Clinical and Histological Evaluation of Subepithelial Connective Tissue Graft Maturation at Different Healing Timepoints, With and Without Topical Application of a Polynucleotide- and Hyaluronic Acid-Based Gel

NCT07708051 | Not Yet Recruiting

• 1 other identifier: 95625625.9.0000.5419
• Study Type: interventional
• Target: 15
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study evaluates whether a 9-week healing interval is sufficient for subepithelial connective tissue graft (SCTG) maturation after palatal harvesting, and whether topical application of a polynucleotide and hyaluronic acid gel (Regenfast®) improves tissue quality. This is a randomized, blinded, controlled clinical trial with a split-mouth design involving 15 participants. Each participant undergoes bilateral SCTG harvesting from the palate in two surgical sessions 9 weeks apart. In the first session, one randomized side receives a single topical application of Regenfast® after graft removal; the contralateral side serves as control. Standardized tissue fragments (3×3 mm, 1.5 mm thickness) are collected from each graft for histological (HE, Picrosirius Red) and immunohistochemical analyses. Comparisons are made between grafts collected at baseline and after 9 weeks, and between sides treated with or without the gel.

Conditions

Gingival Recession, Generalized; Gingival Recession, Localized; Wound Healing; Palate; Wound

Keywords

Subepithelial connective tissue graft; Palatal donor site; Wound healing; Gingival Recession; Hyaluronic acid; Polynucleotides; Split-mouth clinical trial; Histological analysis

Outcome Measures

Primary Outcomes (3)

• Histological Tissue Architecture of the Subepithelial Connective Tissue Graft

  Morphological evaluation of tissue architecture using hematoxylin-eosin (HE) staining, assessing cellular organization, connective tissue maturation, and overall structural quality of grafts harvested at baseline and 9 weeks after initial harvesting, with and without topical application of polynucleotide and hyaluronic acid gel (Regenfast®).

  Baseline and 9 weeks after initial graft harvesting

• Collagen Density and Fiber Maturation of the Subepithelial Connective Tissue Graft

  Quantification of collagen density and proportion of type I and type III collagen fibers using Picrosirius Red staining under polarized light microscopy, comparing grafts harvested at baseline and 9 weeks after initial harvesting, with and without topical application of polynucleotide and hyaluronic acid gel (Regenfast®).

  Baseline and 9 weeks after initial graft harvesting

• Microvascular Density and Vascular Area of the Subepithelial Connective Tissue Graft

  Immunohistochemical evaluation of vascularization, assessing microvessel density (number/mm²) and vascular area (%) of grafts harvested at baseline and 9 weeks after initial harvesting, with and without topical application of polynucleotide and hyaluronic acid gel (Regenfast®).

  Baseline and 9 weeks after initial graft harvesting

Study Arms (2)

Regenfast Gel Application Test Side

EXPERIMENTAL

Palatal side randomized to receive a single topical application of polynucleotide and hyaluronic acid gel (Regenfast, 0.3 ml) immediately after subepithelial connective tissue graft (SCTG) harvesting in the first surgical session. The contralateral side receives no intervention. SCTG is harvested again from the same site after 9 weeks for histological and immunohistochemical analyses.

Drug: polynucleotide and hyaluronic acid gel; Procedure: subepithelial connective tissue graft harvesting

No Intervention - Control Side

ACTIVE COMPARATOR

Contralateral palatal side receiving no topical intervention after SCTG harvesting in the first surgical session. SCTG is harvested again from the same site after 9 weeks. This arm serves as control for both the healing time comparison (baseline vs 9 weeks) and the biomaterial effect comparison.

Procedure: subepithelial connective tissue graft harvesting

Interventions

polynucleotide and hyaluronic acid gel DRUG

Single topical application of polynucleotide and hyaluronic acid gel (Regenfast, 0.3 ml) to the palatal donor site immediately after subepithelial connective tissue graft harvesting in the first surgical session, before suturing.

Regenfast Gel Application Test Side

subepithelial connective tissue graft harvesting PROCEDURE

Bilateral subepithelial connective tissue graft harvesting from the palatal donor site using the double incision technique (Harris, 2003) with a standardized 1.5 mm guide scalpel, under local anesthesia (2% lidocaine with 1:100,000 epinephrine). Performed in two surgical sessions with a 9-week interval.

No Intervention - Control Side; Regenfast Gel Application Test Side

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age between 18 and 60 years
• Good general systemic health
• Presence of multiple bilateral gingival recessions with indication for root coverage

You may not qualify if:

• Smoking of any intensity
• Pregnancy or lactation
• Oral lesions or alterations in the palatal mucosa
• Previous history of graft harvesting from the donor area
• Continuous use of medications that interfere with the inflammatory response, such as corticosteroids or immunosuppressants
• Autoimmune diseases, coagulation disorders, or other systemic conditions affecting wound healing

Sponsors & Collaborators

• University of Sao Paulo: lead
• Instituto Kahn Odontologia: collaborator

Related Publications (8)

• Harris RJ. Histologic evaluation of connective tissue grafts in humans. Int J Periodontics Restorative Dent. 2003 Dec;23(6):575-83.

  PMID: 14703761 BACKGROUND

• Harris RJ. The connective tissue and partial thickness double pedicle graft: a predictable method of obtaining root coverage. J Periodontol. 1992 May;63(5):477-86. doi: 10.1902/jop.1992.63.5.477.

  PMID: 1527693 BACKGROUND

• Cairo F, Cavalcanti R, Barbato L, Nieri M, Castelluzzo W, di Martino M, Pilloni A. Polynucleotides and Hyaluronic Acid (PN-HA) Mixture With or Without Deproteinized Bovine Bone Mineral as a Novel Approach for the Treatment of Deep Infrabony Defects: A Retrospective Case Series. Int J Periodontics Restorative Dent. 2025 Mar 6;45(2):153-163. doi: 10.11607/prd.7065.

  PMID: 38363180 BACKGROUND

• Pilloni A, Rojas MA, Trezza C, Carere M, De Filippis A, Marsala RL, Marini L. Clinical effects of the adjunctive use of polynucleotide and hyaluronic acid-based gel in the subgingival re-instrumentation of residual periodontal pockets: A randomized, split-mouth clinical trial. J Periodontol. 2023 Mar;94(3):354-363. doi: 10.1002/JPER.22-0225. Epub 2022 Nov 23.

  PMID: 36189651 BACKGROUND

• Skierska I, Gorski B, Fus L. Tunnel technique and subepithelial connective tissue graft, with or without cross-linked hyaluronic acid, in the treatment of multiple gingival recessions: 12-month outcomes of a randomized clinical trial. J Periodontol. 2024 Nov;95(11):1060-1072. doi: 10.1002/JPER.24-0093. Epub 2024 May 29.

  PMID: 38808976 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

• Tavelli L, Barootchi S, Siqueira R, Kauffmann F, Majzoub J, Stefanini M, Zucchelli G, Wang HL. Three-Dimensional Volumetric Analysis of the Palatal Donor Site Following Soft Tissue Harvesting. Int J Periodontics Restorative Dent. 2022 May-Jun;42(3):393-399. doi: 10.11607/prd.5268.

  PMID: 35472117 BACKGROUND

• Soileau KM, Brannon RB. A histologic evaluation of various stages of palatal healing following subepithelial connective tissue grafting procedures: a comparison of eight cases. J Periodontol. 2006 Jul;77(7):1267-73. doi: 10.1902/jop.2006.050129.

  PMID: 16805692 BACKGROUND

MeSH Terms

Conditions

Gingival Recession; Wounds and Injuries

Interventions

Polynucleotides

Condition Hierarchy (Ancestors)

Gingival Diseases; Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases; Periodontal Atrophy

Intervention Hierarchy (Ancestors)

Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Marcella B Kahn, DDS, MS Candidate

  Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo (FORP-USP)

  PRINCIPAL INVESTIGATOR

• Michel Reis Messora, DDS, MS, PhD

  Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo (FORP-USP) Role: Study Chair

  STUDY CHAIR

• Sergio Kahn, DDS, MS, PhD

  Instituto Kahn Odontologia, Rio de Janeiro

  STUDY DIRECTOR

Central Study Contacts

Marcella Kahn, DDS, MS Candidate

CONTACT

+5521988483846; mbkahn@usp.br

Michel Reis Messora, DDS, MS, PhD

CONTACT

m.messora@forp.usp.br

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Participant and care provider (surgeon performing graft collection) are blinded to side allocation. Outcomes assessors performing histological and immunohistochemical analyses are blinded throughout the study. The investigator responsible for topical application of Regenfast® is not blinded, as they must apply the gel to the assigned side immediately after graft removal.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MSc Student, Periodontics Postgraduate Program

Model Details: Split-mouth design in which each participant contributes two simultaneous treatment sites (left and right palate). One randomized side receives a single topical application of Regenfast® (polynucleotide and hyaluronic acid gel) after the first SCTG harvest; the contralateral side receives no intervention and serves as control. Both sides are harvested again after 9 weeks, allowing paired intraindividual comparisons.

Study Record Dates

• First Submitted: July 1, 2026
• First Posted: July 16, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): February 27, 2027
• Last Updated: July 16, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share