzen F.J., Ofec R., Schulten E.A., Bruggenkate C.M.T. 10-year survival rate and the incidence of peri-implant disease of 374 titanium dental implants with a SLA surface: A prospective cohort study in 177 fully and partially edentulous patients. Clin. Oral Implants Res. 2015;26:1121–1128. doi: 10.1111/clr.12499.
    1. French D., Grandin H.M., Ofec R. Retrospective cohort study of 4,591 dental implants: Analysis of risk indicators for bone loss and prevalence of peri-implant mucositis and peri-implantitis. J. Periodontol. 2019;90:691–700. doi: 10.1002/JPER.18-0236.
    1. Heitz-Mayfield L.J.A., Salvi G.E. Peri-implant mucositis. J. Clin. Periodontol. 2018;45((Suppl. S20)):S237–S245. doi: 10.1111/jcpe.12953.
    1. Alassy H., Parachuru P., Wolff L. Peri-Implantitis Diagnosis and Prognosis Using Biomarkers in Peri-Implant Crevicular Fluid: A Narrative Review. Diagnostics. 2019;9:214. doi: 10.3390/diagnostics9040214.
    1. Araujo M.G., Lindhe J. Peri-implant health. J. Clin. Periodontol. 2018;45((Suppl. S20)):S230–S236. doi: 10.1111/jcpe.12952.
    1. Heitz-Mayfield L.J.A. Peri-implant diseases: Diagnosis and risk indicators. J. Clin. Periodontol. 2008;35((Suppl. 8)):292–304. doi: 10.1111/j.1600-051X.2008.01275.x.
    1. Heitz-Mayfield L.J.A., Mombelli A. The Therapy of Peri-implantitis: A Systematic Review. Int. J. Oral Maxillofac. Implant. 2014;29:325–345. doi: 10.11607/jomi.2014suppl.g5.3.
    1. Cieplik F., Deng D., Crielaard W., Buchalla W., Hellwig E., Al-Ahmad A., Maisch T. Antimicrobial photodynamic therapy—What we know and what we don’t. Crit. Rev. Microbiol. 2018;44:571–589. doi: 10.1080/1040841X.2018.1467876.
    1. De Sousa D.L., Lima R.A., Zanin I.C., Klein M.I., Janal M.N., Duarte S. Effect of Twice-Daily Blue Light Treatment on Matrix-Rich Biofilm Development. PLoS ONE. 2015;10:e0131941. doi: 10.1371/journal.pone.0131941.
    1. Konopka K., Goslinski T. Photodynamic Therapy in Dentistry. J. Dent. Res. 2007;86:694–707. doi: 10.1177/154405910708600803.
    1. Wang Y., Wang Y., Wang Y., Murray C.K., Hamblin M.R., Hooper D.C., Dai T. Antimicrobial blue light inactivation of pathogenic microbes: State of the art. Drug Resist. Updat. 2017;33–35:1–22. doi: 10.1016/j.drup.2017.10.002.
    1. Zhang Y., Zhu Y., Chen J., Wang Y., Sherwood M.E., Murray C.K., Vrahas M.S., Hooper D.C., Hamblin M.R., Dai T. Antimicrobial blue light inactivation ofCandida albicans:In vitroandin vivostudies. Virulence. 2016;7:536–545. doi: 10.1080/21505594.2016.1155015.
    1. Sculean A., Deppe H., Miron R., Schwarz F., Romanos G., Cosgarea R. Effectiveness of photodynamic therapy in the treatment of periodontal and peri-implant diseases. Oral Biofilms. 2021;29:133–143. doi: 10.1159/000510189.
    1. Alander J.T., Kaartinen I., Laakso A., Pätilä T., Spillmann T., Tuchin V., Venermo M., Välisuo P. A Review of Indocyanine Green Fluorescent Imaging in Surgery. Int. J. Biomed. Imaging. 2012;2012:1–26. doi: 10.1155/2012/940585.
    1. Courval A., Harmouche L., Mathieu A., Petit C., Huck O., Séverac F., Davideau J.-L. Impact of Molar Furcations on Photodynamic Therapy Outcomes: A 6-Month Split-Mouth Randomized Clinical Trial. Int. J. Environ. Res. Public Health. 2020;17:4162. doi: 10.3390/ijerph17114162.
    1. Nikinmaa S., Alapulli H., Auvinen P., Vaara M., Rantala J., Kankuri E., Sorsa T., Meurman J., Pätilä T. Dual-light photodynamic therapy administered daily provides a sustained antibacterial effect on biofilm and prevents Streptococcus mutans adaptation. PLoS ONE. 2020;15:e0232775. doi: 10.1371/journal.pone.0232775.
    1. Yoshida A., Sasaki H., Toyama T., Araki M., Fujioka J., Tsukiyama K., Hamada N., Yoshino F. Antimicrobial effect of blue light using Porphyromonas gingivalis pigment. Sci. Rep. 2017;7:5225. doi: 10.1038/s41598-017-05706-1.
    1. Nikinmaa S., Podonyi A., Raivio P., Meurman J., Sorsa T., Rantala J., Kankuri E., Tauriainen T., Pätilä T. Daily Administered Dual-Light Photodynamic Therapy Provides a Sustained Antibacterial Effect on Staphylococcus Aureus. Antibiotics. 2021;10:1240. doi: 10.3390/antibiotics10101240.
    1. Hentilä J., Laakamaa N., Sorsa T., Meurman J., Välimaa H., Nikinmaa S., Kankuri E., Tauriainen T., Pätilä T. Dual-Light Photodynamic Therapy Effectively Eliminates Streptococcus Oralis Biofilms. J. Pharm. Pharm. Sci. 2021;24:484–487. doi: 10.18433/jpps32084.
    1. Heikkinen A.M., Räisänen I.T., Tervahartiala T., Sorsa T. Cross-sectional analysis of risk factors for subclinical periodontitis; active matrix metalloproteinase-8 as a potential indicator in initial periodontitis in adolescents. J. Periodontol. 2018;90:484–492. doi: 10.1002/JPER.18-0450.
    1. Lähteenmäki H., Umeizudike K.A., Heikkinen A.M., Räisänen I.T., Rathnayake N., Johannsen G., Tervahartiala T., Nwhator S.O., Sorsa T. aMMP-8 Point-of-Care/Chairside Oral Fluid Technology as a Rapid, Non-Invasive Tool for Periodontitis and Peri-Implantitis Screening in a Medical Care Setting. Diagnostics. 2020;10:562. doi: 10.3390/diagnostics10080562.
    1. Lee W., Aitken S., Sodek J., McCulloch C.A.G. Evidence of a direct relationship between neutrophil collagenase activity and periodontal tissue destruction in vivo: Role of active enzyme in human periodontitis. J. Periodontal Res. 1995;30:23–33. doi: 10.1111/j.1600-0765.1995.tb01249.x.
    1. Mancini S., Romanelli R., Laschinger C.A., Overall C.M., Sodek J., McCulloch C.A. Assessment of a Novel Screening Test for Neutrophil Collagenase Activity in the Diagnosis of Periodontal Diseases. J. Periodontol. 1999;70:1292–1302. doi: 10.1902/jop.1999.70.11.1292.
    1. Räisänen I.T., Heikkinen A.M., Siren E., Tervahartiala T., Gieselmann D.-R., Van Der Schoor G.-J., Van Der Schoor P., Sorsa T. Point-of-Care/Chairside aMMP-8 Analytics of Periodontal Diseases’ Activity and Episodic Progression. Diagnostics. 2018;8:74. doi: 10.3390/diagnostics8040074.
    1. Räisänen I.T., Sorsa T., Van Der Schoor G.-J., Tervahartiala T., Van Der Schoor P., Gieselmann D.-R., Heikkinen A.M. Active Matrix Metalloproteinase-8 Point-of-Care (PoC)/Chairside Mouthrinse Test vs. Bleeding on Probing in Diagnosing Subclinical Periodontitis in Adolescents. Diagnostics. 2019;9:34. doi: 10.3390/diagnostics9010034.
    1. Räisänen I.T., Umeizudike K.A., Pärnänen P., Heikkilä P., Tervahartiala T., Nwhator S.O., Grigoriadis A., Sakellari D., Sorsa T. Periodontal disease and targeted prevention using aMMP-8 point-of-care oral fluid analytics in the COVID-19 era. Med. Hypotheses. 2020;144:110276. doi: 10.1016/j.mehy.2020.110276.
    1. Sorsa T., Tjäderhane L., Salo T. Matrix metalloproteinases (MMPs) in oral diseases. Oral Dis. 2004;10:311–318. doi: 10.1111/j.1601-0825.2004.01038.x.
    1. Sorsa T., Gieselmann D., Arweiler N.B., Hernández M. A quantitative point-of-care test for periodontal and dental peri-implant diseases. Nat. Rev. Dis. Prim. 2017;3:17069. doi: 10.1038/nrdp.2017.69.
    1. Sorsa T., Alassiri S., Grigoriadis A., Räisänen I.T., Pärnänen P., Nwhator S.O., Gieselmann D.-R., Sakellari D. Active MMP-8 (aMMP-8) as a Grading and Staging Biomarker in the Periodontitis Classification. Diagnostics. 2020;10:61. doi: 10.3390/diagnostics10020061.
    1. Sorsa T., Tjäderhane L., Konttinen Y.T., Lauhio A., Salo T., Lee H., Golub L.M., Brown D.L., Mäntylä P. Matrix metalloproteinases: Contribution to pathogenesis, diagnosis and treatment of periodontal inflammation. Ann. Med. 2006;38:306–321. doi: 10.1080/07853890600800103.
    1. Sorsa T., Gursoy U.K., Nwhator S., Hernández M., Tervahartiala T., Leppilahti J., Gürsoy M., Könönen E., Emingil G., Pussinen P., et al. Analysis of matrix metalloproteinases, especially MMP-8, in gingival crevicular fluid, mouthrinse and saliva for monitoring periodontal diseases. Periodontology. 2015;70:142–163. doi: 10.1111/prd.12101.
    1. Golub L.M., Räisänen I.T., Sorsa T., Preshaw P.M. An Unexplored Pharmacologic/Diagnostic Strategy for Peri-Implantitis: A Protocol Proposal. Diagnostics. 2020;10:1050. doi: 10.3390/diagnostics10121050.
    1. Renvert S., Persson G.R., Pirih F.Q., Camargo P.M. Peri-implant health, peri-implant mucositis, and peri-implantitis: Case definitions and diagnostic considerations. J. Clin. Periodontol. 2018;45:S278–S285. doi: 10.1111/jcpe.12956.
    1. Berglundh T., Armitage G., Araujo M.G., Avila-Ortiz G., Blanco J., Camargo P.M., Chen S., Cochran D., Derks J., Figuero E., et al. Peri-implant diseases and conditions: Consensus report of workgroup 4 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J. Clin. Periodontol. 2018;45((Suppl. S20)):S286–S291. doi: 10.1111/jcpe.12957.
    1. Heitz-Mayfield L.J.A., Heitz F., Lang N.P. Implant Disease Risk Assessment IDRA–a tool for preventing peri-implant disease. Clin. Oral Implant. Res. 2020;31:397–403. doi: 10.1111/clr.13585.
    1. Mishler O.P., Shiau H.J. Management of Peri-implant Disease: A Current Appraisal. J. Evid. Based Dent. Pr. 2014;14:53–59. doi: 10.1016/j.jebdp.2014.04.010.
    1. Liu S., Limiñana-Cañal J., Yu J. Does chlorhexidine improve outcomes in non-surgical management of peri-implant mucositis or peri-implantitis? A systematic review and meta-analysis. Medicina Oral, Patología Oral Y Cirugía Bucal. 2020;25:e608–e615. doi: 10.4317/medoral.23633.
    1. Al-Majid A., Alassiri S., Rathnayake N., Tervahartiala T., Gieselmann D.-R., Sorsa T. Matrix Metalloproteinase-8 as an Inflammatory and Prevention Biomarker in Periodontal and Peri-Implant Diseases. Int. J. Dent. 2018;2018:1–27. doi: 10.1155/2018/7891323.
    1. Hashim D., Cionca N., Combescure C., Mombelli A. The diagnosis of peri-implantitis: A systematic review on the predictive value of bleeding on probing. Clin. Oral Implant. Res. 2018;29((Suppl. S16)):276–293. doi: 10.1111/clr.13127.
    1. Lupi S.M., Redoglia L., Baena A.R.Y., Garbelli G., Baena R.R.Y. Detection of peri-implant inflammation by the use of a matrix metalloproteinase-8 chair-side test. Minerva Stomatol. 2019;68:168–176. doi: 10.23736/S0026-4970.19.04149-9.
    1. Tavares A., Carvalho C.M.B., Faustino M.A., Neves M.G.P.M.S., Tomé J.P.C., Tomé A.C., Cavaleiro J.A.S., Cunha Â., Gomes N.C.M., Alves E., et al. Antimicrobial Photodynamic Therapy: Study of Bacterial Recovery Viability and Potential Development of Resistance after Treatment. Mar. Drugs. 2010;8:91–105. doi: 10.3390/md8010091.
    1. Lang N.P., Adler R., Joss A., Nyman S. Absence of bleeding on probing an indicator of periodontal stability. J. Clin. Periodontol. 1990;17:714–721. doi: 10.1111/j.1600-051X.1990.tb01059.x.
    1. Nikinmaa S., Moilanen N., Sorsa T., Rantala J., Alapulli H., Kotiranta A., Auvinen P., Kankuri E., Meurman J., Pätilä T. Indocyanine Green-Assisted and LED-Light-Activated Antibacterial Photodynamic Therapy Reduces Dental Plaque. Dent. J. 2021;9:52. doi: 10.3390/dj9050052.
    1. Mylona V., Anagnostaki E., Parker S., Cronshaw M., Lynch E., Grootveld M. Laser-Assisted aPDT Protocols in Randomized Controlled Clinical Trials in Dentistry: A Systematic Review. Dent. J. 2020;8:107. doi: 10.3390/dj8030107.
    1. Monzavi A., Chinipardaz Z., Mousavi M., Fekrazad R., Moslemi N., Azaripour A., Bagherpasand O., Chiniforush N. Antimicrobial photodynamic therapy using diode laser activated indocyanine green as an adjunct in the treatment of chronic periodontitis: A randomized clinical trial. Photodiagnosis Photodyn. Ther. 2016;14:93–97. doi: 10.1016/j.pdpdt.2016.02.007.
    1. Kura S., Viswa C.R., Amarender R.A., Harish R.B., Chakravarthy R., Anumala N. Effect of a single session of antimicrobial photodynamic therapy using indocyanine green in the treatment of chronic periodontitis: A randomized controlled pilot trial. Quintessence Int. 2015;46:391–400. doi: 10.3290/J.QI.A33532.
    1. Herrera D. Insufficient evidence for photodynamic therapy use in periodontitis. Evid. -Based Dent. 2011;12:46. doi: 10.1038/sj.ebd.6400791.
    1. Antczak-Bouckoms A.A., Tulloch J.F.C., Berkey C.S. Split-mouth and cross-over designs in dental research. J. Clin. Periodontol. 1990;17:446–453. doi: 10.1111/j.1600-051X.1990.tb02343.x.
    1. Moy P.K., Medina D., Shetty V., Aghaloo T.L. Dental implant failure rates and associated risk factors. Int. J. Oral Maxillofac. Implant. 2005;20:569–577.
    1. Elani H.W., Starr J.R., Da Silva J.D., Gallucci G.O. Trends in Dental Implant Use in the U.S., 1999–2016, and Projections to 2026. J. Dent. Res. 2018;97:1424–1430. doi: 10.1177/0022034518792567.
    1. Monje A., Catena A., Borgnakke W.S. Association between diabetes mellitus/hyperglycaemia and peri-implant diseases: Systematic review and meta-analysis. J. Clin. Periodontol. 2017;44:636–648. doi: 10.1111/jcpe.12724.
    1. Derks J., Tomasi C. Peri-implant health and disease. A systematic review of current epidemiology. J. Clin. Periodontol. 2015;42:S158–S171. doi: 10.1111/jcpe.12334.

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