Regenerative Treatment of Peri-Implantitis Following Implant Surface Decontamination With Titanium Brush and Antimicrobial Photodynamic Therapy: A Case Series With Reentry

Peri-implantitis is a biofilm-induced inflammatory condition that affects both hard and soft tissues around osseointegrated dental implants.¹  Soft-tissue inflammation is clinically recognized by peri-implant bleeding on probing (pBOP) associated with increased peri-implant pocket probing depth (pPD), while progressive bone loss is identified on radiographs.²  Unfortunately, emerging evidence suggests that pBOP and pPD may be considered as poor indicators of ongoing peri-implant pathology with a considerable false-positive rate together with a risk of iatrogenic damage by probing of dental implants.^3,4  Therefore, data gathered from pBOP and pPD should be associated with the radiographic assessment of crestal bone levels to obtain an incontrovertible diagnosis. It has been claimed, however, that intraoral radiography lacks the accuracy for assessing interproximal bone defect morphology⁵  and often underestimates the intrasurgical bone loss at the correspondent site,⁶  since the intraoperatively measured peri-implant bone levels tend to be more apical than the radiographic bone levels.⁷  The suspected unreliability of intraoral radiographs in detecting the actual bone defect anatomy in the diagnostic phase can be transferred to the evaluation of peri-implant bone defect regeneration. Indeed, even more sophisticated radiologic examinations such as cone-beam computerized tomography, under certain conditions, may be inaccurate in assessing bone regeneration around augmented defects.⁸  This is mainly due to metal artifacts masking osseointegration, shallow bony defects, and other peri-implant radiolucencies that may impede a correct evaluation of the residual bone architecture.⁹ 

All of these findings taken together seem to indicate that reentry surgery rather than pPD and radiographs may allow clinicians to precisely evaluate the actual 3-dimensional bone gain obtained following regenerative treatment of peri-implantitis defects. Interestingly, despite the questionable predictive value of clinical and radiologic examinations in the assessment of the residual bone defect after regenerative procedures, only few in vivo studies^10–18  have shown irrefutable images of the augmented bone at the reentry phase in humans. When it comes to peri-implantitis treatment, the goal is to remove all debris attached to the implant surface triggering the chronic inflammatory process.²  These include biofilm alone, calculus, necrotic bone, or a combination of all of these elements. Several instruments have been proposed to decontaminate implant surfaces, including titanium brushes and antimicrobial photodynamic therapy (aPDT), with no clear evidence to support the superiority of a specific method over another.¹⁹  Emerging evidence suggests that most chemical and mechanical protocols alone are not effective in completely removing the biological debris, so that only a partial decontamination can be achieved.²⁰  Therefore, it may be speculated that an efficacious response to peri-implantitis treatment is one that combines chemical and mechanical therapies.

In view of the above, the aim of the present study was to report the reentry phase after regenerative surgical therapy of peri-implantitis following combined mechanical and laser-assisted decontamination to allow direct visualization of the actual bone gain and the residual bone defect at each treated implant.

The present prospective investigation included patients diagnosed with peri-implantitis treated with a regenerative approach. The diagnosis was established based on clinical and radiologic findings currently adopted in the diagnostic algorithm for peri-implant disease, namely, pBOP, pPD ≥6 mm, and radiographic evidence of bone loss ≥3 mm.¹  Furthermore, patients were enrolled if presenting with (1) no implant mobility, (2) presence of ≥2 mm of keratinized tissue, (3) treated chronic periodontitis and proper periodontal maintenance care, (4) no uncontrolled systemic diseases that may constitute contraindications to oral surgery procedures, (5) no concomitant therapies with antiresorptive agents including bisphosphonates and human monoclonal antibodies, and (6) nonsmoking or light smoking habits (<10 cigarettes per day). Patients were excluded if presenting clear indications of implant removal, such as nonretentive peri-implant bone defects associated with pPD >8 mm and a radiographic bone loss >50% of the implant length.²¹  Patients unwilling to undergo further surgical interventions, thus preferring removable prosthetic solutions, were also excluded.

All patients were treated in a private practice setting on an outpatient basis under local anesthesia in accordance with the Declaration of Helsinki on ethical principles for medical research involving human subjects. All surgical procedures were performed by the same surgeon. Each subject was provided a detailed description of the treatment plan and was required to sign an informed consent form.

All patients were treated according to a standardized protocol involving mechanical and chemical decontamination of the implant surface and bone augmentation procedures.¹⁸  In brief, paramarginal incisions were made to reflect mucoperiosteal flaps at the buccal and oral aspects. Granulation tissue was meticulously removed from the defect area, and the implant surface was debrided and instrumented using titanium curettes and rotary titanium brushes (Ti-Brush, Straumann, Basel, Switzerland) fixed on a surgical handpiece, oscillating in a clockwise/counterclockwise direction at low speed (800 rpm for 1 minute) under copious irrigation with sterile saline solution. Once the biofilm was macroscopically removed, aPDT was locally performed with a specific setup (HELBO, Bredent Medical, Senden, Germany). A solution of phenothiazine chloride dye consisting of methylenthioniniumchlorid (HELBO Blue Photosensitizer, Bredent Medical) was applied on the implant surface and surrounding tissues and left in place for 3 minutes. Subsequently, the surgical area was rinsed vigorously for 1 minute with sterile saline solution, and the photosensitizer was photo-activated at 6 sites per implant for 10 seconds each by means of a handheld 100-mW diode laser with a wavelength of 660 ± 10 nm (HELBO TheraLite Laser, Bredent Medical) equipped with a dedicated probe (HELBO 3D Pocket Probe, Bredent Medical) providing a power density of 60 mW/cm². Both the intrabony and the supracrestal components of the peri-implant defect were grafted with autogenous bone chips harvested from the neighboring area mixed with deproteinized bovine bone mineral (DBBM) particles (Bio-Oss, Geistlich, Wolhusen, Switzerland) in a 70:30 ratio. The graft was stabilized with a 0.2-mm-thick titanium mesh (KLS Martin, Tuttlingen, Germany) trimmed and adapted to the surgical defect to create a proper bone contour. A resorbable collagen membrane (Biogide, Geistlich) was finally applied over the titanium mesh. Periosteal horizontal releasing incisions were performed to mobilize the flaps and obtain a tension-free first-intention closure. The patient was instructed to rinse 3 times daily with 0.2% chlorhexidine mouthwash rinse solution for 1 minute starting 1 week prior surgery until 2 postoperative weeks. The antibiotic therapy consisted of 1 g amoxicillin clavulanate starting the day before the surgery twice daily for 6 days. Anti-inflammatory and analgesic therapy was prescribed (ibuprofen 600 mg, 3 times daily) during the first 2 days and according to the patients' individual needs thereafter.

After a submerged healing period ranging from 6 to 9 months, the reentry surgery was performed to remove the titanium mesh and reconnect the abutment and the prosthesis.

In all sites, the clinical evaluations were performed by the second operator, who was blinded with respect to the study outcome. During the initial regenerative procedure (T₀) after flap elevation, each peri-implantitis lesion was classified according to the bone defect configuration as proposed by Schwarz and coworkers.²²  The overall vertical defect (oVD), defined as the distance from the top of the implant platform to the bottom of the bone defect, was measured at the level of the deepest aspect. The oVD was further divided into a supracrestal (sVD) and an intrabony (iVD) component. The sVD was measured as the linear distance from the alveolar bone crest to the implant platform, while the iVD was measured as the distance from the alveolar bone crest to the bottom of the defect. The measurements were performed with a periodontal probe (PCP-UNC 15, Hu-Friedy, Chicago, Ill) and rounded at the nearest half millimeter. The same measurements were registered at the reentry surgery (T₁) to calculate the overall vertical bone gain (oVBG) divided into a supracrestal (sVBG) and an intrabony (iVBG) bone augmentation with related percentages of defect resolution (DR) and residual defect classification. Data at the implant level were reported as mean values ± standard deviations using a commercially available statistical software (IBM SPSS Statistics 24.0, IBM Corp, Armonk, NY).

A total of 6 adult patients (4 women, 2 men; mean age: 60.83 ± 4.09 years) diagnosed with peri-implantitis were included. Overall, 11 osseointegrated dental implants supporting single crowns or bridgework restorations were consecutively treated. The baseline demographic data and defect characteristics are presented in Table 1. For each case, the initial defect at T₀ and residual defect at T₁ are illustrated in Figures 1 through 6. Healing proceeded uneventfully in all patients. At the reentry surgery, no evidence of granulation tissue, purulence, or progressive bone resorption was found. Newly formed bonelike tissue hardly distinguishable from the existing bone was found in intimate contact with the implant surface at most of the implant sites. A modest amount of augmented bone was obtained at only 1 mandibular site, resulting in persistent dehiscence-type defects associated with a supracrestal component. The most frequently observed configurations of bone defects were Class Ic and Class Ie. Most bone defects were associated with a supracrestal component. The measurements recorded at T₁ are reported in Table 2. The mean oVD decreased from 4.22 ± 1.05 mm at T₀ to 1.13 ± 1.38 at T₁. This resulted in a mean oVBG of 3.09 ± 1.16 mm, which corresponded to a calculated overall mean DR score of 76.02% ± 25.5%. The mean sVD decreased from 2.93 ± 1.4 at T₀ to 1.78 ± 1.35 at T₁. The resultant mean sVBG was 1.37 ± 0.99 mm, corresponding to a calculated overall mean DR score of 50.82% ± 32.69%. With respect to the mean iVD, a decrease from 2.55 ± 1.01 mm to 0 mm was observed from T₀ to T₁, resulting in a mean DR score of 100%. At the reentry surgery, in all except 3 implants, at least 1 bone wall was present in intimate contact with the implant and reaching the top of the implant platform. Conversely, in 2 mandibular sites, supracrestal defects of different magnitude were still observed.

A combined mechanical and chemical decontamination of contaminated implant surfaces together with regenerative procedures and submerged healing yielded promising results in terms of clinical healing and new bone formation. This was confirmed at the reentry surgery, which allowed direct visualization and quantitative measurement of the bone gain around each implant. The visual assessment of the regenerated peri-implantitis defect is crucial, as conventional clinical indices together with radiological examinations may not be considered completely trustworthy in the evaluation of the regenerative treatment outcome.

The use of a titanium brush aimed to disrupt the bacterial biofilm on the implant surface. The treated surface examined after the mechanical decontamination appeared smooth and clean, with no macroscopic evidence of persistent biofilm, a feature already reported by An and coworkers.¹¹  It is worth noting that titanium brushes are capable of effectively instrumenting the thread and valley areas, which may be considered as the most difficult-to-access regions of a contaminated implant.²³  This may explain the positive outcome achieved in the present study, highlighting the increased benefits in the additional use of titanium brushes during regenerative treatment of peri-implantitis.²⁴  It must be noted, however, that the effectiveness of the mechanical treatment has been verified visually with magnifying devices. The undercuts of the threads and the adhesion of biofilm in the porosity of microstructured roughened surfaces may render the mechanical treatment still unpredictable. The adjunctive use of chemical decontamination methods should be contemplated to remove any residual biofilm remnants and destroy the organic components of bacteria still attached to the implant surface. In peri-implantitis lesions, a heterogeneous mixed infection can be detected, with a certain prevalence of Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Porphyromonas gingivalis, and Tannerella forsythia.²⁵  It is noteworthy that both gram-positive and gram-negative bacteria have an overall negatively charged cell surface, which acts as an electroattractive scaffold for cationic photosensitizers.²⁶  Thus, the use of cationic phenothiazinium derivatives such as the phenothiazine chloride dye used in the present study may be extremely useful at peri-implantitis lesions because of their high binding affinity for both gram-positive and gram-negative bacteria. In this respect, the photosensitizer is able to access this multispecies biofilm at the most restricted regions of the implant microstructure, including the valley area and the micropores of rough surfaces. In addition, systemic toxicity is largely absent outside the irradiated zone, and no antimicrobial resistance is developed against the dye. All of these advantages taken together support the use of aPDT as an adjunctive treatment modality in case of peri-implant disease. The outcomes achieved in the present study fully agree with the results observed in a recent case series reporting improved crestal bone level changes following aPDT associated with regenerative therapy of peri-implantitis defects.²⁷  The authors reported a mean bone gain of 3.78 mm, which is similar to that obtained in the present study. Similarly, Schwarz and colleagues¹⁶  found a mean defect augmentation of 3.5 mm corresponding to a calculated mean DR of 85% considering implants that healed uneventfully. The results reported herein favorably comply with those showed by Schlee and coworkers,¹⁴  who measured mean bone gain values ranging from 2 to 4 mm depending on defect morphology. Higher values of mean bone gain have been observed at reentry following regenerative therapy of peri-implantitis. Froum and Rosen¹³  found a mean bone fill of roughly 5 mm, ranging from 2 to 9 mm. However, it is worth mentioning that initial defect depths varied from 3 to 12 mm. In the present study, the fact that the oVD ranged from 2 to 6 mm may explain this discrepancy. Nevertheless, the mean percentage of bone fill was similar to that reported in the present study, namely, 73% and 76%, respectively. Accordingly, Parma-Benfenati and coworkers¹⁵  reported a mean bone gain of almost 5 mm, with a mean pretreatment defect depth of approximately 5.5 mm at baseline, resulting in a mean bone fill of 91%. Interestingly, all implants that healed with a submerged approach and achieved complete defect fill had a machined surface. Conversely, the implants treated in the present study were characterized by rough surfaces. Thus, one may speculate that surface topography might play an important role in the prognosis of the treatment. In this regard, it should be noted that both titanium brushes and aPDT have a modest impact on implant surface modifications. A recent in vitro micro-topographical analysis showed that titanium brushes did not reveal significant changes in roughness parameters or surface chemical composition in sandblasted and acid-etched titanium disks as compared with untreated samples.²⁸  Similarly, Park and coworkers²⁹  did not observe any differences in surface roughness values after instrumenting sandblasted and acid-etched titanium disks with a commercially available titanium brush. At the same time, implants with sandblasted and acid-etched surfaces treated with aPDT did not show microscopical alterations such as melting, glossiness, cracking, ripple pattern, and slip-line formation following decontamination.³⁰  In the present study, at each site, the existing prosthesis was removed to perform tension-free flap release and ensure undisturbed healing. This crucial aspect has been confirmed by Wen and coworkers,¹⁷  who stated that it is pivotal to achieve primary wound closure to ensure a successful and predictable outcome following regenerative therapy of peri-implantitis. The authors adopted a comparable approach to that reported in the present study, namely, debridement of inflamed granulomatous tissues, implant surface decontamination, grafting of the intrabony component with autogenous bone and DBBM, graft stabilization with nonresorbable membrane, and primary closure. An average bone gain of 96% was obtained, which is comparable with the mean bone fill of 100% achieved in the present study considering the intrabony defect component. This finding clearly points out that defects that are outside of the bony housing and defects beyond the line drawn between 2 adjacent bone contours may not be suitable for this approach. Indeed, in the present study, an overall mean DR score of 50% was observed for the supracrestal component, meaning that the regeneration of suprabony defects was not predictable. Thus, it might be suggested to manage supracrestal defects featured by consistent horizontal bone loss with implantoplasty procedures of exposed threads.³¹  This could be particularly true in the posterior mandible, where supracrestal defects were not completely resolved in the present study. Apart from the reduced surgical access in the said region, unsatisfactory bone augmentation can be related to the native alveolar bone anatomy. The bone architecture is generally characterized by thick compact cortical bone and low blood supply with a consequent negative effect on bone regeneration in this region.³²  In addition, the flat morphology of the residual ridge did not allow proper containment of the bone graft along with the clot, further jeopardizing the regenerative outcomes. Because these factors apply to normal conditions, it is safe to assume that in compromised circumstances such as the regenerative treatment of infected implants, the posterior mandible is one of the most challenging anatomical sites to approach.

The data obtained in the present study might be useful for calculating an adequate sample size in future clinical trials aimed to evaluate the effectiveness of these methods used alone and combined. In this respect, it must be noted that the results reported herein should be interpreted cautiously, because the single effect of each technique or a possible synergism cannot be extrapolated from the present case series.

Regenerative treatment of peri-implantitis following meticulous implant surface decontamination with titanium brush and aPDT showed promising results. The regenerative potential was strictly related to the defect morphology. Further confounding factors could not be identified because of the limited sample.

Abbreviations

aPDT

antimicrobial photodynamic therapy

DBBM

deproteinized bovine bone mineral

DR

defect resolution

iVBG

intrabony vertical bone gain

iVD

intrabony vertical defect component

oVBG

overall vertical bone gain

oVD

overall vertical defect

pBOP

peri-implant bleeding on probing

pPD

peri-implant pocket probing depth

sVBG

supracrestal vertical bone gain

sVD

supracrestal vertical defect component

The authors whose names are listed in the present submission certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements) or nonfinancial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this article. This clinical report did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.