Regenerative Gel (Emdogain®) for Healing After Wisdom Tooth Extraction

Aristotle University Of Thessaloniki70 enrolled

Overview

This study investigates whether the intraoperative application of a specialized regenerative gel (Emdogain®) can improve the periodontal health of the mandibular second molar by preventing or reducing the formation of tissue defects after the surgical removal of an adjacent impacted lower wisdom tooth. Surgical extraction of a lower wisdom tooth frequently leaves a deep pocket or a permanent hard and/or soft tissue defect on the back side of the neighboring second molar. This defect compromise the surrounding tissues and predispose the healthy second molar to future complications like root caries, dentin hypersensitivity, or localized gum disease. While most existing treatments address these defects after they have formed, this trial evaluates a site-specific preventive approach during the extraction process itself. The study will involve 70 systemically healthy adults (ages 18-45) requiring surgical removal of a horizontally or mesially oriented impacted lower third molar. Participants will be randomized into two equal groups: The Test Group: Will receive root conditioning with PrefGel and a single application of Emdogain® gel directly to the root surface and socket immediately after tooth removal. The Control Group: Will undergo identical surgery but will follow a natural, spontaneous healing process without the application of any biomaterials. The main objective is to measure changes in Clinical Attachment Level (CAL) at the distal aspects of the second molar using stable vertical anatomical reference points over a 6-month period. The trial will also monitor secondary healing parameters, including probing pocket depths, gum recession, radiographic bone level changes using standardized jigs, postoperative pain, swelling, and early tissue healing dynamics.

The primary objective of this two-center, parallel-group, randomized clinical trial is to investigate whether the intraoperative application of Enamel Matrix Derivative (EMD) can improve the long-term periodontal health of the mandibular second molar by preventing or minimizing the formation of distal tissue defects following third molar surgery. While the regenerative properties of EMD are well-documented in periodontology, the novelty of this study lies in its prophylactic, site-specific usage at the immediate time of extraction. Methodology and Standardization To maximize data reproducibility and minimize measurement errors, the study incorporates the following rigorous standardization protocols: Anatomical Selection: To control for surgical site variables and baseline defect morphology, inclusion is strictly limited to patients presenting with horizontally or mesially oriented impacted mandibular third molars. Clinical Measurement Protocol: Clinical parameters are recorded at seven distinct sites around the mandibular second molar: mesio-buccal, mid-buccal, disto-buccal, mesio-lingual, mid-lingual, disto-lingual, and mid-distal. Because the adjacent third molar, the surrounding soft tissue, and limited clinical visibility obscure the distal cementoenamel junction (CEJ) preoperatively, stable and reproducible vertical anatomical landmarks are utilized as reference points for all measurements adjacent to the extraction defect. The disto-buccal site is measured from the distal-buccal cusp tip; the disto-lingual site is measured from the distal-lingual cusp tip; and the mid-distal site is measured from the permanent occlusal (masticatory) surface of the second molar. The remaining four sites (mesio-buccal, mid-buccal, mesio-lingual, and mid-lingual) will be measured from the standard CEJ landmark as usual. Examiner Calibration: All clinical measurements are performed by a single investigator who undergoes intensive pre-study calibration sessions targeting an intra-examiner intraclass correlation coefficient (ICC) ≥0.85, with scheduled recalibration to prevent measurement drift over time. Radiographic Calibration and Alignment: To eliminate radiographic distortion and magnification errors, a calibration sphere (metal ball) with a fixed, known diameter of 5 mm is attached to the radiographic setup. Digital image analysis software utilizes the true dimensions of this 5 mm ball to calculate the precise, absolute bone level distances via a standard proportional scale (rule of three). All radiographs are captured using the long-cone paralleling technique, standardized via a customized film-positioning device and repeatable radiographic jigs to ensure identical alignment across all time points. Study Arms and Follow-up: Seventy systemically healthy participants (ages 18-45) are randomized to either the Test Arm (debridement, root conditioning with PrefGel, and site-specific application of Emdogain® gel) or the Control Arm (identical surgical protocol allowing for spontaneous healing via a natural blood clot). Both groups receive standardized postoperative pharmacological and oral hygiene care. Early soft-tissue healing and patient-reported outcomes are monitored during the first week, while definitive soft- and hard-tissue periodontal remodeling is evaluated at 6 months postoperatively.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 35 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Healthy adult patients aged 18 to 35 years old (ASA I or II). * Presence of an asymptomatic, partially or fully impacted mandibular third molar requiring surgical extraction. * The third molar impaction must be mesioangular or horizontal, with its crown in direct physical contact with the adjacent second molar, as assessed by a preoperative panoramic radiograph. * The adjacent mandibular second molar must be vital, fully erupted, and structurally sound (free of extensive dental caries or prosthetic crowns). * Patients must demonstrate an adequate level of overall oral hygiene and gingival health (e.g., Full-Mouth Plaque Index \< 20% and Full-Mouth Bleeding Score \< 20% following initial prophylaxis and oral hygiene instructions). * Willingness to comply with postoperative instructions and adhere to the scheduled follow-up visits. * Ability to understand the study procedures and voluntarily sign the informed consent form. Exclusion Criteria * Presence of systemic diseases or conditions that could compromise wound healing or periodontal health (e.g., uncontrolled diabetes mellitus, autoimmune disorders). * Current or recent use of medications known to affect bone metabolism or wound healing (e.g., bisphosphonates, long-term systemic corticosteroids, immunosuppressants). * History of heavy smoking (e.g., \>10 cigarettes per day) or use of smokeless tobacco products. * Pregnant or lactating females. * Diagnosis of periodontitis (Stage II, III, or IV) affecting the remaining dentition, excluding the localized defect associated with the impacted third molar. * Presence of active acute infection (e.g., purulent pericoronitis) or radiolucent pathologic lesions extending beyond the normal follicular space (e.g., dentigerous cysts) that would significantly alter the baseline bony defect morphology. * Known allergy or hypersensitivity to any of the medications utilized in the surgical or postoperative protocol (e.g., local anesthetics, prescribed antibiotics, or analgesics). * Previous orthodontic treatment utilizing bands on the mandibular second molars that could have affected the periodontal attachment.

Outcomes

Primary Outcomes

Change in Clinical Attachment Level (CAL)

Clinical Attachment Level (CAL) is a measurement of periodontal health indicating the position of the soft tissue attachment on the tooth root, measured in millimeters (mm) using a calibrated periodontal probe. It will be recorded at seven distinct sites on the mandibular second molar. For the distal sites directly adjacent to the extraction socket, fixed coronal reference points will be used to calculate relative CAL, as the cementoenamel junction (CEJ) is often compromised by the impaction. For the remaining four sites on the second molar, the standard CEJ will be utilized as the fixed anatomical reference point. A reduction in the distance from these reference points to the base of the periodontal pocket over time indicates a clinical gain of tissue attachment and successful healing.

Time frame: Baseline (immediately prior to surgery) and 6 months post-surgery

Secondary Outcomes

Change in Radiographic Alveolar Bone Level

The vertical distance from the CEJ to the alveolar bone crest at the distal aspect of the mandibular second molar. Measurements will be conducted using standardized intraoral radiographs taken with the parallel cone technique and an individualized occlusal jig to ensure precise spatial reproducibility. The images will be calibrated using radiopaque spheres to account for magnification and will be evaluated by three independent, masked observers.

Time frame: Baseline (immediate post-operative) and 6 months post-surgery

Change in Probing Pocket Depth (PPD)

Distance from the free gingival margin to the base of the periodontal pocket, measured in millimeters (mm) using a calibrated periodontal probe at the seven designated sites around the mandibular second molar (as defined in the primary outcome).

Time frame: Baseline (immediately prior to surgery) and 6 months post-surgery

Change in Gingival Recession (REC)

Distance from the cementoenamel junction (CEJ) or fixed coronal reference point to the free gingival margin, measured in millimeters (mm) using a calibrated periodontal probe at the seven designated sites around the mandibular second molar.

Time frame: Baseline and 6 months post-surgery

Change in Bleeding on Probing (BOP)

A dichotomous index (yes/no) assessing the presence or absence of bleeding after periodontal probing at the six sites around the mandibular second molar. It acts as a clinical indicator of localized tissue inflammation.

Time frame: Baseline and 6 months post-surgery

Change in Plaque Index (PI)

Assessment of the presence or absence of supragingival dental plaque on the surfaces of the mandibular second molar, recorded to monitor the patient's oral hygiene compliance throughout the healing phase.

Time frame: Baseline and 6 months post-surgery

Postoperative Facial Oedema

Assessment of postoperative extraoral swelling. This is quantified by measuring the distances between specific anatomical facial landmarks using a flexible measuring tape.

Time frame: Baseline (pre-operative) and 7 days post-surgery

Postoperative Trismus (Maximum Interincisal Opening)

Measurement of maximum mouth opening capability to assess postoperative trismus. It is recorded as the maximum vertical distance in millimeters (mm) between the incisal edges of the maxillary and mandibular central incisors.

Time frame: Baseline (pre-operative) and 7 days post-surgery

Postoperative Pain

Patient-reported postoperative pain intensity evaluated daily using a Numeric Rating Scale (NRS) ranging from 0 (no pain) to 10 (worst imaginable pain). Additionally, the total number of analgesic tablets consumed by the patient will be recorded via a patient diary.

Time frame: Daily for the first 7 days post-surgery

Oral Health-Related Quality of Life (OHIP-14)

Patient-reported outcome assessing the impact of the surgery on daily life using the validated 14-item Oral Health Impact Profile (OHIP-14) questionnaire. Total scores range from 0 to 56, with higher scores indicating a greater negative impact on the patient's quality of life.

Time frame: Baseline (pre-operative), 7 days post-surgery and 6 months post-surgery

Change in Sleep Quality

Assessment of postoperative sleep quality and disturbances using the validated Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8a (PROMIS-SD SF 8a). This instrument specifically evaluates sleep quality over a 7-day recall period. It consists of 8 items, yielding a total score ranging from 8 to 40. Higher scores indicate greater sleep disturbance and a worse postoperative sleep experience.

Time frame: Baseline (pre-operative) and 7 days post-surgery

Regenerative Gel (Emdogain®) for Healing After Wisdom Tooth Extraction

Overview

Conditions

Interventions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts