Secondary Logo

Journal Logo

Basic and Clinical Research

Photodynamic Therapy to Treat Periimplantitis

Bombeccari, Gian Paolo DDS; Guzzi, Gianpaolo DDS; Gualini, Federico MD, DDS; Gualini, Sara DDS; Santoro, Franco MD, DDS; Spadari, Francesco MD, DDS

Author Information
doi: 10.1097/01.id.0000433592.18679.91
  • Free

Abstract

Periimplantitis is a chronic infectious disease that can affect periimplant tissues such as gingiva and supporting bone, compromising the osseointegration prognosis. The condition is characterized by acute episodes of periimplant tissue destruction alternated with periods of relative dormancy.1 The causal relationship between a persisting biofilm on implant surfaces and the occurrence of periimplant inflammation has been detected clinically.1 Pathogen microflora induced periodontal disease may also favor the development of periimplantitis.2 The presence of biofilm-associated microorganisms may lead to an increased resistance antimicrobial treatment, in which antibiotics might fail to kill bacteria adhering on dental titanium implant surfaces.3 With regard to the implant rough surface, it has been reported that the cleaning might be very difficult to perform because bacteria are protected in microirregularities or undercuts of the surface.4

However, there is limited evidence available that such treatment with adjunctive use of systemic antibiotics could resolve periimplantitis lesions.5,6 In recent years, the antimicrobial activity and efficacy of laser light, which depends on its photothermic effects, have been described both in vitro and in vivo by several authors.7–10 Microbiological studies in periodontology have shown that diode laser can significantly reduce the periodontopathogenic bacteria.11Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans (formerly Actinobacillus actinomycetemcomitans) are the most frequent pathogenic bacteria studied together with lethal photosensitization.10–12

Photodynamic therapy (PDT) is based on the use of low-power laser with appropriate wavelength to kill10–13 cells and/or microorganisms, involving patients previously treated with photosensitizer such as toluidine blue O (TBO), which is capable of binding to the targeted cells. The activated photosensitizer by the light reacts with the substrate, therefore producing highly reactive oxygen agents such as free radicals and/or singlet oxygen, which are toxic for the microorganisms.10 PDT has been reported as an alternative approach in implant surface detoxification.10,12 Assuming that pathogens associated with periimplantitis are protected by biofilm-producing bacteria,13 which are able to colonize in particular rough structures such as the surface of implants,14 it is clear that, to achieve the eradication of bacteria in biofilms, the antimicrobial agents have to be overdosed up to 10 times.15,16 In this way, the risks and benefits of antibiotic therapy may not be as favorable as we think; therefore, we sought to investigate the efficacy and safety of PDT in the treatment of periimplant disease. The aim of this clinical prospective study was to compare conventional periimplantitis treatment (scaling and chlorhexidine irrigation after raising a mucoperiosteal flap) with PDT (to eliminate and to remove bacteria associated with periimplantitis from the implant surfaces).

Materials and Methods

Patients and Study Design

A total of 40 Caucasian patients (24 women and 16 men) with a mean age of 46 years (range, 33–64 years) being previously clinically and radiographically diagnosed as having periimplantitis around at 1 or more dental implant. Diseased implants were considered as having a probing pocket depth (PPD) measurement ≥5 mm, with the presence of bleeding on probing (BOP) and/or inflammatory exudation. Patients also had concomitant radiographic signs of progressive bone loss (bone loss >3 threads) around the dental implant since at least 12 months. Patients were randomly divided by a random assignment into 2 treatment groups: a conventional therapy group and a PDT group. In each group, we collected clinical parameters of periodontal status by distinguishing between periodontally healthy persons and periodontally compromised persons. The clinical study was performed by 2 clinicians (Clinician-1 [Cl-1] and Clinician-2 [Cl-2]). Clinical data were recorded and collected by Cl-1. Surgical treatment of patients with periimplantitis was carried out by Cl-2. All the eligible patients had earlier been rehabilitated by titanium dental implants having rough surfaces (Nobel Biocare; Nobel Biocare Services AG; Zürich, Switzerland).

Exclusion criteria were antibiotic administration during the previous 3-month period before the sampling, heavy smokers (>10 cigarettes per day), heavy alcohol consumers, patients undergoing head and neck chemoradiotherapy, degenerative bone diseases, chronic inflammatory oral diseases on immunological basis, and immediate postextraction implant placement. Local ethical committee approval was obtained by the institutional board. The purpose and design of the study were explained and all patients signed informed consent forms.

Clinical Assessment

Clinical data were collected before treatment, at the baseline, as well as at follow-up examinations after 3 and 6 months by one and the same examiner (CL-1), who was not aware of the random allocation of the patients with respect to treatment assignment. The variables recorded in 4 positions around the affected implants were PPD, probing attachment levels (PAL), BOP, and inflammatory exudation (IE) sampling on probing.

The BOP and IE were recorded as either absent (0) or present (1). Measurements of PPD and PAL were performed using a plastic constant pressure probe with a 20 g controlled probing force (PDT sensor probe; Pro-Dentex, Batesville, AR).

Surgical Procedure

In all patients, microbial samples of periimplant pockets were taken before the open flap surgery was performed. Three sterile paper strips were inserted (inline sterilized hand-rolled point; B.M. Dentale, Torino, Italy) and left in place for 10 seconds and then removed. Full-thickness flaps were elevated to remove the periimplant granulation tissues and to expose the implant surface. In the conventional therapy group, the implant surfaces were then curetted with plastic scalers (Have implant-recall-set, Kerr, Italy) and irrigated with a 0.2% chlorhexidine digluconate solution for 1 minute before treatment.

In the PDT group, after curettage following the same modality of conventional therapy group, the TBO substance (100 µg/mL) was applied inside the periimplant pocket by a thin needle and was left in place for 1 minute. All surpluses of TBO were removed by the paper pellets. The stained area was then irradiated with a diode laser, having a wavelength of 810 nm and a continuous wave mode of 1 W, together with 300-μm wave guide fiber for 20 seconds (Doctor Smile Laser D5; Lambda Scientifica SPA, Vicenza, Italy). The irradiation was directed along the surfaces of the periimplant defect. The procedure was repeated 5 times, with a 30-second pause in between PDT for a total exposure time of 100 seconds. Finally, saline solution was sprinkled over the exposed area to remove the photosensitizer from the periimplant pockets. The mucosal flaps were sutured back into position using a 3-0 non-absorbable silk fiber (ETHICON, Inc., Johnson & Johnson, Cincinnati, OH). In both patients groups, immediately after the decontamination treatments, a second microbial sample was obtained from each treated titanium dental implant.

Four paper strips were then collected from each sample of the periimplant defect site and directly placed thereafter in 1100-µL vials containing anaerobic reduced transport medium (BBL Port-A-Cul; Becton Dickinson and Company Italia, Buccinasco, Milan, Italy). All samples were gathered by the same operator and coded by an assistant to mask the identification of the samples. After treatment, all patients were instructed to rinse with an aqueous solution containing 0.2% chlorhexidine (10 mL for 1 minute at an interval of 8 hours for 2 weeks).

Culture Methods

The paper strips were analyzed within 24 hours. They were then centrifuged for 30 seconds, they were serially diluted 10-folded in peptonated water ranging from 10−1 and 10−6 for quantitative evaluation of colony forming units (CFU) per milliliter and to obtain isolated colonies for qualitative assay. Aliquots of 0.1 mL of the dilutions were plated onto enriched trypticase soy-agar (ETSA) and trypticase soy-serum bacitracin vancomycin (TSVB), according to standardized manners.17 The ETSA plates were then incubated in anaerobic jars filled by mixed gas atmosphere (85% N2, 10% H2, 5% CO2) at 37°C for 7 days, using the evacuation replacement method.

The TSVB agar plates were incubated in a 5% CO2 atmosphere for 7 days and at 37°C. The bacterial identification was performed on the basis of Gram staining, aero tolerance, colony morphology, nitrate reduction, positive catalase reaction, indole production, esculin hydrolysis, α-glucosidase activity, hydrolysis, oxidase, and N-benzoil-DL-arginine-2-naphthylamide.18 Total anaerobic viable counts and cultivable microbiota detections of P. gingivalis, P. intermedia, and A. actinomycetemcomitans were obtained by Gram staining, colony morphology, and positive catalase tests.

Statistical Analysis

Statistical analysis was performed using commercially available software (SPSSII; SPSS, Inc., Chicago, IL). Total viable counts, for each dental implant, were transformed into CFU per milliliter by predetermined conversion factors to account for dilution and size of the evaluated plate surface. Differences between bacterial species and patient groups were assessed by Student t test.

Mean and SD values (mean ± SD) were calculated for each treatment. The same variance and normal distribution of the groups at issue was assumed. The paired t test was used to compare the data from baseline to those at 3 and 6 months for each treatment group. Clinical parameters (probing pocket depth, PALs, BOP, and IE) from PDT and conventional therapy groups were compared by 2-tailed t test. The chi-square test was used to compare between the groups. Differences were considered statistically significant when P < 0.05.

Results

The PDT group consisted of 14 periodontally compromised patients and 6 periodontally healthy patients, whereas 12 periodontally compromised patients and 8 periodontally healthy patients were observed in the conventional therapy group. Total anaerobic bacterial count samples were taken before and after treatment are shown in Table 1.

Table 1
Table 1:
Total Anaerobia Bacterial Counts at Various Microbial Sampling Times, and Bacteria Reduction Percentage Immediately After Treatment for Each Patient, Relating to the Baseline Counts

Before treatment, the mean counts of 3 bacterial species (P. gingivalis, P. intermedia, and A. actinomycetemcomitans) were substantially equal for both treatment groups (P = 0.82). The comparative data of the posttreatment analyses did not show a significant reduction in the total bacterial counts (Table 1). The PDT intervention was able to reduce the bacterial biofilm of 95.2% CFU per milliliters, on average, whereas the conventional therapy modality resulted in an average CFU per milliliters reduction of 80.85% (P = 0.11). Porphyromonasgingivalis and P. intermedia were detected in all the samples that were taken before to the treatment. Detection of A. actinomycetemcomitans was positive with the following distribution: 15 patients of the PDT group (15 out of 20) and 16 patients of the conventional therapy group (16 of 20). A reduction by 2 log steps (reduction of bacterial count by 2 log steps) was reached, respectively, in 2 samples of P. gingivalis and 1 sample of A. actinomycetemcomitans in the PDT group.

In the PDT group, A. actinomycetemcomitans showed a statistically significant reduction in bacterial count, after treatment, in comparison with the conventional therapy group (P = 0.01) (Table 2). Observations obtained at the 12th and 24th weeks posttreatment examination showed a slight-partial increase of the anaerobic bacterial counts (Table 1). As to the clinical parameters, at the 24th week observation, a 30% (60% at baseline) of periimplant sites treated according to the conventional therapy modality showed signs of IE as a clinical relapse of the acute phase, as well as 50% of periimplant defects of the same group displayed signs of BOP (80% at baseline). However, 10% (70% at baseline) of periimplant sites of patients treated by PDT displayed very few cases with signs of BOP (P = 0.02) and in the absence of IE (P = 0.001). The decrease in IE index in the PDT group in comparison with the conventional therapy group was resulted statistically significant (P = 0.03) (Table 3).

Table 2
Table 2:
Comparative Data Specific-Specie of Anaerobic Bacteria, Analyzed Between PDT and CT Treatment
Table 3
Table 3:
Change in Clinical Parameters by Treatment

Interestingly, the prevalence of BOP and IE at 6 months after treatment was observed in adult periodontally compromised patients in both groups. Changes in PPD were recorded in the PDT group only, with statistically significant difference between baseline and the 24th week observation. In the PDT group, the mean 6-month change of PPD was made up for 1 ± 0.31 mm (P = 0.008). Moreover, statistically significant differences in terms of PPD reduction were found between the 2 treatment protocols during the follow-up period (P = 0.02) (Table 3).

Discussion

The outcomes of this study indicate that both PDT and conventional therapy resulted in a high reduction percentage of anaerobic bacterial with regard to the total initial bacterial count (PDT, 95.2%; conventional therapy, 80.85%). However, the comparative data not seem to be statistically significant. The set of diode laser parameters that we used was established on the basis of results previously obtained in a study of Sennhenn-Kirchner et al13 on aerobic bacteria decontamination of rough dental titanium surfaces. In such a study, an average reduction was reported in CFU of aerobic bacteria rates of almost 100%.13 However, in general, cocci colonization usually predominates at the beginning of a biofilm formation.19 In an in vitro study of Hass et al,20 differences were not seen between reduction of black pigmented bacteria and A. actinomycetemcomitans, in which all periodontal pathogens had been eradicated by the PDT method associated with TBO. It is well known that the results of in vitro or animal studies cannot always be directly extrapolated to the human situation; therefore, they need to be interpreted with caution. Among the main factors that may interfere with the effectiveness of PDT in clinical application, there is the light distribution on the target area. On the threaded implant, not all areas are accessible in the same intensity by laser beam irradiation due to the threads. The morphology of the periimplant bone defect and the unidirectional activity of the laser beam are not enabled to uniformly apply the light to the implant surface at the optimal angle of 90 degree.13 The findings are consistent with the results of the in vivo study by Dörtbudak et al,10 although the type of implants, the laser wavelength (690 nm), and used parameters were different to ours in that report. In this work, a significant mean reduction of A. actinomycetemcomitans has been observed, relatively to the higher presence of positive samples, if compared with the expected averages. However, a 2 log step bacterial count reduction has been reached in only 3 bacteria samples, reflecting the complexity of the role of environmental variability (in vivo) in the titanium dental implant decontamination process. The detection data of A. actinomycetemcomitans in periimplantitis are contradictory. Variables such as periodontal status in partially edentulous patients, pocket's depth, pus formation, implant configuration, and surface can play a crucial role as a microbial reservoir by determining the composition of the microflora around the implants.1–3 Furthermore, the microbiological techniques used for the analyses, culture, DNA, and immunoblot assay can influence the results in the detection frequency of pathogenic species.21 In this study, the prevalence of periodontally compromised patients and the type of dental implant surface could explain the percentage of implant sites with detectable A. actinomycetemcomitans. However, a 2 log step bacterial count reduction has been reached in only 3 bacteria samples, as to prove the role of environmental variability in the titanium dental implant decontamination process in vivo. The microaerophyl metabolism and intracellular invasion properties of A. actinomycetemcomitans might play a role in microbial identification sampling or to get up decontamination results by PDT treatments.22

The lower rate of re-colonization of pathogenic microorganisms at the 12th and 24th week observations in the PDT group versus the conventional therapy group might contribute to reach the best control of clinical inflammatory parameters observed at 6 months. In fact, the simple presence of pathogens at periimplant sites does not necessarily imply a periimplantitis if the levels of microorganisms are kept at low levels.23 Furthermore, the results of this study are not directly comparable to those of other in vivo studies, evaluating the maintenance of the microbiological effects at 3 and 6 months posttreatment in periimplantitis therapy. Potential variables can be considered, such as the different persistence of the chlorhexidine (CHX) 0.2% on the rough titanium surface with respect to the smooth type. The higher levels of adsorption on the rough surfaces associated with slow release of CHX can influence the postoperative pathogens accumulation.24 Thus, it is important to emphasize the necessity of controlling the quality of patient's oral hygiene care, reducing the number of microorganisms at periimplant sites.

This holds true specifically in relation to the progression of periimplantitis lesions at type D roughness implants (Ti-Unite implant surfaces, Ti-Unite, Nobel Biocare-Service AG; Zurich-Airport, Switzerland).25 The statistically significant reduction of BOP, IE, and PPD in the PDT group at the 24th week observation further indicates that the PDT therapy may positively influence several processes associated with tissue repair, in agreement with the findings of a recent meta-analysis.26 Likewise, in a recent controlled clinical trial, a beneficial effect on gingival inflammation, indicated by a significant decrease in the volume of gingival crevicular fluid, was also demonstrated when low-level laser had been used as adjunct therapy in the treatment of periodontal inflammation.27 A similar BOP index reduction, as revealed in this study, has been reported on a randomized controlled clinical trial, about the possible additional improvements of the clinical parameters induced by PDT, as adjunct to nonsurgical periodontal treatment.28 It has been suggested that PDT as adjunct to the nonsurgical periodontal treatment should be performed repeatedly during the 1st week of healing to enhance the antimicrobial effects.28

Within the framework of this study, whose design was based on surgical treatment with open flap, a single stage application of PDT was performed to avoid discrepancies (ie, confounding effects of various frequencies of treatment) in both the groups. The greater prevalence of BOP and IE in periimplant defects of periodontally compromised patients with respect to periodontally healthy patients with regard to the 2 treatment groups suggests that patients who carry periodontopathic bacteria are more at risk to develop an acute phase of periimplant disease, in accordance with the outcomes reported recently in literature.29,30 To the best of our knowledge, this study did investigated for the 1st time the clinical and microbiological effects of the PDT in vivo in the decontamination of rough implant surfaces in areas affected by periimplantitis. However, additional comparative in vivo studies are warranted to draw definitive conclusions about the possible clinical and antimicrobial benefit of PDT procedure used in treatment of periimplantitis. Such studies will be needed to examine the influence of more oral environmental variables on PDT outcomes, before any long-term effect of the procedure can be presented.

Conclusion

The present investigation failed to demonstrate that the treatment effect of periimplant lesions with PDT plus TBO by the diode laser technique may lead to a routinely substantial decontamination of anaerobic bacteria on rough titanium implant surfaces, as compared with the conventional surgical treatment. However, PDT seems to distinctly reduce the clinical signs of periimplant inflammation, resulting in a significant reduction of the bleeding scores and inflammatory exudates with respect to the conventional surgical approach.

Disclosure

The authors claim to have no financial interest, either directly or indirectly, in the products or information listed in the article.

Acknowledgments

G. P. Bombeccari conceived and designed the clinical study. F. Gualini and S. Gualini performed the clinical study. G. P. Bombeccari analyzed the data and performed the statistical analysis. G. P. Bombeccari wrote the paper. G. Guzzi reviewed and edited the paper. F. Santoro and F. Spadari supervised the study project.

References

1. Mombelli A, Lang NP. The diagnosis and treatment of peri-implantitis. Periodontol 2000. 1998;17:63–76.
2. Leonhardt A, Dahlén G, Renvert S. Five-year clinical, microbiological, and radiological outcome following treatment of peri-implantitis in man. J Periodontol. 2003;74:1415–1422.
3. Sbordone L, Bortolaia C. Oral microbial biofilms and plaque-related diseases: Microbial communities and their role in the shift from oral health to disease. Clin Oral Investig. 2003;7:181–188.
4. Esposito M, Hirsch J, Lekholm U, et al.. Differential diagnosis and treatment strategies for biologic complications and failing oral implants: A review of the literature. Int J Oral Maxillofac Implants. 1999;14:473–490.
5. Klinge B, Gustafsson A, Berglundh T. A systematic review of the effect of anti-infective therapy in the treatment of peri-implantitis. J Clin Periodontol. 2002;29(suppl 3):213–225.
6. Lindhe J, Meyle J; Group D of European Workshop on Periodontology. Peri-implant diseases: Consensus report of the sixth European workshop on periodontology. J Clin Periodontol. 2008;35:282–285.
7. Romanos GE, Henze M, Banihashemi S, et al.. Removal of epithelium in periodontal pockets following diode (980 nm) laser application in the animal model: An in vitro study. Photomed Laser Surg. 2004;22:177–183.
8. Kreisler M, Kohnen W, Marinello C, et al.. Antimicrobial efficacy of semiconductor laser irradiation on implant surfaces. Int J Oral Maxillofac Implants. 2003;18:706–711.
9. Deppe H, Horch HH, Henke J, et al.. Peri-implant care of ailing implants with the carbon dioxide laser. Int J Oral Maxillofac Implants. 2001;16:659–667.
10. Dörtbudak O, Haas R, Bernhart T, et al.. Lethal photosensitization for decontamination of implant surfaces in the treatment of peri-implantitis. Clin Oral Implants Res. 2001;12:104–108.
11. Moritz A, Schoop U, Goharkhay K, et al.. Treatment of periodontal pockets with a diode laser. Lasers Surg Med. 1998;22:302–311.
12. Hayek RR, Araújo NS, Gioso MA, et al.. Comparative study between the effects of photodynamic therapy and conventional therapy on microbial reduction in ligature-induced peri-implantitis in dogs. J Periodontol. 2005;76:1275–1281.
13. Sennhenn-Kirchner S, Klaue S, Wolff N, et al.. Decontamination of rough titanium surfaces with diode lasers: Microbiological findings on in vivo grown biofilms. Clin Oral Implants Res. 2007;18:126–132.
14. Hultin M, Gustafsson A, Hallström H, et al.. Microbiological findings and host response in patients with peri-implantitis. Clin Oral Implants Res. 2002;13:349–358.
15. Groessner-Schreiber B, Hannig M, Dück A, et al.. Do different implant surfaces exposed in the oral cavity of humans show different biofilm compositions and activities? Eur J Oral Sci. 2004;112:516–522.
16. Socransky SS, Haffajee AD. Dental biofilms: Difficult therapeutic targets. Periodontol 2000. 2002;28:12–55.
17. Laughon BE, Syed SA, Loesche WJ. Rapid identification of Bacteroides gingivalis. J Clin Microbiol. 1982;15:345–346.
18. Gusberti FA, Syed SA. Development of a miniaturized nitrate reduction test for the identification of oral bacteria. J Microbiol Methods. 1984;2:333–338.
19. Leonhardt A, Bergström C, Lekholm U. Microbiologic diagnostics at titanium implants. Clin Implant Dent Relat Res. 2003;5:226–232.
20. Haas R, Dörtbudak O, Mensdorff-Pouilly N, et al.. Elimination of bacteria on different implant surfaces through photosensitization and soft laser. An in vitro study. Clin Oral Implants Res. 1997;8:249–254.
21. Quirynen M, De Soete M, van Steenberghe D. Infectious risks for oral implant: A review of the literature. Clin Oral Implants Res. 2002;13:1–19.
22. Fives-Taylor P, Meyer D, Mintz K. Characteristics of Actinobacillus actinomycetemcomitans invasion of and adhesion to cultured epithelial cells. Adv Dent Res. 1995;9:55–62.
23. Heydenrijk K, Meijer HJ, van der Reijden WA, et al.. Microbiota around root-form endosseous implants: A review of the literature. Int J Oral Maxillofac Implants. 2002;17:829–838.
24. Kozlovsky A, Artzi Z, Moses O, et al.. Interaction of chlorhexidine with smooth and rough types of titanium surfaces. J Periodontol. 2006;77:1194–1200.
25. Albouy JP, Abrahamsson I, Persson LG, et al.. Spontaneous progression of peri-implantitis at different types of implants. An experimental study in dogs. I: Clinical and radiographic observations. Clin Oral Implants Res. 2008;19:997–1002.
26. Woodruff LD, Bounkeo JM, Brannon WM, et al.. The efficacy of laser therapy in wound repair: A meta-analysis of the literature. Photomed Laser Surg. 2004;22:241–247.
27. Qadri T, Miranda L, Tunér J, et al.. The short-term effects of low-level lasers as adjunct therapy in the treatment of periodontal inflammation. J Clin Periodontol. 2005;32:714–719.
28. Chondros P, Nikolidakis D, Christodoulides N, et al.. Photodynamic therapy as adjunct to non-surgical periodontal treatment in patients on periodontal maintenance: A randomized controlled clinical trial. Lasers Med Sci. 2009;24:681–688.
29. Cho-Yan Lee J, Mattheos N, Nixon KC, et al.. Residual periodontal pockets are a risk indicator for peri-implantitis in patients treated for periodontitis. Clin Oral Implants Res. 2012;23:325–333.
30. Roccuzzo M, Bonino F, Aglietta M, et al.. Ten-year results of a three arms prospective cohort study on implants in periodontally compromised patients. Part 2: Clinical results. Clin Oral Implants Res. 2012;23:389–395.
Keywords:

diode laser; periimplantitis; photodynamic therapy; dental implant decontamination; chlorhexidine; periimplantitis therapy

Copyright © 2013 Wolters Kluwer Health, Inc. All rights reserved.