Hyalouronic Acid and Periodontal Surgery

March 13, 2026 updated by: Aristotle University Of Thessaloniki

Healing Effect of Hyaluronic Acid Gel in Conjunction With Periodontal Surgery. A Randomized Controlled Clinical and Biomarkers Study

This study investigated the effectiveness of hyaluronic acid gel in enhancing soft tissue healing after periodontal surgery for residual pockets (5-8 mm). A 3-month prospective, randomized controlled trial included 26 patients from Aristotle University's Postgraduate Periodontology Clinic who had completed initial periodontal therapy and exhibited at least one residual pocket.

Participants were randomly assigned to an experimental group (receiving 0.6 ml hyaDENT BG hyaluronic acid gel) or a control group (receiving 0.6 ml saline). Before surgery, gingival crevicular fluid (GCF) samples were collected for inflammatory and healing biomarkers (PGE-2, MMP-9, IL-1β, VEGF, EGF), analyzed using ELISA. Surgery was performed at sites with persistent pockets, and follow-ups occurred at 14 days and 3 months postoperatively.

Healing was assessed using the Landry, Turnbull, and Howley Wound Healing Index (WHI). Clinical parameters, including probing pocket depth (PPD), bleeding on probing (BoP), clinical attachment level (CAL), and plaque index (PI), were measured at 3 months, with treatment success defined as PPD ≤4 mm without BoP. Patient-reported outcomes, such as pain, swelling, chewing, speech, and aesthetics, were evaluated using a Visual Analog Scale (VAS).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The current study aimed to investigate the effectiveness of hyaluronic acid gel in accelerating soft tissue healing following periodontal surgery for the treatment of residual periodontal pockets with a depth of 5-8 millimeters.

A prospective, randomized controlled clinical study with a duration of 3 months was designed. Twenty six (26) patients attending the Postgraduate Periodontology Clinic of the Dental School at Aristotle University of Thessaloniki (AUTH). These patients had completed Steps 1 and 2 of initial causative periodontal therapy and had at least one residual periodontal pocket with a depth of 5-8 mm during the re-evaluation (according to the 2018 classification of periodontal and peri-implant diseases). Clinical measurements and radiographic evaluation were performed using the parallel technique, and patients received oral hygiene instructions as part of the initial assessment. Surgical intervention was scheduled two weeks later at sites showing a periodontal pocket depth of 5-8 mm during re-evaluation. The participants were randomly assigned to one of two groups: the experimental group, which received surgical treatment with 0.6 ml of hyaDENT BG hyaluronic acid gel inside the flap, and the control group, which received surgical treatment with 0.6 ml of normal saline (placebo). Prior to surgery, two sterile paper strips (Periostrips) were used to collect gingival crevicular fluid (GCF) samples for inflammatory biomarkers (PGE-2, MMPs-9, IL-1β) and markers for angiogenesis and epithelial cell proliferation (VEGF, EGF). Biomarker concentrations were assessed using the Elisa technique. The patients were followed up on the 14th day and at 3 months post-surgery. GCF samples were taken from the same periodontal pocket on the 14th day (after suture removal) for the evaluation of VEGF and EGF, and at 3 months for the study of PGE-2, MMP-9, and IL-1β. Clinical re-assessments were conducted at 3 months, including measurements of pocket depth (PPD), bleeding on probing (BoP), clinical attachment level (CAL), and plaque index (PI). Treatment success was defined as a pocket depth of ≤4 mm without bleeding on probing at the initial lesion sites. Soft tissue healing was evaluated macroscopic using the Landry, Turnbull, and Howley Wound Healing Index (WHI). Postoperative pain, swelling, chewing and speaking ability, and appearance were assessed using a Visual Analog Scale (VAS).

Study Type

Interventional

Enrollment (Actual)

26

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Greece
    • Central Macedonia
      • Thessaloniki, Central Macedonia, Greece, 54124
        • Aristotle University of Thessaloniki, School of Dentistry

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • the presence of at least one residual pocket with depth 5-8mm at the follow - up examination, after the completion of Steps 1 and 2 of the initial etiological periodontal therapy.

Exclusion Criteria:

  • severe systematic disease of patients by which a surgical procedure cannot be performed (e.g., uncontrolled diabetes, chemotherapy, immunosuppressive therapy, use of bisphosphonates)
  • previous periodontal surgery at the site of the lesion
  • antibiotic intake in the last one month before treatment
  • patients who smoke more than 10 cigarettes per days
  • use drugs or alcohol
  • women in pregnancy or lactation period
  • periodontal lesions indicated for regeneration (3-walled, craters) were excluded from the study and were threated accordingly

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Periodontal surgery and Hyalouronic acid
Test Group (Group HA): periodontal surgery and application of 0.6 ml of hyaDENT BG hyaluronic acid gel
Procedure: Hyalouronic Acid
Periodontal surgery and Hyalouronic acid
Placebo Comparator: Periodontal surgery and saline solution/ placebo
Control group (Group C):periodontal surgery and application of 0.6 ml of saline solution/placebo.
Procedure: Saline solution / placebo
Periodontal surgery and saline solution/ placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Periodontal pocket depth - change in millimeters (mm)
Time Frame: Baseline to 3 months
Periodontal pockrt depth is measured using a periodontal probe at six sites per tooth. (Periodontal probe UNC15, Hu-Friedy, Rotterdam, the Netherlands)
Baseline to 3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Attachment Level-CAL in millimeters (mm).
Time Frame: Baseline to 3 months
Clinical Periodontal Marker: The distance in mm from the CEJ to the gingival margin (Periodontal probe UNC15, Hu-Friedy, Rotterdam, the Netherlands) Time Frame: 6 months
Baseline to 3 months
Bleeding on Probing-BoP - Change in percentage
Time Frame: baseline to 3 months
Clinical Periodontal Marker: Bleeding after slight pressure by a standardized (dimensions and shape) periodontal probe with a controlled (∼0.25 N) force to the apical end of the sulcus (Periodontal probe UNC15, Hu-Friedy, Rotterdam, the Netherlands)
baseline to 3 months
Plaque Index-PI - Change in percentage
Time Frame: baseline to 3 months
PI : Assessment of plaque accumulation at six sites per tooth. Percentage of sites with plaque on probing.
baseline to 3 months
Interleukin-1 beta-IL-1β in pg/ml
Time Frame: baseline to 3 months

IL-1β: Gingival crevicular fluid levels of Interleukin-1 beta (IL-1β) using perio strips into the gingival sulcus.

Unit of Measure: pg/mL
baseline to 3 months
Vascular Endothelial Growth Factor-VEGF in pg/ml
Time Frame: 14 days post-treatment

VEGF: Gingival crevicular fluid levels of Vascular Endothelial Growth Factor using perio strips into the gingival sulcus.

Unit of Measure: pg/mL
14 days post-treatment
Early Wound Healing Index by Landry, Turnbull, and Howley in score range 0-5
Time Frame: 14 days post-treatment

Early Wound Healing Index Score:

Soft tissue healing assessed using the Early Wound Healing Index by Landry, Turnbull, and Howley. Scores range from 0 to 5. Higher scores indicate better healing.

Unit of Measure: Score (0 worst-5 better )
14 days post-treatment
Patient-Reported treatment Experience in VAS score
Time Frame: 14 days post-treatment
Patient-Reported treatment Experience Overall treatment experience assessed using a Visual Analog Scale (VAS). Scores range from 1 to 10. Higher scores indicate better patient-reported experience. Unit of Measure:1(worst)-10(better)
14 days post-treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Aristotle University Of Thessaloniki

Investigators

  • Principal Investigator: Elpiniki Vlachodimou, MSc, Aristotle University of Thessaloniki
  • Study Director: Aikaterini - Elisavet Doufexi, Assistant Professor, Aristotle University of Thessaloniki
  • Study Director: Ioannis Vouros, Professor, Aristotle University of Thessaloniki

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 16, 2024

Primary Completion (Actual)

February 19, 2025

Study Completion (Actual)

May 19, 2025

Study Registration Dates

First Submitted

January 30, 2026

First Submitted That Met QC Criteria

March 13, 2026

First Posted (Actual)

March 16, 2026

Study Record Updates

Last Update Posted (Actual)

March 16, 2026

Last Update Submitted That Met QC Criteria

March 13, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 22/27.03.2024

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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