Study of Hyaluronic Acid Used With Gum Surgery to Treat Gum Recession in Adults

Official title

Effectiveness of Hyaluronic Acid Application in Coronally Advanced Flap Combined With a Subepithelial Connective Tissue Graft Versus Coronally Advanced Flap Combined With a Subepithelial Connective Tissue Graft Alone: A Clinical Trial

Overview

Gingival recession is a common condition in which the gum tissue recedes, exposing the root surface of the tooth. This can lead to tooth sensitivity, higher risk of root decay, and aesthetic concerns. A commonly used surgical treatment is the coronally advanced flap combined with a connective tissue graft (CAF + SCTG), which aims to cover the exposed root and improve gum health. Hyaluronic acid (HA) is a naturally occurring substance in the body that plays an important role in wound healing. It may help improve tissue repair, reduce inflammation, and enhance healing after surgery. This study aims to evaluate whether the use of hyaluronic acid (hyaDENT BG®) in addition to standard surgical treatment improves clinical outcomes in patients with gingival recession. Participants will be randomly assigned to receive either standard treatment alone or standard treatment with hyaluronic acid. The main outcome is the proportion of sites with complete root coverage after 12 months. Additional outcomes include healing, gum tissue improvement, patient-reported pain and discomfort, and aesthetic results. The study also includes a laboratory component to investigate how hyaluronic acid affects cells involved in gum healing.

Detailed description

Gingival recession (GR) is a common mucogingival condition characterized by apical displacement of the gingival margin beyond the cemento-enamel junction, leading to root exposure, dentin hypersensitivity, increased risk of root caries, and aesthetic impairment. The coronally advanced flap combined with a subepithelial connective tissue graft (CAF + SCTG) is considered the gold standard for the treatment of single gingival recession defects, providing predictable root coverage and long-term stability. However, postoperative morbidity, donor-site discomfort, and incomplete root coverage may still occur.

Hyaluronic acid (HA) is a key component of the extracellular matrix with biological properties that promote wound healing, including stimulation of angiogenesis, cell migration, proliferation, and modulation of inflammatory responses. Cross-linked HA formulations exhibit prolonged bioactivity and may enhance soft tissue healing and regeneration in periodontal surgery.

This study is a prospective, randomized, controlled, post-market clinical follow-up (PMCF) trial designed to evaluate the clinical effectiveness and safety of adjunctive cross-linked hyaluronic acid (hyaDENT BG®) in combination with CAF + SCTG for the treatment of single RT1 and RT2 gingival recession defects. A total of 34 patients will be enrolled and randomly allocated in a 1:1 ratio to either the test group (CAF + SCTG with adjunctive HA) or the control group (CAF + SCTG alone). Randomization will be stratified by recession type (RT1 vs RT2), and outcome assessors will be blinded to treatment allocation.

The primary endpoint is complete root coverage (CRC) at 12 months, defined as recession depth equal to 0 mm relative to the cemento-enamel junction. Secondary endpoints include mean root coverage, recession reduction, clinical attachment level gain, probing depth reduction, keratinized tissue gain, early wound healing (Early Wound Healing Score), patient-reported outcomes (pain, discomfort, and oral health-related quality of life), and aesthetic outcomes assessed using the Root Coverage Esthetic Score (RES).

Clinical assessments will be performed at baseline and at predefined follow-up visits up to 12 months post-surgery using standardized protocols and calibrated examiners. Patient-reported outcomes will be collected using validated instruments, including visual analog scales (VAS) and the OHIP-14 questionnaire.

In parallel, an in vitro component will be conducted using primary human gingival fibroblasts isolated from connective tissue grafts obtained during surgery. These cells will be used to evaluate the effects of HA on cell viability, proliferation, migration, gene expression related to wound healing and inflammation, and activation of intracellular signaling pathways.

This combined clinical and translational approach aims to provide comprehensive evidence on both the clinical performance and biological mechanisms of action of hyaluronic acid in periodontal plastic surgery.

Interventions

• Procedure Coronally Advanced Flap with Connective Tissue Graft
  Standard periodontal plastic surgery procedure for root coverage involving coronally advanced flap (CAF) combined with a subepithelial connective tissue graft (SCTG). The technique aims to cover exposed root surfaces and improve soft tissue thickness and stability.
• Device Cross-linked Hyaluronic Acid Gel
  Application of cross-linked hyaluronic acid gel (hyaDENT BG®) as an adjunct to periodontal surgery. The gel is applied to the recipient site and used to immerse the connective tissue graft prior to placement, aiming to enhance soft tissue healing, promote cell proliferation and angiogenesis, and improve clinical outcomes.

Primary outcome measures

• Complete Root Coverage (CRC) [Time frame: 12 months]

Secondary outcome measures (10)

• Mean Root Coverage (MRC) [Time frame: 12 months]
• Recession Reduction (RecRed) [Time frame: 12 months]
• Clinical Attachment Level (CAL) Gain [Time frame: 12 months]
• Probing Depth (PD) Reduction [Time frame: 12 months]
• Keratinized Tissue Width (KT) Gain [Time frame: 12 months]
• Early Wound Healing Score (EHS) [Time frame: 3 days, 14 days, and 6 weeks]
• Postoperative Pain and Discomfort (VAS) [Time frame: 3 days, 14 days, and 6 weeks]
• Oral Health-Related Quality of Life (OHIP-14) [Time frame: 3 days, 14 days, and 6 weeks]
• Root Coverage Esthetic Score (RES) [Time frame: 12 months]
• Surgical and Postoperative Complications [Time frame: up to 12 months]

Eligibility criteria

Inclusion criteria

• \- Age ≥ 18 years, in good general health (ASA I or II)
• Presence of a single gingival recession defect classified as RT1 or RT2
• Recession depth ≥ 2 mm with identifiable cemento-enamel junction (CEJ)
• Presence of at least 1 mm of keratinized tissue at the defect site
• No active periodontal disease (probing depth ≤ 4 mm and no bleeding on probing at the selected tooth)
• Full-Mouth Plaque Score (FMPS ≤ 20%) and Full-Mouth Bleeding Score (FMBS ≤ 20%)
• Vital tooth without caries, cervical lesions, or defective restorations
• Good oral hygiene and motivation to maintain plaque control
• Ability and willingness to comply with study procedures
• Signed informed consent

Exclusion criteria

• Uncontrolled systemic diseases (e.g., uncontrolled diabetes, severe cardiovascular disease, immunodeficiency)
• Pregnant or breastfeeding women
• Autoimmune diseases or immunosuppressive therapy
• Known hypersensitivity to hyaluronic acid
• Heavy smokers (>10 cigarettes/day) or recent tobacco use
• Active periodontal disease at the study site
• Caries, root fractures, endodontic lesions, or defective restorations at the study tooth
• Previous mucogingival surgery at the study site
• Recent use of antibiotics, corticosteroids, or anti-inflammatory drugs
• Coagulation disorders or anticoagulant therapy contraindicating surgery
• Hormonal disorders affecting wound healing
• Acute oral infections
• Any condition that may interfere with study participation or follow-up

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Portugal · 1 center

• CEPI - Clinical Center for Periodontology and Implantology — Porto

Publications

• Guldener K, Lanzrein C, Eliezer M, Katsaros C, Stahli A, Sculean A. Treatment of single mandibular recessions with the modified coronally advanced tunnel or laterally closed tunnel, hyaluronic acid, and subepithelial connective tissue graft: a report of 12 cases. Quintessence Int. 2020;51(6):456-463. doi: 10.3290/j.qi.a44492. PMID 32368762
• 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
• Pilloni A, Schmidlin PR, Sahrmann P, Sculean A, Rojas MA. Effectiveness of adjunctive hyaluronic acid application in coronally advanced flap in Miller class I single gingival recession sites: a randomized controlled clinical trial. Clin Oral Investig. 2019 Mar;23(3):1133-1141. doi: 10.1007/s00784-018-2537-4. Epub 2018 Jun 30. PMID 29961138

Identifiers

NCT: NCT07529340 · 24/2023

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗