Effect of Injectable Hyaluronic Acid (HYADENT BG (HA)) on Bone Healing in Extraction Sockets
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.
Study Overview
Status
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Tamimi
- Phone Number: 00962795036670
- Email: zztamimi@just.edu.jo
Study Locations
-
-
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Irbid, Jordan, 11196
- Recruiting
- Higher specialty training center
-
Contact:
- rola Habashneh, Professor
- Phone Number: 0096227201000
- Email: raalhabashneh@just.edu.jo
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Placebo Comparator: placebo extraction side
Surgical extraction of wisdom tooth with placebo administration inside the extraction site using collagen sponge
|
A standardized surgical procedure was performed by a single experienced surgeon (ZA).
Under strict aseptic conditions, an inferior alveolar nerve block with buccal infiltration, was given using lidocaine HCl 2% with epinephrine 1:100,000 (Cook-Waite, Rochester, NY).
A mucoperiosteal envelope flap was utilized for all surgeries.
Bone removal and tooth sectioning were performed as deemed necessary using a low-speed handpiece under copious saline irrigation.
After tooth removal, HA gel (Hyadent) was placed inside the extraction socket and covered with collagen sponge in the test sockets, while only coverage with collagen sponge was placed in the control sockets.
Subsequently, flap closure was achieved using 3-0 silk sutures
After 6 weeks, core biopsies are taken from both sides. Under local anesthesia, the core biopsies sre taken without reflection of a flap, using a graded trephine bur (MCT, Korea) of 3 mm diameter (which is not invasive or having any complication) for later histological evaluation. Specimens harvested from each patient are fixed in 10% formalin, then decalcified using 10% hydrochloric acid. After processing, 5 micrometer sections are prepared and stained with hematoxylin and eosin stain (H&E). Digital images are acquired from each section at a magnification of × 40. ImageJ 1.52a software (National Institute of Health, Bethesda, Maryland, USA) is used to calculate the percentage of woven bone area within selected regions of interest (ROI) in each image, utilizing the color thresholding feature. To ensure that measurements are valid, 3 measurements are made for each of the hard tissue and soft tissue components, and for the total area of the ROI in pixels. |
|
Experimental: experimental extraction side
Surgical extraction of wisdom tooth with placebo administration inside the extraction site using hyaluronic acid gel
|
A standardized surgical procedure was performed by a single experienced surgeon (ZA).
Under strict aseptic conditions, an inferior alveolar nerve block with buccal infiltration, was given using lidocaine HCl 2% with epinephrine 1:100,000 (Cook-Waite, Rochester, NY).
A mucoperiosteal envelope flap was utilized for all surgeries.
Bone removal and tooth sectioning were performed as deemed necessary using a low-speed handpiece under copious saline irrigation.
After tooth removal, HA gel (Hyadent) was placed inside the extraction socket and covered with collagen sponge in the test sockets, while only coverage with collagen sponge was placed in the control sockets.
Subsequently, flap closure was achieved using 3-0 silk sutures
After 6 weeks, core biopsies are taken from both sides. Under local anesthesia, the core biopsies sre taken without reflection of a flap, using a graded trephine bur (MCT, Korea) of 3 mm diameter (which is not invasive or having any complication) for later histological evaluation. Specimens harvested from each patient are fixed in 10% formalin, then decalcified using 10% hydrochloric acid. After processing, 5 micrometer sections are prepared and stained with hematoxylin and eosin stain (H&E). Digital images are acquired from each section at a magnification of × 40. ImageJ 1.52a software (National Institute of Health, Bethesda, Maryland, USA) is used to calculate the percentage of woven bone area within selected regions of interest (ROI) in each image, utilizing the color thresholding feature. To ensure that measurements are valid, 3 measurements are made for each of the hard tissue and soft tissue components, and for the total area of the ROI in pixels. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Postoperative Pain Intensity
Time Frame: 12 hours (postoperative day 1), postoperative day 3, and postoperative day 7. Units of measure is VAS score (1-10).
|
Postoperative pain intensity 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 following mandibular third molar extraction.
|
12 hours (postoperative day 1), postoperative day 3, and postoperative day 7. Units of measure is VAS score (1-10).
|
|
Alveolar Socket Bone Healing
Time Frame: 6 weeks after tooth extraction. units of measure is percentage of woven bone area (%)
|
Alveolar socket bone healing will be evaluated histologically by quantifying the percentage of woven bone formation within the extraction socket.
Core biopsies will be obtained six weeks post-extraction and analyzed using digital histomorphometry.
The percentage of woven bone area within predefined regions of interest will be calculated using ImageJ software.
|
6 weeks after tooth extraction. units of measure is percentage of woven bone area (%)
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Radiographic Assessment of Socket Healing
Time Frame: Preoperative baseline and 6-8 weeks post-extraction
|
Radiographic socket healing will be assessed descriptively using orthopantomogram (OPG) imaging.
Standardized radiographs will be obtained preoperatively and approximately six to eight weeks post-extraction to evaluate changes in socket radiodensity.
|
Preoperative baseline and 6-8 weeks post-extraction
|
Collaborators and Investigators
Investigators
- Study Chair: Rola Habashneh, Professor, Jordan University of Science and Technology
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- 35/175/2024
- 644/2024 (Other Grant/Funding Number: Jordan University of Science and Technology)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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