Influence of Hyaluronic Acid in the Healing of Palatal Donor Sites During Free Gingival Graft Procedures

NCT07458685 | Completed

• 1 other identifier: 558_2022bis
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Palatal Donor Site Wound Healing; Palatal Wound

Keywords

Free gingival graft; Healing; Hyaluronic acid; Palatal donor site; Palatal healing; Morbidity; Soft tissue harvesting

Outcome Measures

Primary Outcomes (1)

• Subjective post-operative morbidity evaluation with a visual analogue scale during the first 2 post-operative weeks

  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 Outcomes (1)

• Landry Wound Healing Index during the first 2 post-operative weeks

  3, 7 and 14 post-operative days

Other Outcomes (1)

• Restitutio ad integrum of the palatal wound with intraoral scans up to 60 post-operative days

  0, 7, 14, and 60 post-operative days

Study Arms (2)

Test - xHyA

ACTIVE COMPARATOR

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

Negative control

SHAM COMPARATOR

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

Interventions

Test - xHyA DRUG

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.

Also known as: xHyA gel

Test - xHyA

Negative control OTHER

A dry collagen sponge not loaded with xHyA is adapted and stabilized to the donor area with a 4-0 silk cross mattress suture.

Negative control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Milan: lead
• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: collaborator

Study Sites (1)

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

Milan, Lombardy, 20122, Italy

Location

Related Publications (15)

• Ceylan Sen S, Sarac Atagun O, Ustaoglu G, Ozcan E. Comparative evaluation of hyaluronic acid and injectable platelet-rich fibrin in palatal wound healing: a randomized clinical trial. BMC Oral Health. 2025 Oct 29;25(1):1693. doi: 10.1186/s12903-025-07183-9.

  PMID: 41162972 BACKGROUND

• Cankaya ZT, Gurbuz S, Bakirarar B, Kurtis B. Evaluation of the Effect of Hyaluronic Acid Application on the Vascularization of Free Gingival Graft for Both Donor and Recipient Sites with Laser Doppler Flowmetry: A Randomized, Examiner-Blinded, Controlled Clinical Trial. Int J Periodontics Restorative Dent. 2020 Mar/Apr;40(2):233-243. doi: 10.11607/prd.4494.

  PMID: 32032408 BACKGROUND

• Khalil S, Habashneh RA, Alomari S, Alzoubi M. Local application of hyaluronic acid in conjunction with free gingival graft: a randomized clinical trial. Clin Oral Investig. 2022 Feb;26(2):2165-2174. doi: 10.1007/s00784-021-04197-9. Epub 2021 Oct 8.

  PMID: 34623507 BACKGROUND

• Alpan AL, Cin GT. Comparison of hyaluronic acid, hypochlorous acid, and flurbiprofen on postoperative morbidity in palatal donor area: a randomized controlled clinical trial. Clin Oral Investig. 2023 Jun;27(6):2735-2746. doi: 10.1007/s00784-022-04848-5. Epub 2023 Jan 3.

  PMID: 36595064 BACKGROUND

• Yildirim S, Ozener HO, Dogan B, Kuru B. Effect of topically applied hyaluronic acid on pain and palatal epithelial wound healing: An examiner-masked, randomized, controlled clinical trial. J Periodontol. 2018 Jan;89(1):36-45. doi: 10.1902/jop.2017.170105.

  PMID: 28914592 BACKGROUND

• Joshi VM, Kandaswamy E, Germain JS, Schiavo JH, Fm HS. Effect of hyaluronic acid on palatal wound healing: A systematic review. Clin Oral Investig. 2024 Oct 3;28(10):565. doi: 10.1007/s00784-024-05955-1.

  PMID: 39358570 BACKGROUND

• Asparuhova MB, Kiryak D, Eliezer M, Mihov D, Sculean A. Activity of two hyaluronan preparations on primary human oral fibroblasts. J Periodontal Res. 2019 Feb;54(1):33-45. doi: 10.1111/jre.12602. Epub 2018 Sep 27.

  PMID: 30264516 BACKGROUND

• Pilloni A, Shirakata Y, Marini L, Bozic D, Miron RJ, Rotundo R, Stavropoulos A, Sculean A. Hyaluronic acid: A novel approach in regenerative/reconstructive periodontal therapy? Periodontol 2000. 2025 Aug 18. doi: 10.1111/prd.12644. Online ahead of print.

  PMID: 40820678 BACKGROUND

• Valachova K, Hassan ME, Soltes L. Hyaluronan: Sources, Structure, Features and Applications. Molecules. 2024 Feb 5;29(3):739. doi: 10.3390/molecules29030739.

  PMID: 38338483 BACKGROUND

• Aya KL, Stern R. Hyaluronan in wound healing: rediscovering a major player. Wound Repair Regen. 2014 Sep-Oct;22(5):579-93. doi: 10.1111/wrr.12214.

  PMID: 25039417 BACKGROUND

• Li CS, Lee WC, Fu MW, Ying-Shan Su S, Tzeng IS, Fu E. Bioactive materials for post-operative healing and pain relief following palatal epithelialized graft harvesting: A meta-analysis of randomized clinical trials. J Dent Sci. 2025 Apr;20(2):953-961. doi: 10.1016/j.jds.2024.11.013. Epub 2024 Nov 28.

  PMID: 40224047 BACKGROUND

• Leite GG, Viana KSS, Cota LOM, Abreu LG, Esteves Lima RP, Costa FO. Efficacy of different interventions on the morbidity of the palatal donor area after free gingival graft and connective tissue graft: A systematic review. Jpn Dent Sci Rev. 2025 Dec;61:31-40. doi: 10.1016/j.jdsr.2025.03.001. Epub 2025 Mar 12.

  PMID: 40151832 BACKGROUND

• de Almeida MCL, Rocha RGG, Magno MB, Lima RR, Saito MT. Performance of multiple therapeutic approaches for palatal wound healing after soft tissue graft removal - an overview of systematic reviews. Clin Oral Investig. 2024 May 31;28(6):347. doi: 10.1007/s00784-024-05733-z.

  PMID: 38819478 BACKGROUND

• Burkhardt R, Hammerle CH, Lang NP; Research Group on Oral Soft Tissue Biology & Wound Healing. Self-reported pain perception of patients after mucosal graft harvesting in the palatal area. J Clin Periodontol. 2015 Mar;42(3):281-7. doi: 10.1111/jcpe.12357. Epub 2015 Feb 16.

  PMID: 25544993 BACKGROUND

• Tavelli L, Barootchi S, Stefanini M, Zucchelli G, Giannobile WV, Wang HL. Wound healing dynamics, morbidity, and complications of palatal soft-tissue harvesting. Periodontol 2000. 2023 Jun;92(1):90-119. doi: 10.1111/prd.12466. Epub 2022 Dec 30.

  PMID: 36583690 BACKGROUND

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Statistician
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Tenure-Track Researcher

Model Details: Participants are equally distributed to a control and a test group. A simple software-generated random number list with a research randomizer online tool (https://www.randomizer.org/) is used to randomly allocate the participants. In the negative control group, the palatal donor area is left to heal with no topical agent applied; in the xHyA test group, the palatal donor area is treated with xHyA gel topical application.

Study Record Dates

• First Submitted: March 4, 2026
• First Posted: March 9, 2026
• Study Start: September 5, 2022
• Primary Completion: July 24, 2025
• Study Completion: October 2, 2025
• Last Updated: March 9, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)