Keywords guided tissue regeneration - periodontics - oral surgery - peri-implantitis
Introduction 
            The insertion of dental implants in clinical practice necessarily involves facing,
               statistically, a variable number of cases of mucositis and peri-implantitis.
            Mucositis is a reversible inflammatory process, limited to the peri-implant soft tissue,
               without affecting the attachment epithelium or the bone tissue.[1 ]
               
            Peri-implantitis, on the other hand, is an inflammatory process which, in addition
               to affecting the soft tissues, is associated with peri-implant bone loss.[2 ] Both pathological manifestations have a bacterial etiology, that is, they are caused
               by biofilms that colonize the surfaces of the implant fixture and the abutment.[3 ]
               [4 ]
               
            Several studies have evaluated the incidence of peri-implantitis. According to Derks
               et al,[5 ] 45% of patients with implants are affected by peri-implantitis. In contrast, Atieh
               et al[6 ] and Rakic et al[7 ] obtained results in agreement with percentages of 18.8 and 18.5%, respectively.
               On the percentage differences reported by these studies, it is necessary to clarify
               that the authors evaluated different threshold values in the definition of pathology.
               To standardize the concept of peri-implantitis, in the 2017 World Workshop on the
               Classification of Periodontal and Peri-Implant Diseases and Conditions, a higher probing
               than baseline associated with clinical signs of inflammation was reported as a pathological
               clinical sign.[8 ] Peri-implantitis is an inflammatory process which affects the tissues around the
               osseointegrated implant leading to a loss of the supporting bone tissue. The cause
               is either infectious or it is an incorrect implant-prosthetic passivation (occlusal
               trauma), although both causes can be found clinically. The radiographic examination
               allows to easily distinguish an occlusal trauma peri-implantitis from a bacterial
               one.
            To safeguard the osseointegration process, therapies are used that include the use
               of antibiotic and anti-inflammatory drugs, as well as a possible revision of surgical
               curettage of the affected area, and also guided bone regeneration (GBR). All therapies
               aim to eliminate bacteria from the surface of the implant both in the covered (without
               affecting the gum) and in the open (incising the gum and lifting it). When inflammation
               is present, therefore, it is considered necessary to use methods to decontaminate
               implant surfaces, with the goal of prolonging the prognosis of rehabilitations. In
               fact, the complete replacement of affected implants is not indicated, both in terms
               of morbidity and costs. Instead, we should aim at the development of predictable methods
               to restore implant health.
            Several methods of implant decontamination have been suggested, including mechanical
               therapies aimed at removing bacterial biofilm and smoothing the involved implant surfaces
               and chemical therapies such as application of antiseptics and local and systemic antibiotics.
               However, there is no consensus on the most effective protocol for detoxification of
               implant surfaces.
            Mechanical removal of bacterial aggregates on the surfaces, using powder spray with
               erythritol particles, accelerated by air pressure, is a method that is positively
               reported in the literature with regard to clinical improvements in depth and bleeding
               on probing.[9 ]
               
            It has also been demonstrated that local antimicrobial agents play an important role
               in peri-implant bacterial control, particularly doxycycline, a bacteriostatic molecule
               belonging to the tetracycline class which is inserted into the peri-implant pocket
               and can be effective for up to 14 days.[10 ]
               
            Another critical site that easily colonized by bacteria and difficult to reach for
               decontamination is the fixture-abutment interface, in this regard do Nascimento et
               al[11 ] demonstrated how the application of iodoform paste in the fixture-abutment connection
               has a decisive role in preventing bacterial colonization.
            However, the exclusively nonsurgical approach was inadequate for the treatment of
               moderate-to-severe peri-implantitis where a surgical approach is instead required
               to reach the deepest implant surfaces to be decontaminated to restore the anatomy,
               to eliminate the peri-implant pockets, and to perform a regeneration of the present
               bone defect.
            It has been shown that vertical peri-implant bone defects can and should be treated
               by regenerative surgery, using only autologous or heterologous bone in combination
               or not with a membrane (GBR) and growth factors.[12 ]
               
            Studies have evaluated that platelet concentrates, obtained by centrifugal separation
               of venous blood which include growth factors, are involved in increased angiogenesis
               activity, stimulate fibroblast and osteoblast activity, and increase hard and soft
               tissue regeneration.[13 ] A study conducted by Schlee et al investigated the efficacy of using electrolytic
               decontamination using GalvoSurge (GS1000, GalvoSurge Dental AG, Widnau, Switzerland)
               in association with spray treatment of implant surfaces and without spray treatment
               of implant surfaces.[14 ]
               
            The aim of this study is to present the management of a dental implant clinical case
               in the esthetic zone (left maxillary central incisor; 2.1) affected by peri-implantitis,
               with a combination of both chemical and surgical techniques to restore implant health.
         Case Report 
            This case report describes a clinical case of a patient, 62-year-old male, Caucasian,
               in good general health, without any systemic problems, nonsmoker, and not on medication
               (ASA1: a normal healthy patient. Example: Fit, nonobese [BMI under 30], a nonsmoking
               patient with good exercise tolerance).
            The patient has an implant (Bredent, Senden, Germany) in zone 2.1 placed with a postextraction
               technique with immediate loading in 2014.
            The patient reported that he underwent 6-month maintenance therapy and, in fact, from
               the compilation of the periodontal chart and radiographic evaluation (full endoral),
               a good periodontal health is described with only one >5-mm probing in the mesiopalatal
               site of tooth element (left maxillary first molar 2.6), corresponding to a prosthetic
               restoration and with slight plaque accumulation. A good oral hygiene status is noted
               given the absence of bleeding at the probing and a plaque index of 5%. In correspondence
               of the implant in zone 2.1, on the other hand, pathological probes were found, especially
               in the central vestibular site with PD = 9 mm ([Fig. 1 ]).
            
                  Fig. 1  Periodontal chart at baseline. 
            Periapical X-ray showed peri-implant bone resorption and cone-beam computed tomography
               (CBCT) showed a 5.5-mm circumferential deficit ([Fig. 2 ]).
            
                  Fig. 2  Clinical and radiographic image (2D, 3D) at baseline. 2D, two-dimensional; 3D, three-dimensional. 
            Clinically, the texture of the peri-implant mucosa is edematous, violet colored, but
               without loss of substance and/or exposure of the implant coils. Occlusal vision shows
               a clear deficit of mucogingival volume and/or bone in the vestibular side of the 2.1
               area ([Fig. 2 ]).
            We proceed with the treatment starting with a professional oral hygiene session, with
               decontamination of the implant area with erythritol Aereosol through a dedicated disposable
               tip inserted in the peri-implant defect itself (AIR-FLOW Master Piezon; EMS, Nyon,
               Switzerland).
            Subsequently, PERIOSTAT gel (iclated doxycycline) is applied, via a carrier with a
               tip, within the defect[10 ] ([Fig. 3 ]).
            
                  Fig. 3  (A, B ) application of antibiotic gel. 
            After 1 week from decontamination, the crown on implant 2.1 is removed, the cap screw
               is inserted with application of iodoform paste[11 ] and then a maryland bridge has been placed ([Fig. 4 ]).
            
                  Fig. 4  Insertion of the cap screw with iodoformic paste. 
            Once the soft tissues have healed, after 4 weeks, we can proceed with a regenerative
               surgery to regenerate the portion of peri-implant bone tissue lost due to peri-implantitis
               ([Fig. 5 ]).
            
                  Fig. 5  Surgical exposure of the peri-implant site. 
            Once anesthesia with vasoconstrictor (1:100,000) is performed, a flap is incised according
               to Canullo et al.[12 ]
               
            Vestibularly, the design of the flap is similar to a flap for the treatment of multiple
               recessions in mucogingival surgery therefore it involves the following:
            
               
               
                  
                  A crestal incision.
                   
               
               
                  
                  Incisions to draw surgical papillae bilaterally up to three teeth distal from the
                     area to be regenerated.
                   
               
               
                  
                  Flap dissection at half thickness up to the amelocemental junction and at a full thickness
                     apically to it.
                   
               
               
                  
                  Deepithelialization of the anatomic papillae to create a connective receiving bed
                     for the surgical papillae.
                   
               
               
                  
                  The lateral extension of the incisions allows to have a passivation of the flap without
                     the need of vertical unloading cuts.
                   
                
            Once the flap has been removed, the defect degranulated and washed with rifampicin
               (RIFADIN, Sanofi, Milan, Italy), the implant is decontaminated using an electrolytic
               approach using GS1000 GalvoSurge Dental AG[14 ] ([Fig. 6 ]).
            
                  Fig. 6  Decontamination using GS1000 GalvoSurge Dental AG. 
            Once the electrolytic decontamination is completed, the bone defect is filled with
               a deproteinized bone graft (Bioss, Geistlich Pharma AG, Wolhusen, Switzerland) mixed
               with autologous bone harvested intraorally and then covered with a resorbable membrane
               (Cytoplast Ti-250, Deore Materials, Osteohealth, New York, United States; [Fig. 7 ]).
            
                  Fig. 7  Defect filling. 
            The membrane is then fixed with two metal mini-screws and platelet aggregates are
               inserted to promote healing[13 ] ([Fig. 8 ]).
            
                  Fig. 8  Membrane fixation with two mini screws and insertion of platelet aggregates. 
            Once the regenerative phase is completed, the flap is further passivated through periosteal
               incisions apical to the flap and then sutured to the anatomic papillae.
            Sutures: PTFE 5.0 (Omnia, Fidenza, Italy; mattress suture on the implant area) and
               PGCL 6.0 (Monofast, Kirkinil, Greece; detached stitches and sling stitches on the
               papillae; [Fig. 9 ]).
            
                  Fig. 9  Sutures. 
            The patient is instructed in postsurgical oral hygiene maneuvers as follows:
            
               
               
                  
                  Avoid brushing the area of surgery until suture removal (14 days).
                   
               
               
                  
                  To rinse after the first 24 hours with CHX mouthwash (Curasept, Saronno, Italy) at
                     0.12% during the same period of time twice a day.
                   
                
            Prescribed: amoxicillin of 875 mg + 125 mg Ac. Clavulanic for 4 days 2 times a day
               and nonsteroidal anti-inflammatory drugs (NSAIDs) as needed.
            The patient is checked every 7 days during the first month and then monthly for 12
               months, when a new CBCT is then performed ([Fig. 10 ]).
            
                  Fig.10  Clinical and radiographic (2D, 3D) follow up at 1 year. 2D, two-dimensional; 3D,
                  three-dimensional. 
            Results 
            During the numerous controls performed in the first 12 months after surgery, no clinical
               problems were detected, with an excellent control by the patient of home hygiene and
               a stability of periodontal indices, completely within the physiological range.
            There is a gingival recession, especially on the distal side in relation to the lack
               of bone peak on the lateral incisor. At 12 months, both an endoral periapical control
               X-ray and a CBCT were performed, showing a complete circumferential filling of the
               treated peri-implant defect. In fact, a total bone coverage of the shoulder of the
               2.1 implant can be seen, with a bone gain of 6 mm on the mesial aspect and 5 mm on
               the distal aspect.
         Discussion 
            The treatment of peri-implant lesions has long been a controversial topic. The purpose
               of the present case-report was to define a new surgical and regenerative protocol
               to restore peri-implant tissue health and esthetics in the esthetic zone. The results
               of the follow-up of more than 2 years showed an excellent reosteointegration of the
               bone around the implant affected by a combined defect similar to a crater in the most
               apical part and a vertical defect in the distal region.
            It is important to emphasize that the result obtained from the clinical case is the
               sum of a series of biological and mechanical factors that a clinician should consider.
               First of all, a nonsurgical and antibiotic approach was used to treat the periodontal
               pocket that presented bleeding and suppuration phenomena. The aim of this first approach
               is also to make the tissues less edematous and more manageable from a surgical point
               of view.[10 ]
               
            Microbiological studies conducted by Canullo et al[3 ] have shown that the implant connection, being an oxygen-poor site, tends to select
               anaerobic gram-negative bacteria. This, during the life of the implant, especially
               in less stable connections or incongruous prosthetic restorations, leads to a micropumping
               phenomenon that results in an increased risk of peri-implantitis. For this reason,
               4 weeks before performing the regenerative surgical therapy, it was necessary to perform
               a removal of the previous prosthetic artifact and at the same time, iodoform paste
               was inserted together with a new cap screw.[11 ]
               
            It is important to underline that the removal of the crown allows from a clinical
               point of view a better access to the pocket and to the surface to be decontaminated.
            When approaching a vertical regenerative case, one of the most complex aspects is
               certainly the management of the flap. For this reason, in this case, a platelet concentrate
               has been wrapped around the screw cap with the aim to enhance the healing of soft
               tissues. In addition, some studies in the literature have drawn attention to the fact
               that the presence of leukocytes in platelet concentrates may allow a greater control
               of postoperative infections and may be a protective factor in cases at risk of osteomyelitis.[15 ]
               [16 ]
               
            The surgical therapy used is initially characterized by the use of a coronally advanced
               flap for the treatment of multiple recessions. This allows for the avoidance of scarring
               in areas where release cuts might be necessary and ensures a greater blood supply
               to the flap.
            Total decontamination of the surfaces is required before regenerative surgery is performed.
               The presence of nano- and microparticles, bacterial-derived antigens, or ions on implant
               surfaces can lead to bone resorption or failure of osseointegration. To fully understand
               these biochemical mechanisms, osteoimmunology, a rapidly developing branch that studies
               the interrelationship between bone tissue cells and the immune system, has been introduced.[17 ]
               
            Indeed, initially the inflammatory infiltrate together with macrophages allows for
               a proregenerative peri-implant environment. Subsequently, if the inflammation is not
               resolved or reactivated due to the immunogenic signals of the contaminants, infections
               with subsequent bone loss or aseptic inflammation could occur.[17 ]
               
            Nonsurgical methods of surface decontamination have demonstrated suboptimal results.[18 ]
               
            Methods of implant surface decontamination using mechanical, sonic, and ultrasonic
               scalers, laser, air flow, and various chemical solutions, such as chlorhexidine digluconate,
               citric acid, and hydrogen peroxide, have been proposed in many studies.[19 ]
               [20 ]
               [21 ] In addition, interesting results have been obtained with the use of plasma argon.[22 ]
               
            However, in the literature, results about newly formed bone vary widely, and it is
               often difficult to quantify how much of the radiographically present bone is actually
               osseointegrated on the implant surfaces.
            Small areas of osteitis around the body of implants in peri-implantitis may remain
               contaminated despite mechanical removal of granulation tissue, so it may be useful
               to treat contaminated bone by topical application of rifampicin.
            Once the granulation tissue around the implant was removed and the recipient bone
               site was exposed, a new tool called GalvoSurge was introduced to decontaminate the
               surface. The recently developed system involves using an electric current on an implant
               treated with sodium formicate. Hydrogen anion (OH − ) and cation (H+ ) are dissociated by the current. The highly reactive H+  ions form hydrogen bubbles on interaction with the stray electrons which lift the
               biofilm from the implant surface.[13 ] An in vitro  study demonstrated complete sterilization of surfaces after electrolytic treatment.[23 ]
               
            An extremely interesting aspect is represented by the possibility to decontaminate
               an implant surface without changing its surface microtopography and therefore without
               affecting its physical properties.
            Promising reosteointegration of contaminated implant surfaces after electrolytic cleaning
               has been demonstrated in two clinical studies.[17 ]
               [24 ]
               [25 ]
               [26 ]
               [27 ]
               
         Limitations 
            The limitations of this technique are represented by the impossibility to regenerate
               defects above the bone peaks, so a combined regenerative and resective approach should
               not be underestimated in cases that require it. The use of GalvoSurge in fact would
               allow the removal of particular matter resulting from the release of titanium particles
               around the surface without affecting the healing process. In the literature, there
               is much debate about the influence of metal particles on tissues. In fact, this same
               particulate could result in a negative modulation of osteoimmunology and could result
               in an aseptic foreign body reaction around the implant.
            Ultimately, it can be said that electrolytic cleaning, although recently introduced,
               is an extremely interesting method for the regenerative management of peri-implants.
               Future studies will be needed to understand the dynamics around healing of sites treated
               with GalvoSurge.
            Nonmechanical therapies involve the use of antiseptic and antibiotic solutions, both
               in the form of washes and in slow-release forms from the gel to the impregnated fibers.
               The laser can sterilize surfaces. The common limitation of all therapies that are
               limited to eliminating bacteria by disinfecting or sterilizing is that they will recolonize
               the spaces as bacteria are not found only on implants. It becomes essential to correct
               these bone defects, so that they do not return to being reservoirs of infection. GBR
               is useful in this sense, unless you resort to resective therapies that will bring
               decontaminated surface outdoors into cleanable areas. It must be observed, however,
               how important it is to intercept, together with the microbiological contamination,
               the possible iatrogenic background of the peri-implant disease. Failing in classifying
               the possible surgical or prosthetic triggering factors may lead to a failure in the
               treatment outcomes.[28 ]
               [29 ]
               [30 ]
               [31 ]
               [32 ]
               [33 ]
               [34 ]
               [35 ]
               [36 ]
               [37 ]
               [38 ]
               [39 ]
               [40 ]
               [41 ]
               [42 ]
               
         Conclusion 
            The presented case demonstrated a new and promising protocol for the regenerative
               management of sites affected by peri-implantitis. The ability to regenerate healthy,
               viable bone around implants is critical in cases where esthetic demands are more demanding.
               Combining these surgical techniques and these pharmacological protocols will allow
               clinicians to offer safer and more predictable rehabilitations over time. Future studies
               will be necessary to fully understand the timing and dynamics regarding wound healing
               of sites treated with GalvoSurge. In addition, a comparison of the healing dynamics
               of treated sites in relation to different implant surfaces would be desirable.