Clinical Evaluation of Hyaluronic Acid and Platelet Rich Fibrin Injection Efficacy in Interdental Papilla Reconstruction

The goal of this clinical trial is to evaluate and compare the efficacy of injectable platelet rich fibrin (i-PRF) and hyaluronic acid (HA) in reconstruction of interdental papilla loss. The main questions it aims to answer are:

• How compareable are above mentioned two interventions (i-PRF&HA) in reconstruction of interdental papilla loss?
• Which treatment option is better accepted by patients? Which treatment option would patients be more satisfied with? Participants with multiple interdental papilla loss will be treated with both i-PRF and HA in split-mouth design. Researchers will compare two treatment options to see if black triangles caused by interdental papilla loss closes and if yes, for how long do they last.

Study Overview

• Status: Completed
• Conditions: Interdental Papilla Loss
• Intervention / Treatment: Biological: I-PRF Injection; Drug: Teosyal PureSense Global Action HA Injection

Detailed Description

Nowadays, individuals give great importance to their appearance and dental aesthetics plays a key role in their personal appearance. Dental aesthetics is a combination of white and pink aesthetics formed by teeth and gums. The part of the gingival tissue that fills the triangular shaped spaces between the teeth is the interdental papilla. The presence of papillae in the teeth is closely related to the distance between the contact point between the teeth and the alveolar bone crest. Periodontal diseases, traumatic oral hygiene practices, incorrect orthodontic forces, incompatible restoration contour, the presence of diastema as a result of neighbouring teeth not being in contact, and tooth loss can cause loss of interdental papillae, resulting in the formation of gaps called black triangles. In addition to aesthetic problems, loss of interdental papillae can cause speech difficulties and food impaction.

Interdental papilla loss is one of the most important aesthetic periodontal difficulties and at the same time one of the most difficult problems to treat. Various surgical methods and flap designs have been proposed for the treatment and reconstruction of interdental papillae. However, current surgical methods have limited success and lack predictability, especially because the gingival papilla has a sensitive structure and less blood supply compared to other parts of the gingiva. Therefore, non-surgical methods have gained importance. As a result of the development of tissue engineering, dermal filling materials have started to be produced in recent years. Among these materials, hyaluronic acid (HA) is one of the basic components of connective tissue and especially its water binding/retention property makes it a determinant of tissue volume. HA enables the migration of fibroblast cells involved in collagen production and also acts as a liquid matrix where collagen and elastic fibres will proliferate. Due to these properties, Becker et al. first demonstrated in 2010 that it was possible to reconstruct a small area of interdental papilla loss in a minimally invasive and predictable manner using injectable HA gel. Subsequently, HA injections in interdental papil reconstructions have frequently been successfully reported in the literature.

Platelet Rich Fibrin (PRF) is an autologous, membrane-form product prepared by centrifugation of the patient's own blood. This fibrin matrix containing platelets, leukocytes and various growth factors is used especially in regenerative periodontal surgical operations. Injectable PRF (i-PRF), obtained by modifying the preparation protocol, forms a dynamic hydrogel by increasing the number of cells and releasing growth factors more frequently. I-PRF serves as a source of slow-release growth factors that help remodelling of the interdental papilla. Using data obtained through standardised photographs, the project will evaluate the effectiveness of area closure rates of black triangles caused by papilla loss over a 3-month period and measure patient feedback and satisfaction.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 4

Contacts and Locations

Study Locations

• Turkey (Türkiye)
  • Istanbul, Turkey (Türkiye)
    • Altinbas University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Systemically healthy (without cardiovascular diseases, diabetes, thyroid diseases, auto-immune diseases)
• Patients with PPI 2 and PPI 3 papillae according to the Papillary Presence Index classification
• Probable pocket depth of 4 mm or less in the relevant area
• Plaque index and gingival index in the range of 0-1
• Neighbouring teeth in contact with each other in the relevant area
• Absence of any restoration in the relevant area
• Non-smoker
• No surgical periodontal treatment in the last 6 months
• For female subjects not pregnant or lactating
• No known allergy to hyaluronic acid

Exclusion Criteria:

• Not systemically healthy (with cardiovascular diseases, diabetes, thyroid diseases, auto-immune diseases)
• Diagnosed with periodontitis
• History of allergic reactions to hyaluronic acid
• Less than 2 mm keratinized tissue height in the relevant area
• Teeth crowding in relevant area
• Any kind of restoration (fillings, crowns, etc.) in the relevant area
• Smoker
• Ongoing orthodontic treatment
• Having parafunctional habits (bruxism, etc.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Injectable PRF; i-PRF is produced by cenrifugation of patients own blood. Injection of 0.1-0.2 ml per interdental papilla 3 times with 3-week interval.	Biological: I-PRF Injection; İnterdental papilla will be injected by i-PRF.; Drug: Teosyal PureSense Global Action HA Injection; Interdental papilla will be injected by Teosyal PureSense Global Action HA gel.
Active Comparator: Hyaluronic Acid; Teosyal® Global Action PureSense. Composition: Cross-linked hyaluronic acid (HA): 25 mg/ml Lidocaine; 0,3%, (injection). Injection of 0.1-0.2 ml per interdental papilla 3 times with 3-week interval.	Biological: I-PRF Injection; İnterdental papilla will be injected by i-PRF.; Drug: Teosyal PureSense Global Action HA Injection; Interdental papilla will be injected by Teosyal PureSense Global Action HA gel.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Black Triangle Area	Using standardized intraoral photographs, change in black triangle area in mm² will be measured	After the last injection: 1 month - 3 months
Intedental Papilla Reconstruction Rate	Changes in Black Triangle Area given in percentage to the baseline values	After the last injection: 1 month - 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Satisfaction Score	Patient satisfaction of each treatment option will be measured using Visual Analog Score (VAS).	After the last injection: 3 months
Black Triangle Width	Using standardized intraoral photographs, change in black triangle width in mm will be measured	After the last injection: 1 month - 3 months
Black Triangle Height	Using standardized intraoral photographs, change in black triangle height in mm will be measured	After the last injection: 1 month - 3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between Interdental Papilla Reconstruction Rate and Interdental Bone Crest-Interproximal Contact Point Distance	Correlation between Interdental Papilla Reconstruction Rate(%) and Interdental Bone Crest-Interproximal Contact Point Distance(mm)	After the last Injection: 1 month-3 months
Correlation between Interdental Papilla Reconstruction Rate and Keratinised Tissue Thickness	Correlation between Interdental Papilla Reconstruction Rate(%) and Keratinised Tissue Thickness(mm)	After the last Injection: 1 month-3 months

Collaborators and Investigators

• Sponsor: Altinbas University

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2024
• Primary Completion (Actual): June 1, 2025
• Study Completion (Actual): June 25, 2025

Study Registration Dates

• First Submitted: March 11, 2024
• First Submitted That Met QC Criteria: March 11, 2024
• First Posted (Actual): March 18, 2024

Study Record Updates

• Last Update Posted (Actual): December 8, 2025
• Last Update Submitted That Met QC Criteria: December 1, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: hyaluronic acid; interdental papilla reconstruction; black triangle; injectable platelet rich fibrin; interdental papilla loss
• Additional Relevant MeSH Terms: Therapeutics; Drug Administration Routes; Drug Therapy; Injections
• Other Study ID Numbers: 2023/218

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No