Polynucleotide + Hyaluronic Acid Gel With Xenogeneic Graft for Intrabony Periodontal Defects

Official title

Effects of the Combination of a Polynucleotide and Hyaluronic Acid-Based Gel With Xenogeneic Bone Graft in the Treatment of Intrabony Defects in Patients With Periodontitis: a Randomized Controlled Clinical Trial.

Overview

Over the last 30 years, the prevalence of periodontitis (PE) has increased substantially, including among younger populations, highlighting the need to improve the management of this condition as a chronic disease and to develop techniques that favor its control and stability in the short and long term. After non-surgical periodontal therapy (NSPT), the first phase of PE treatment, residual periodontal pockets may persist, often associated with intraosseous defects, which compromise the tooth's prognosis and are associated with disease progression and increased treatment complexity. Surgical treatment of intrabony defects often results in the formation of long junctional epithelium, weakly attached to the root surface, since true regeneration of periodontal tissues is an unpredictable event and depends on complex biological processes. In recent decades, various biomaterials have been proposed as aids to open-flap debridement (OFD) in the surgical treatment of intrabony defects, with the aim of promoting periodontal regeneration, enhancing clinical results and favoring treatment prognosis. Recently, the combination of polynucleotides (PN) and hyaluronic acid (HA) has emerged as a promising auxiliary strategy to promote periodontal regeneration, due to its biological potential in stimulating cell growth and increasing cell viability. The aim of this controlled, randomized, parallel-group clinical study is to compare OFD alone with its association with xenogenous bone graft or xenogenous bone graft plus gel containing PN/HA in the surgical treatment of intrabony defects in patients with PE (stages III or IV, grades B or C). The patients will be randomly divided into three experimental groups (n=22): control (C), xenogeneic bone graft (XENO) and xenogeneic bone graft plus gel containing PN/HA (R-XENO). The patients will receive NSPT, and after eight weeks will undergo surgical procedures to treat the intrabony defects (baseline). Clinical, radiographic, tomographic and immunological periodontal parameters will be assessed at baseline and after 12 months. The wound healing index will be recorded 1, 2 and 6 weeks after the surgical procedure. Patient-centered outcomes will be assessed by means of a visual analog scale (VAS), applied two weeks after the surgical procedure, and oral health-related quality of life (OHRQoL) questionnaires, applied at the beginning of the study and after 6 and 12 months. At the start of the study and after 6 and 12 months, anthropometric data will be collected, blood pressure (BP) will be measured and questionnaires will be applied to survey socio-demographic and nutritional parameters. The data obtained will be statistically analyzed (p\<0.05).

Detailed description

This controlled, randomized, parallel-group clinical study aims to compare open-flap debridement alone with its association with xenogeneic bone graft or xenogeneic bone graft plus gel containing polynucleotides (PN) and hyaluronic acid (HA) in the surgical treatment of intrabony defects in patients with periodontitis (stages III or IV, grades B or C), based on clinical, immunologic, radiographic/tomographic parameters and patient-centered outcomes.

The sample size was calculated using the primary variable clinical attachment level (CAL), considering a mean difference of 1 mm between the experimental groups as the minimum value and a standard deviation of 0.91. Considering β = 80% and α = 5%, the required sample size was 18 patients for each experimental group, with each patient contributing a single defect. Considering a dropout of 20%, the number was increased to 22 patients per experimental group, making a total of 66 patients.

Patients who meet the inclusion criteria will be randomly assigned to one of three experimental groups (n=22) in a 1:1 allocation ratio: Group C (Control), including intrabony defects treated with open flap debridement alone; Group XENO, including open flap debridement associated with xenogeneic bone grafting; and Group R-XENO, including open flap debridement associated with xenogeneic bone grafting and a PN/HA-containing gel. Randomization will be performed using software, which will identify each participant by a numerical code. Group allocation will be carried out on the day of surgery by the study coordinator.

Surgical treatment: After local anesthesia using an infiltration or nerve block technique with a sterile injectable solution of 2% mepivacaine hydrochloride (20 mg/mL) and 1:100,000 epinephrine (10 µg/mL), intrasulcular incisions will be made on the buccal and lingual/palatal aspects using a 15C surgical blade (Stainless Steel Surgical Blades, Swann-Morton®, Sheffield, England), extending one tooth mesially and one tooth distally to the tooth associated with the defect. A full-thickness flap will be carefully elevated on the buccal and lingual/palatal sides to expose 2 to 3 mm of the alveolar crest. Meticulous debridement of the defect will be performed, along with the removal of subgingival biofilm and calculus using ultrasonic combined with manual instruments, followed by irrigation with sterile saline solution. The defects will be filled as follows: with blood clot only in the group C; with xenogeneic bone graft (Geistlich Bio-Oss®, Geistlich Pharma AG, Wolhusen, Switzerland) in the XENO group; and with xenogeneic bone graft (Geistlich Bio-Oss®) plus PN/HA-containing gel (REGENFAST®, Geistlich Pharma AG, Wolhusen, Switzerland) in the R-XENO group. Primary soft tissue closure was achieved by interrupted mattress suture technique with non-resorbable monofilament polyamide 5-0 sutures (Soft Blue®, Techsuture, Bauru, SP, Brazil).

Outcome assessment will be conducted at predefined time points. The primary outcome is clinical attachment level (CAL). Secondary outcomes include probing depth (PD); radiographic and tomographic measures of bone fill and defect resolution; quantitative analysis of biomarkers related to tissue neoformation (PDGF-BB, VEGF, BMP-2); early wound healing assessed by standardized indices; and patient-reported outcomes, including pain perception and oral health-related quality of life.

Interventions

• Device Polynucleotide and hyaluronic acid-based gel
  The polynucleotide and hyaluronic acid-based gel will be applied in combination with a xenogeneic bone graft to fill the intrabony defects.
• Other Control
  Intrabony defects treated with open flap debridement alone
• Device Xenogeneic bone graft
  The xenogeneic bone graft will be applied to fill the intrabony defects.

Primary outcome measures

• Clinical Attachment Level (CAL) [Time frame: Baseline and 12 months]

Secondary outcome measures (12)

• Probing depth (PD) [Time frame: Baseline and 12 months]
• Changes in the alveolar bone crest [Time frame: Baseline and 12 months]
• Radiographic defect depth [Time frame: Baseline and 12 months]
• Vertical bone loss [Time frame: Baseline and 12 months]
• Tomographic vertical bone loss [Time frame: Baseline and 12 months]
• Buccolingual width of the defect [Time frame: Baseline and 12 months]
• Platelet-derived growth factor (PDGF)-BB [Time frame: Baseline and 12 months]
• Vascular endothelial growth factor (VEGF) [Time frame: Baseline and 12 months]
• Bone morphogenetic protein (BMP)-2 [Time frame: Baseline and 12 months]
• Wound Healing Index (WHI). [Time frame: 1, 2 and 6 weeks]
• Visual Analogue Scale [Time frame: 2 weeks]
• Oral Health Impact Profile (OHIP-14) questionnaire [Time frame: Baseline, 6 and 12 months]

Eligibility criteria

Inclusion criteria

• ≥ 18 years of age;
• diagnosis of periodontitis stage III or IV, grade B or C (Chapple et al., 2018; Papapanou et al., 2018);
• full-mouth plaque score (FMPS) and full-mouth bleeding score (FMBS) of ≤ 20%;
• presence of a 2- or 3-wall intrabony defect with a depth ≥ 3 mm and probing depth and clinical attachment level ≥ 5 mm in the interproximal region of a single- or multi-rooted tooth;
• pulp vitality or satisfactory endodontic treatment in the tooth to be treated;
• at least 1 mm of keratinized tissue on the buccal surface of the tooth to be treated.

Exclusion criteria

• presence of furcation involvement associated with the intrabony defect;
• presence of systemic conditions that may affect the progression of periodontitis or the response to its treatment;
• long-term use of anti-inflammatory or immunosuppressive medications;
• use of antimicrobials within the last 6 months;
• continuous use of mouthwashes containing antimicrobial agents within the last 6 months;
• need for prophylactic antibiotic therapy for routine dental procedures;
• current or past tobacco use within the last 5 years;
• pregnancy;
• breastfeeding.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Brazil · 1 center

• Ribeirão Preto School of Dentistry, University of São Paulo — Ribeirão Preto

Identifiers

NCT: NCT07522684 · 95039026.0.0000.5419 · MTA #25-030

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗