Complications such as postoperative pain and delayed socket healing are relatively common following surgical extraction of mandibular third molars. Various biomaterials have been investigated to enhance wound healing and reduce postoperative morbidity. Hyaluronic acid (HA) has demonstrated anti-inflammatory and regenerative properties that may improve both soft and hard tissue healing.

The aim of this study is to evaluate the effect of topical hyaluronic acid on postoperative pain and alveolar socket bone healing following surgical extraction of mandibular third molars. A prospective, randomized, controlled clinical trial with a split-mouth design will be conducted. Twenty patients requiring bilateral mandibular third molar surgical extraction will be enrolled. In each patient, one extraction socket will receive hyaluronic acid combined with a collagen sponge, while the contralateral socket will receive a collagen sponge alone, according to random allocation. Postoperative pain will be assessed using a visual analogue scale, and socket healing will be evaluated radiographically and histologically.

This study is designed as a prospective, randomized, controlled clinical trial with a split-mouth design to assess the effect of topical hyaluronic acid on postoperative pain and alveolar socket bone healing following surgical extraction of mandibular third molars. The study will be conducted at the Oral and Maxillofacial Surgery and Preventive Dentistry clinics, Faculty of Dentistry, Jordan University of Science and Technology, Irbid, Jordan.

A total of 20 patients requiring bilateral surgical extraction of mandibular third molars will be enrolled. All participants will receive verbal and written information regarding the study procedures, and written informed consent will be obtained prior to participation. Randomization will be performed using a closed-envelope method. In each patient, one extraction site will be randomly allocated to receive hyaluronic acid gel combined with a collagen sponge (test site), while the contralateral site will receive a collagen sponge alone (control site).

The hyaluronic acid used in this study is a low-molecular weight sodium hyaluronate gel (Hyadent®, BioScience GmbH, Ransbach-Baumbach, Germany), supplied in sterile 1 mL syringes with blunt angulated cannulas. Each syringe contains sodium hyaluronate (14.0 mg), sodium chloride (6.9 mg), and water for injection. The formulation has modified viscosity and a short resorption time, allowing rapid absorption by the surrounding tissues.

All surgical procedures will be performed by a single experienced oral surgeon under standardized conditions. Preoperative evaluation includes medical and dental history, clinical examination, and panoramic radiography. Local anesthesia will be administered using an inferior alveolar nerve block with buccal infiltration of 2% lidocaine with 1:100,000 epinephrine. A standardized mucoperiosteal envelope flap will be raised for all procedures. Bone removal and tooth sectioning will be carried out when necessary using a low-speed handpiece under copious sterile saline irrigation.

After tooth removal, hyaluronic acid gel will be placed into the extraction socket at the test site and covered with a collagen sponge. Control sites will receive a collagen sponge alone. Primary closure will be achieved using 3-0 silk sutures. All patients will receive standardized postoperative instructions and medications. Sutures will be removed on postoperative day seven.

Postoperative pain will be assessed using a visual analogue scale (VAS) ranging from 1 (no pain) to 10 (worst pain imaginable). Participants will record pain scores at standardized time points: 12 hours after surgery (postoperative day 1), postoperative day 3, and postoperative day 7.

Radiographic assessment of socket healing will be performed using orthopantomogram (OPG) imaging in a randomly selected subgroup of participants approximately eight weeks after extraction. Radiographs will be obtained using standardized exposure parameters and processed under controlled conditions to ensure consistency.

Histological evaluation of socket healing will be conducted six weeks after extraction. Core biopsies will be obtained from both extraction sites under local anesthesia without flap reflection using a 3 mm diameter graded trephine bur. Harvested specimens will be fixed in formalin, decalcified, processed, and stained with hematoxylin and eosin. Digital images will be analyzed using image analysis software to calculate the percentage of woven bone within predefined regions of interest.

Statistical analysis will be performed using Statistical Package for the Social Sciences (SPSS) software. Descriptive statistics will be calculated for all variables. Comparative analyses will be conducted to evaluate differences in postoperative pain and woven bone formation between test and control sites, as well as changes in pain intensity over time.

Inclusion Criteria:

Male and female participants aged 18 to 35 years

Presence of bilateral impacted mandibular third molars classified as Pell and Gregory Class II, Position B

Classified as American Society of Anesthesiologists (ASA) Physical Status I

Absence of active local infection at the surgical site (e.g., no swelling, trismus, hyperthermia)

Ability to maintain adequate oral hygiene

Ability to understand and provide written informed consent

Ability to read and understand Arabic or English

Willingness to comply with study procedures and follow-up visits

Exclusion Criteria:

History of systemic diseases such as diabetes mellitus, hypertension, gastric ulcer, or other significant medical conditions

Presence of severe or chronic illness requiring frequent hospitalization

Pregnant or breastfeeding individuals

History of cognitive or motor impairment that may interfere with study participation

Use of anti-inflammatory or analgesic medications within two weeks before surgery

Known allergy or hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs)

Current smoker

Use of anticoagulant therapy

Any condition that, in the investigator's judgment, may interfere with healing or study outcomes

The data of the participants collected are clinical and we should take their consent for any future studies. As our IRB approval is limited to this study, we cant share these data.

Double (Participant, Investigator)