The Effect of Adjunctive Therapies in Regenerative Treatment of Stage III Grade C Periodontitis
Condition: Periodontitis; Lasers; Ozone; Wound Healing; Regeneration
MeSH terms: Periodontitis
Study type: Interventional

Summary: 
      Anti-infective procedures play a very important role in the success of regenerative surgical
      treatment of aggressive periodontitis, Grade C periodontitis, which shows the newly named
      molar-incisor pattern according to the 2017 World Workshop Classification of Periodontal
      Diseases. In the present study, it was aimed to analyze the effects of photodynamic,
      photobiomodulation, and ozone therapy applications on periodontal healing, both clinically
      and immunologically, in addition to the surgical regenerative treatment of aggressive
      periodontitis. Forty adult individuals diagnosed with aggressive periodontitis who applied to
      Gazi University Faculty of Dentistry Department of Periodontology for the treatment of
      periodontal disease were included in the study. In addition to the regenerative surgical
      treatment using cortico-cancellous particle allograft and a resorbable collagen membrane in
      randomly determined areas with multiple intraosseous defects, topical ozone, antimicrobial
      photodynamic, and light-emitting diode (LED) photobiomodulation treatments were applied.
      Periodontal clinical parameters [plaque index (PI), gingival index (GI), bleeding on probing
      (BOP), probing pocket depths (PPD), clinical attachment level (CAL), gingival recession (GR),
      and width of keratinized gingival (WKG)] were examined and patient-centered postoperative
      evaluations, and early wound healing index (EHI) assessments were performed for 2 weeks after
      the operation. In addition, gingival crevicular fluid (GCF) samples from patients to
      determine the total amount and concentration of vascular endothelial growth factor (VEGF),
      interleukin -6 (IL-6), Runt-related transcription factor 2 (RunX2), NEL-like 1 (Nell-1),
      Osterix and samples were quantified by Quantitative Real-Time PCR. The repeated measures
      ANOVA model was used for the analysis of variables in which both group and time measurements
      were taken.
    

Detailed description: 
      Periodontitis is a chronic multifactorial inflammatory disease driven by the dysbiotic
      relationship between the host immune-inflammatory response and the commensal oral microbiota
      in plaque biofilms that results in the progressive destruction of the tooth-supporting
      apparatus (Papapanou et al., 2018). Several modifiable and non-modifiable factors including
      genetic, environmental, and systemic factors can influence its pathogenicity and alter
      patient's susceptibility to the development and severity of the periodontal disease (Kinane
      et al., 2017).

      According to the 2017 World Workshop classification, stages III or IV, grade C periodontitis,
      formerly defined as aggressive periodontitis, is characterized by the rapid progression of a
      particularly severe form of periodontal disease (Papapanou et al., 2018). According to the
      EFP S3 Clinical Treatment Guidelines, in patients with deep periodontal pockets (≥ 6 mm) step
      2 of periodontal therapy (subgingival instrumentation, with or without adjunctive therapies)
      may be insufficient, and step 3 of surgical periodontal therapy incorporated with
      regenerative procedures may be required to eliminate deep residual pockets and reconstruct
      the intrabony part of the defects, as well as prevent tooth loss (Sanz et al., 2020). Despite
      of some limitations of access flap periodontal surgeries such as increased risk of gingival
      recession, increased postoperative dentin hypersensitivity, and morbidity, regenerative
      surgical procedures have been shown to be efficacious for the treatment of intrabony defects
      in patients with severe periodontitis, with the rapid rate of progression (Diaz-Faes et al.,
      2020). To improve the outcomes of therapy in severe periodontitis patients, adjunctive
      interventions such as local or systemic antibiotics, and antimicrobial photodynamic or
      photobiomodulation therapies using lasers or light-emitting-diodes (LED) have been explored
      in non-surgical and surgical treatment approaches (Collins et al., 2022; Andere et al., 2022;
      Giannelli et al., 2018).

      Within the visible red or near-infrared (NIR) range of the spectrum (600 to 700 nm and 780 to
      1100 nm), low-level lasers (LLL) or LEDs have been widely utilized as an adjunct therapy for
      periodontitis treatment based on their photobiomodulation and decontamination effects, which
      primarily occur at the level of the cellular respiratory chain (Zhao et al., 2021). These
      modalities promote mitochondrial activity and activate the mechanisms, i.e., inducing
      intracellular metabolic changes, enhancing the cellular resuscitation system, increasing
      adenosine triphosphate (ATP) and extracellular matrix (ECM) production (Heidari et al.,
      2018). Through the biological characteristics of these approaches, various studies have shown
      to increase angiogenesis, promote modulation of the immunoinflammatory response, stimulate
      the processes of regeneration and epithelialization, and reduce postoperative symptoms. The
      use of LLLs or LEDs in conjunction with photosensitizing agents (optical absorption-dye) has
      been referred as antimicrobial photodynamic therapy (aPDT). This procedure stimulates the dye
      to form free radicals of singlet oxygen that will act as toxic to the target cells or
      bacteria mainly as a result of deterioration to the cytoplasmic membrane and DNA, thereby
      demonstrating anti-microbial activity at periodontal pathogenic bacteria in combination with
      periodontal treatment (Katsikanis et al., 2020). Similar to the biostimulatory features of
      LLLs or LEDs, adjunctive gaseous ozone therapy applications have been recently exploited
      because of their analgesic, immunomodulatory, and anti-inflammatory effects, which may have
      the ability to provide significant added benefits in both step 2 and 3 of the periodontal
      therapy due to its analgesic, immunomodulatory, and anti-inflammatory effects (Rapone et al.,
      2022). All these adjunct therapies have also been shown to have a positive effect on the
      proliferation and osteogenic differentiation of undifferentiated periodontal tissue cells or
      the direct stimulation of osteoblasts in several studies. However, little information exists
      regarding the efficacy of these modalities adjunct to the periodontal regenerative therapies
      on the processes and sequences of the healing and consequently, in the postoperative
      expression levels of biomarkers of inflammation, angiogenesis, and osteogenesis. Therefore,
      the objectives of the present study were: (i) to investigate the additional influence of
      multiple sessions of aPDT, LED photobiomodulation, and topical gaseous ozone therapy
      applications associated with surgical regenerative treatments by using an allogenic bone
      graft in combination with a collagen membrane on clinical and patient-centered outcomes in
      patients with stage III, grade C periodontitis, and (ii) to analyze mRNA expression levels of
      vascular endothelial growth factor (VEGF), interleukin -6 (IL-6), runt-related transcription
      factor 2 (RunX2), NEL-like 1 (Nell-1), and osterix in gingival crevicular (GCF) samples at
      baseline and the 1-, 3- and 6-month follow-ups after the treatment procedures.
    

Intervention name(s): Control group; Antimicrobial photodynamic therapy (aPDT) group; LED photobiomodulation group; Topical ozone group
Intervention type(s): Device; Device; Device; Device
Intervention description(s): Following local anesthesia, a full-thickness (muco-periosteal) access flap was elevated, granulation tissue was removed and direct instrumentation of the affected root surfaces was performed under the saline irrigation. Intrabony defects were filled with granules of allograft bone material and covered with a native porcine pericardial collagen membrane. The flaps were repositioned and sutured without any tension in order to achieve primary closure of the inter-dental area using a 5-0 mono-filament non-resorbable PTEF suturing material. On the 1st, 3rd, and 7th postoperative days, the sites in the control group received only saline irrigation for 1 min.; Following local anesthesia, a full-thickness (muco-periosteal) access flap was elevated, granulation tissue was removed and direct instrumentation of the affected root surfaces was performed under the saline irrigation. Intrabony defects were filled with granules of allograft bone material and covered with a native porcine pericardial collagen membrane. The flaps were repositioned and sutured without any tension in order to achieve primary closure of the inter-dental area using a 5-0 mono-filament non-resorbable PTEF suturing material. On the 1st, 3rd, and 7th postoperative days, aPDT group received additional application of a diode laser with a wavelength of 810 nm and a power rating of 200 mW (continuous mode). Indocyanine-green (ICG) as a photosensitizer at a concentration of 1 mg/ml was applied at the surgical site on both the buccal and the lingual sides of the flaps. Irradiation was performed in non-contact mode in a constant distance of 1 mm during 30 s per site; Following local anesthesia, a full-thickness (muco-periosteal) access flap was elevated, granulation tissue was removed and direct instrumentation of the affected root surfaces was performed under the saline irrigation. Intrabony defects were filled with granules of allograft bone material and covered with a native porcine pericardial collagen membrane. The flaps were repositioned and sutured without any tension in order to achieve primary closure of the inter-dental area using a 5-0 mono-filament non-resorbable PTEF suturing material. On the 1st, 3rd, and 7th postoperative days, irradiation was carried out with a LED device with a wavelength of 626 nm in the near-infrared region at a dose of 20 mw/cm2 for 20 min with a total energy of 222 J; Following local anesthesia, a full-thickness (muco-periosteal) access flap was elevated, granulation tissue was removed and direct instrumentation of the affected root surfaces was performed under the saline irrigation. Intrabony defects were filled with granules of allograft bone material and covered with a native porcine pericardial collagen membrane. The flaps were repositioned and sutured without any tension in order to achieve primary closure of the inter-dental area using a 5-0 mono-filament non-resorbable PTEF suturing material. On the 1st, 3rd, and 7th postoperative days, topical ozone group received ozone application with an ozone generator at 80% concentration using probe #3 for 30 s per site
Intervention MeSH terms: Anti-Infective Agents; Anti-Bacterial Agents
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The present study is a parallel design randomized controlled clinical trial evaluating four different treatment approaches.
Masking: Single (Investigator)
Primary purpose: Treatment