Influence of Hyaluronic Acid in the Healing of Palatal Donor Sites During Free Gingival Graft Procedures (HA Palate)

March 4, 2026 updated by: Pier Paolo Poli, University of Milan

Efficacy of Cross-linked Hyaluronic Acid in Improving Healing After Free Gingival Graft: a Randomized Controlled Clinical Trial

The goal of this study is to evaluate the use of a gel containing cross-linked hyaluronic acid (xHyA) at the palatal donor site following soft tissue harvesting procedures. The main questions it aims to answer are: 1) Does the use of xHyA improve post-operative patient morbidity?; 2) Does the use of xHyA improve palatal donor site healing? Researchers will compare xHyA topically applied at the palatal donor site to a negative control to see if xHyA works to minimize participants' morbidity and improve clinical healing.

Participants will be equally distributed into two groups, half of them receiving xHyA. Participants will fill a visual analogue scale for subjective analyses during the first 2 post-operative weeks and will visit the dental clinic at 3, 7, 14 and 60 post-operative days for checkups and clinical examinations.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The aim of the present study is to evaluate the effects of topical cross-linked high molecular weight hyaluronic acid (xHyA) gel on postoperative patient discomfort and wound healing of palatal donor sites after free gingival graft (FGG) surgery.

Twenty patients requiring FGG are randomly assigned into two groups: negative control and a test group receiving xHyA gel in a single application. All surgical interventions are performed by the same surgical team. Anaesthesia of the palatal region is achieved with local infiltrations of mepivacaine 2% with epinephrine 1:100,000. The donor area is delimited by the distal line angle of the canine and the distal line angle of the second molar. A distance ≥ 2 mm from the gingival margin is respected. A half-thickness incision is made and a rectangular FGG with a thickness of ≈1.5 mm and dimensions of ≈20 × 5 mm in length x height respectively is harvested with a 15C scalpel under periodontal probe (PCP-UNC 15, Hu-Friedy Mfg. Co., LLC, Chicago, IL, USA) guidance maintaining a uniform thickness. A 1-minute moderate finger compression with a wet gauze is used to achieve initial haemostasis. Following soft tissue harvesting, in both groups a collagen sponge is placed to protect the palatal donor site, stabilized with cross-mattress sutures. In the test group, xHyA is injected over the exposed connective tissue and into the collagen sponge. In the negative control, the collagen sponge is left dry. In the immediate post-operative period, in order not to disturb the stabilization of the clot and the effects of the topical xHyA, participants are given instructions not to eat, drink, or rinse for about 4 hours. From the day after the surgery, participants are allowed to rinse passively with an ozone-based mouthwash (CollutO3, Innovares S.r.l., Reggio Emilia, Italy) for about 30 seconds twice daily for 2 post-operative weeks. Patients are placed on a soft diet with cold foods for the first week and are advised to avoid any mechanical or thermal trauma. Patients are also instructed not to brush and floss the upper teeth of the sector homolateral to the palatal donor area for one week. Nonsteroidal anti-inflammatory drugs (ibuprofen 600 mg every 6-8 hours up to 3 times a day) to be used as needed are prescribed for pain relief. Palatal sutures are removed after 7 days.

Study Type

Interventional

Enrollment (Actual)

20

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

  • Italy
    • Lombardy
      • Milan, Lombardy, Italy, 20122
        • Implant Center for Edentulism and Jawbone Atrophies, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan

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:

  • Good general health (ASA 1 or 2)
  • No local contraindications to implant surgery procedures (mucosal inflammation, active periodontal disease, erosive mucosal conditions, bone lesions, history of local radiation therapy and bruxism along with inadequate oral hygiene or lack of motivation for home care)
  • Presence of two adjacent implants either submerged or prosthetically loaded
  • Premolar and/or molar sectors of either the mandible or the maxilla
  • Presence of < 2 mm of keratinized mucosa width at the buccal aspect of the said adjacent implants

Exclusion Criteria:

  • Smokers (> 10 cigarettes/day)
  • Subjects with known allergies to penicillin or collagen
  • Poor oral hygiene
  • Uncontrolled systemic pahologies
  • Active periodontal infection
  • No medical history of head and neck radiation therapy
  • No medical history of antiresorptive agents or steroids therapies
  • Pregnant or lactating women
  • Physical or mental disabilities affecting oral hygiene

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: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Test - xHyA
Following palatal soft tissue harvesting, xHyA gel is injected over the exposed palatal connective tissue creating a layer of approximately 1-mm thickness, and a resorbable collagen sponge (CONDRESS®, EURORESEARCH S.r.l., Milan, Italy) soaked with xHyA is adapted and stabilized to the donor area with a 4-0 silk cross mattress suture.
Drug: Test - xHyA
The xHyA gel is contained in a 1.2 mL sterile cartridge containing highly purified 1.6% high molecular weight cross-linked HA and 0.2% natural HA to be injected with a 23G blunt needle. The xHyA gel is applied directly over the exposed connective tissue at the donor area and injected inside a resorbable collagen sponge that is stabilized to the donor site with silk sutures. No further applications of xHyA are planned during the study.
Other Names:
  • xHyA gel
Sham Comparator: Negative control
Following palatal soft tissue harvesting, a dry resorbable collagen sponge (CONDRESS®, EURORESEARCH S.r.l., Milan, Italy) is adapted and stabilized to the palatal donor area with a 4-0 silk cross mattress suture.
Other: Negative control
A dry collagen sponge not loaded with xHyA is adapted and stabilized to the donor area with a 4-0 silk cross mattress suture.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Subjective post-operative morbidity evaluation with a visual analogue scale during the first 2 post-operative weeks
Time Frame: 1, 3, 7 and 14 post-operative days.
The primary outcome of the study is to evaluate the post-operative participants morbidity. Subjective perception of pain, bleeding, burning sensation, discomfort while chewing and stress after free gingival graft harvesting are measured using a numerical rating scale, namely a 10-cm visual analogue scale with extreme endpoints at 0 and 10 marks ("no" and "extreme" respectively) recorded for each variable at one, 3, 7 and 14 post-operative days. The amount of analgesic consumption is also noted by each participant for the purpose of indirect pain measurement via mean consumption of analgesics.
1, 3, 7 and 14 post-operative days.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Landry Wound Healing Index during the first 2 post-operative weeks
Time Frame: 3, 7 and 14 post-operative days
The secondary outcome of the study is the measurement of the palatal wound healing appearance using the Landry Wound Healing Index (LWHI), which has a score range from 1 (very poor) to 5 (excellent) in relation to different healing features including tissue colour, response to palpation, presence of granulation tissue, epithelialization of incision margins and amount of suppuration. The palatal wound healing using the LWHI is graded at 3, 7 and 14 post-operative days by an examiner masked to the type of treatment.
3, 7 and 14 post-operative days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Restitutio ad integrum of the palatal wound with intraoral scans up to 60 post-operative days
Time Frame: 0, 7, 14, and 60 post-operative days
The third outcome is to evaluate the restitutio ad integrum of the palatal wound. To this end, optical intraoral scans of the palatal donor region including the palatal, occlusal and buccal surfaces of the homolateral teeth are acquired with an intraoral scanner (TRIOS 5, 3Shape, Copenaghen, Denmark) before the surgery (baseline scan), and after 7, 14 and 60 days. The .STL files of the scans are imported and overlapped in a digital environment (RealGUIDE®, 3DIEMME, Cantù, Italy) using the teeth surfaces available in all scans as fixed reference points using the best-fit alignment technology. The deepest harvesting point visible in the 7-day post-operative scan, namely the point where the harvested FGG was thicker, is selected as the reference landmark. According to this point, the 7-, 14-, and 60-day post-operative scans are compared to the pre-operative scan in order to assess the differences between the selected landmark and the baseline scan expressed in mm.
0, 7, 14, and 60 post-operative days

Collaborators and Investigators

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

Sponsor

University of Milan

Collaborators

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

September 5, 2022

Primary Completion (Actual)

July 24, 2025

Study Completion (Actual)

October 2, 2025

Study Registration Dates

First Submitted

March 4, 2026

First Submitted That Met QC Criteria

March 4, 2026

First Posted (Actual)

March 9, 2026

Study Record Updates

Last Update Posted (Actual)

March 9, 2026

Last Update Submitted That Met QC Criteria

March 4, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 558_2022bis

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

No individual participant data (IPD) or additional supporting documents will be shared. Data will remain confidential and stored securely at the Implant Center for Edentulism and Jawbone Atrophies, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, in accordance with institutional ethical approval.

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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