Treatment of peri-implantitis: Fiction or reality? Part 2: Adjuncts and decontamination approaches in the non-surgical and surgical management of peri-implantitis

Peri-implantitis therapy starts with a non-surgical step, followed by re-evaluation and, depending on the outcomes, progress to the surgical step or to supportive peri-implant care (SPIC).¹ An important part of the peri-implantitis treatment pathway is the decontamination of the implant surface.^1,2,3 In terms of clinical outcomes and histological observations, preclinical and clinical studies have reported that no surface decontamination method (e.g. titanium (Ti) curettes, plastic curettes, Ti brushes, air-polishing abrasives, laser application or chemotherapeutic approaches) appears to yield superior outcomes to any other.^4,5,6,7 No significant long-term differences have been found, for instance, between the use of a gauze soaked in saline and other decontamination techniques, such as employing rotating brushes, H₂O₂, air powder abrasives, or citric acid.⁸ However, although no decontamination technique has been found to be the most effective,^9,10 the objective of this article is to present a summary of the evidence for different methods and to try to understand why these techniques might be failing to achieve medium-to long-term (≥3 years) improvement (Table 1). Importantly, current European Federation of Periodontology (EFP) S3 Level Clinical Practice Guidelines (CPG) recommend that implant-supported prostheses, which hinder self-performed oral hygiene, be adjusted prior to the surgical therapy of peri-implantitis. Furthermore, it is suggested that implant-supported prostheses, where feasible, be removed in conjunction with the surgical treatment of peri-implantitis to facilitate access and peri-implant tissue healing.¹

Physical and chemical approaches for decontamination

The effectiveness of specific professional mechanical plaque removal (PMPR) regimens in reducing the risk of recurrent peri-implantitis has not yet been determined. Based on the current EFP S3 CPG, it is suggested that various approaches for dental implant biofilm removal may be employed, either alone or in combination. These approaches may include the use of area-specific curettes, ultrasonic or sonic instruments, rubber cups or brushes, and air-polishing devices equipped with glycine powder or erythritol.¹ Current evidence suggests that the use of air-polishing or Er:YAG laser for implant surface decontamination during the surgical treatment of peri-implantitis should not be employed.¹ Furthermore, the use of Ti brushes may be considered as an alternative or adjunct to standard decontamination methods.¹

The effect of different topical antiseptics, such as sodium hypochlorite (NaOCl 1.0%), hydrogen peroxide (3.0%), chlorhexidine gluconate (0.2%), citric acid (40.0%, pH1), triclosan (0.3%, and alcohol 8.7%), and alcohol-based antimicrobial compounds (menthol, thymol, methyl-salicylate, eucalyptol, alcohol (21.6%)), were evaluated in an in vitro study¹¹ to detect the antimicrobial efficacy against Candida albicans, Streptococcus sanguinis, or Staphylococcus epidermidis attached to machined titanium implant surfaces. Only sodium hypochlorite showed a significant in vitro effect on all three biofilms tested, although the 1.0% concentration used in this in vitro model is not usually used in the mouth without a rubber dam. Barbour et al suggested further work was needed to elucidate the impact of functionalization with chlorhexidine-reduced bacterial coverage on the titanium dioxide layer of implants.¹²

Chlorhexidine has been widely used for the control of dental plaque, as well as for the treatment of gingivitis and periodontitis. Chlorhexidine is a cationic broad-spectrum agent against Gram-positive and -negative bacteria, fungi and some viruses.¹³ The substantivity of chlorhexidine has been attributed to factors such as its cationic nature, the formation of reservoirs in the oral cavity (e.g. teeth, oral mucosa), concentration, time, temperature and pH. As such, the use of chlorhexidine chips (PerioChip, Dexcel Pharma GmbH, Germany), 2.5 mg of chlorhexidine gluconate) following debridement of sites diagnosed with peri-implantitis lesions may be a potential treatment modality, as evidenced by the reduction of probing pocket depth (PPD) (>2 mm) and bleeding on probing (BoP) (ca 50%). However, other clinical studies have failed to find significant effect on the treatment outcomes with the concomitant use of chlorhexidine¹⁴ or hydrogen peroxide.¹⁵ Current guidelines,¹ suggest not to use chlorhexidine for implant surface decontamination during surgical therapy of peri-implantitis.

The antimicrobial activity of six nanoparticulate metal oxides (silver (Ag), cuprous oxide (Cu₂O), cupric oxide (CuO), zinc oxide (ZnO), titanium dioxide (TiO₂), tungsten oxide (WO₃), AgCuO composite and AgZnO composite) were assessed against Prevotella intermedia, Porphyromonas gingivalis, Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans.¹⁶ The study reported that the bacteriostatic and bactericidal activity of the nanoparticles tested in descending order was: Ag >AgCuO >Cu₂O >CuO >AgZnO >ZnO >TiO₂ >WO₃. ZnO demonstrated a significant decrease in growth of all species tested within 4 hours. This study highlighted the potential use of nano-coatings for the treatment of peri-implantitis. However, these in vitro data need clinical study correlation to provide robust conclusions for their use in the treatment for peri-implantitis.

Electrolytic therapy

Recent preclinical and clinical studies, have reported evaluations of the potential effect of an electrolytic method (EC) on the decontamination of implant surfaces in combination with surgical regenerative therapy for the treatment of peri-implantitis.^17,18 In this context, a randomized clinical trial of 24 patients with peri-implantitis, with any type of bone defect, received surgical regenerative therapy of peri-implantitis lesions, using either an electrolytic method (EC) to remove biofilms, or a combination of powder spray and electrolytic method (PEC). There was no statistically significant difference in 6-month outcomes between EC and PEC, particularly in relation to bone gain (2.71 ± 1.70 mm for EC, and 2.81 ± 2.15 mm for PEC). EC of contaminated implants achieved an implant surface where complete re-osseo-integration was reported for 50% of the cases.¹⁸ The 18-month follow-up after therapy demonstrated significant radiographic bone fill and the improvement of clinical parameters – radiological gains in bone, and reductions in PPD, BoP and suppuration were proven and remained stable over an 18-month period.¹⁹

Adjunctive laser therapy

Preclinical studies evaluating the use of carbon dioxide (CO₂), erbium:YAG (Er:YAG), and neodymium-doped:yttrium (Nd:YAG) lasers for the treatment of experimentally induced peri-implantitis have been reported.²⁰ The results are often conflicting and there is a need for longitudinal randomized controlled trials to support the benefit of the use of these lasers.

An in vitro study has demonstrated the bactericidal efficacy of diode lasers (810-nm wavelength Ora Laser 01 IST (Oralia, Konstanz, Germany), and 980-nm wavelength Schütz WDL 2.5 (Schütz Dental Group, Germany) for the reduction of aerobic bacteria colonizing rough titanium samples in biofilms grown intra-orally. This study revealed that the streptococci group was reduced by 99.29–99.99%, while the staphylococci group was reduced to a lesser extent, but in the range 94.67–99.99%.²¹

In this context, the combination of access through endoscopically assisted paracrestal tunnelling and the application of diode laser for implant surface decontamination, with optional simultaneous regenerative therapy, could be further explored. However, it is important not to injure intact peri-implant soft tissues. The use of radial firing tips for lasers ensures the laser emits in a single direction, which can protect the peri-implant soft tissue and bone, particularly in the aesthetic region.²² The use of support immersion endoscopy techniques could aid in achieving better visualization and control, during and after implant surface decontamination protocols in peri-implantitis (Figure 1). In particular, immersion endoscopy can be performed in cavities that are not accessible to simple inspection, for example, within an alveolus or bony cavity. Immersion endoscopy permits close-up viewing at high magnification, as well as contact endoscopy.²³

Antimicrobial photodynamic therapy

This treatment modality uses a non-toxic photosensitizer agent that binds selectively to target cells. The photosensitizer has no effect until it is exposed to a low-intensity pulsed diode laser (wavelength 660 nm, power output of 11 mW) in the presence of oxygen, whereupon the excited photosensitizer reacts with the surrounding tissue molecules and generates reactive oxygen species that are selectively toxic to bacterial cells.²⁴ On absorbing a photon, the photosensitizer is promoted to a high-energy state, and transfers its energy to an oxygen molecule, resulting in the generation of free radicals, which could damage bacterial membranes and DNA.²⁵

Phenothiazinium dyes, such as toluidine blue O, methylene blue and azure dyes, bind poorly to human cells, and so have been widely employed to carry out photodynamic inactivation of Gram-positive and -negative bacteria and fungal cells, to which they bind more selectively. This reduces the collateral damage to human cells.²⁶

The fact that photodynamic inactivation is not species-specific is advantageous in that it is possible to kill all the bacteria present in a mixed infection. However selective photo-activated decontamination is also possible, through selecting a monoclonal antibody against a target organism, with which to conjugate the photosensitizer.²⁴ This approach represents an alternative to antibiotics and antiseptics for the treatment of localized infections, particularly for those caused by organisms that are resistant to conventional antimicrobial agents; moreover, it could be used on multiple occasions in the same treatment site or patient.²⁷

The anti-infective non-surgical therapy of peri-implantitis with photodynamic therapy (PDT) resulted in significant reduction of PPDs and BoP (P<0.05) for up to 12 months' follow-up.²⁸ Moreover, it was equally effective in the reduction of mucosal inflammation as with adjunctive delivery of minocycline microspheres (i.e. local drug delivery (LDD)). Thus, PDT was presented as an alternative approach to LDD. Importantly, current EFP S3 CPG suggest that there is insufficient evidence to make recommendations regarding the use of local antibiotics as adjuncts in the surgical treatment of peri-implantitis.¹ Furthermore, the treatment of peri-implantitis in a dog model using PDT resulted in a reduction in the microbiological load.²⁹ Similarly, a clinical study reported a significant reduction in A. actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia over contaminated implant surfaces in 15 patients after their treatment with PDT;³⁰ however, complete elimination of the three species was not achieved.

In summary, the advantages of PDT therapy over conventional antimicrobial agents are:

• Rapid killing of target organism;
• Limited resistance development;
• Antimicrobial effects can be confined to the site of the lesion; and
• The area of irradiation can be restricted using an optical fibre.

However, following current guidelines,¹ the use of PDT for implant surface decontamination is not recommended during surgical therapy of peri-implantitis.

Ultraviolet antimicrobial irradiation

Ultraviolet (UV) irradiation has been used in dental and medical settings for decontamination processes.³¹ The range of UV wavelengths found to be most effective were 220–300 nm, and the peak effectiveness was determined to be 256nm. The production of UV light employs an electrical discharge through low-pressure mercury vapour enclosed in a quartz glass tube. This technique produces a tube-type bulb with a primary wavelength of 253.7 nm, and is within the C spectrum of UV light (UVC). The UVC and UV germicidal irradiation (UVGI) forms of radiation have both been demonstrated to deactivate bacteria, fungi, viruses and mycoplasmas.³¹

UVGI affects the double-bond stability of adjacent carbon atoms in organic molecules including pyrimidines, purines and flavin. UV inactivation of micro-organisms results from the formation of dimers in RNA (uracil and cytosine) and DNA (thymine and cytosine). Among the applications of UVGI irradiation on indoor bio-contaminants is the control of the transmission of infectious diseases in medical facilities.^32,33 In fact, there is a growing trend for UVGI applications, for example in the food processing industry or for treatment of water. In one study, UV was used to reduce the concentration of airborne micro-organisms.³⁴

The germicidal effects of UVC irradiation on oral biofilms remain unclear, and its effectiveness on a peri-implantitis biofilm remains to be fully understood. UV irradiation of the implant surface prior to implantation has been reported to reduce the bacterial adhesion of Staphylococcus aureus and S. epidermis on the titanium surface.³⁵ The mechanisms underlying the ultraviolet functionalization of the titanium include increased hydrophilicity, removal of hydrocarbons, and electrostatic optimization,³⁶ and it has been reported that these might improve osseo-integration.³⁷

Conclusions

Both preclinical and clinical studies investigating the decontamination of implant surfaces have demonstrated that effective decontamination can be partially achieved through a combination of various cleaning protocols.

Electrolytic therapy has recently been explored as a treatment alternative to remove biofilms. However, these studies are still preliminary and further clinical trials are needed.

EFP S3 CPG do not recommend the routine use of systemic antibiotics as an adjunct to non-surgical or surgical treatment in patients with peri-implantitis.

The use of adjunctive local antimicrobial agents during the SPIC programme is not recommended to reduce the risk of recurrent peri-implantitis.

High-magnification microsurgical tools, such as endoscopy systems, could be perfected and used as an intra-operative control method during the decontamination of implant surfaces in order to verify effective decontamination.

Current guidelines advise that dental teams providing implant therapy be equipped with the professional expertise necessary for managing peri-implantitis. Owing to the complexity of the surgical treatment of peri-implantitis, it is recommended that such procedures be undertaken by dentists who have received specific training in this area, or by specialists.

An integrated and patient-centred management of peri-implantitis should be followed. This protocol may include:

• Preventive interventions (before/after implant placement);
• Non-surgical intervention;
• Early re-assessment (6–12 weeks);
• Surgical intervention if therapy endpoints (implant level residual PPD ≤5 mm, ≤1 point of BoP, and no suppuration) of peri-implantitis have not been achieved;
• Regular SPIC programme.