Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico | OTHER |
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Landry Wound Healing Index during the first 2 post-operative weeks | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Restitutio ad integrum of the palatal wound with intraoral scans up to 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. |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Implant Center for Edentulism and Jawbone Atrophies, Fondazione IRCCS CÃ Granda Ospedale Maggiore Policlinico, University of Milan | Milan | Lombardy | 20122 | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41162972 | Background | 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. | |
| 32032408 | 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. |
Not provided
Not provided
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 CÃ Granda Ospedale Maggiore Policlinico, in accordance with institutional ethical approval.
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Statistician
|
|
| 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. |
|
| 3, 7 and 14 post-operative days |
| 0, 7, 14, and 60 post-operative days |
| 34623507 | 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. |
| 36595064 | 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. |
| 28914592 | 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. |
| 39358570 | 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. |
| 30264516 | 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. |
| 40820678 | 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. |
| 38338483 | Background | Valachova K, Hassan ME, Soltes L. Hyaluronan: Sources, Structure, Features and Applications. Molecules. 2024 Feb 5;29(3):739. doi: 10.3390/molecules29030739. |
| 25039417 | 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. |
| 40224047 | 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. |
| 40151832 | 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. |
| 38819478 | 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. |
| 25544993 | 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. |
| 36583690 | 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. |