Tissue Adhesive vs Silk Sutures After Mandibular Third Molar Extraction

Study Design and Participants

This randomized split-mouth controlled clinical trial enrolls patients attending the Department of Oral Surgery, Dental School, University of Turin, who require bilateral surgical extraction of impacted mandibular third molars. During the initial consultation, all participants undergo a comprehensive medical history assessment and clinical examination. Panoramic radiography (orthopantomogram, OPT) is prescribed as the first-level radiographic investigation, followed by cone-beam computed tomography (CBCT) when indicated to evaluate the anatomical relationship between the impacted teeth and adjacent structures. The degree of impaction and the expected surgical difficulty are assessed according to the Pell and Gregory classification. During the same appointment, patients receive detailed information regarding the study protocol and provide written informed consent. Two separate surgical appointments are scheduled at least one month apart.

Eligible participants are healthy adults (≥18 years) of either sex presenting with bilateral partial or complete impaction of mandibular third molars requiring surgical extraction, with comparable clinical and radiographic characteristics on both sides. Participants are required to be willing to comply with the study protocol and postoperative follow-up schedule. Exclusion criteria include age younger than 18 years, absence of bilateral impacted mandibular third molars requiring extraction, inability or unwillingness to attend follow-up visits, pregnancy, smoking, uncompensated systemic diseases, oncologic or hematologic disorders, and any condition known to directly or indirectly affect bone metabolism.

Sample Size Calculation

The sample size is calculated to provide 80% statistical power at a two-sided significance level of 5% (α = 0.05) for detecting differences in postoperative bleeding between the two flap closure techniques. Assuming an effect size (Cohen's d) of 0.675, derived from the study by Ghoreishian et al., a minimum of 18 participants is required for a split-mouth design. To compensate for an anticipated dropout rate of approximately 10%, the recruitment target is increased, resulting in a planned sample of 41 participants completing the study.

No interim analyses are planned.

Randomization

Because the two closure methods are visually distinguishable, blinding of the surgeon and participants is not feasible. A simple randomization sequence without blocking or stratification is generated using GraphPad Prism® software. Each participant receives a pseudonymized identification code, and allocation of the experimental and control sides is performed according to the randomization sequence. The sequence is generated by FME, participant enrollment is performed by LG and BL, and treatment allocation is carried out by PP.

Surgical Protocol

To minimize procedural variability, all surgical procedures are performed by the same experienced oral surgeon under standardized operative conditions. Before surgery, each participant rinses with a 0.2% chlorhexidine mouthwash for one minute. Local anesthesia is achieved through inferior alveolar and lingual nerve block using 2% mepivacaine, followed by buccal nerve infiltration with 2% mepivacaine containing epinephrine (1:100,000).

An envelope mucoperiosteal flap with a distal releasing incision is elevated using a periosteal elevator. Osteotomy is performed with a Lindemann bur under copious sterile saline irrigation using a surgical handpiece operating at approximately 40,000 rpm. Tooth sectioning is carried out whenever necessary to facilitate atraumatic removal. Following extraction, the socket is thoroughly debrided and irrigated with sterile saline solution.

In the control intervention, the flap is repositioned and stabilized with three interrupted 3/0 silk sutures. In the experimental intervention, flap closure is achieved using n-hexyl-cyanoacrylate tissue adhesive (Ifabond® Glue). During adhesive application, the surgical field is maintained completely dry using sterile gauze and suction, and the adhesive is carefully dispensed along the wound margins until complete polymerization is achieved.

Postoperative Management

All participants receive standardized postoperative instructions, including recommendations for a soft and cold diet, temporary avoidance of strenuous physical activity, and abstention from vigorous mouth rinsing during the first postoperative day. Pharmacological therapy consists of amoxicillin/clavulanic acid (875 mg/125 mg) administered every 12 hours for six days and ibuprofen 600 mg prescribed on demand, with a maximum dosage of one tablet every eight hours. Participants also receive standardized oral hygiene instructions, including twice-daily rinsing with 0.12% chlorhexidine mouthwash.

Participants attend follow-up visits during the first three postoperative days for assessment of postoperative bleeding. In the control group, suture removal is performed seven days after surgery.

Outcome Measures

The primary outcomes are postoperative bleeding, postoperative pain, and analgesic consumption.

Postoperative bleeding is assessed using a four-point Numerical Rating Scale (NRS; scores ranging from 0 to 3) and is recorded once daily during the first three postoperative days by a calibrated examiner. Pain intensity is assessed using the same four-point NRS and is self-recorded by participants daily for five consecutive postoperative days. To ensure consistency of reporting, each participant receives standardized verbal and written instructions together with reference charts illustrating the scoring system. Daily analgesic intake, including both the number of tablets consumed and the medication used, is recorded over the five-day observation period as an objective indicator of postoperative discomfort.

The secondary outcome is the immunological characterization of the healing socket seven days after surgery. Following suture removal in the control group and gentle irrigation of the extraction site with an equal mixture of saline solution and hydrogen peroxide, biological samples are collected from both experimental sites using sterile curettes and alveolar forceps without the need for local anesthesia. Samples are immediately transferred into 5-mL Eppendorf tubes containing sodium heparin solution and are stored at -80°C until analysis.

Immunological profiling is performed using the Bio-Plex Multiplex Immunoassay System (Bio-Rad Laboratories, Hercules, CA, USA) according to the manufacturer's instructions. Each specimen is analyzed in duplicate to ensure analytical reliability. Cytokine concentrations are quantified from standardized calibration curves and expressed as pg/mL. The panel includes interleukin (IL)-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-17, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-α (IFN-α), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α), allowing a comprehensive evaluation of the local inflammatory and immunological response associated with each flap closure technique.

No modifications to the study protocol or outcome measures are planned after trial initiation.

Inclusion criteria

• Adults aged 18 years or older.
• Healthy individuals (ASA I or II) with no history of uncontrolled systemic disease.
• Presence of bilateral partially or completely impacted mandibular third molars requiring surgical extraction.
• Comparable clinical and radiographic characteristics of both mandibular third molars.
• Ability and willingness to provide written informed consent.
• Willingness and ability to comply with the study protocol and attend all scheduled follow-up visits.

Exclusion criteria

• Age younger than 18 years.
• Absence of bilateral impacted mandibular third molars requiring surgical extraction.
• Pregnancy or breastfeeding.
• Current smoking.
• Uncontrolled systemic diseases or medical conditions affecting wound healing or bone metabolism.
• Oncological or hematological disorders.
• Inability or unwillingness to provide informed consent or comply with the study protocol and follow-up schedule.