Mechanisms of LPRF Action in the Promotion of Wound Healing and Tissue Regeneration

Study Overview
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Brief Summary
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This study evaluates the clinical and biological effects of leucocyte and platelet-rich fibrin (L-PRF) on intraoral wound healing.

Detailed Description
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Gingival recession is characterized by the exposure of root surfaces of the tooth, is attributed to the apical migration of the gingival marginal tissue, and it is a frequently noted clinical feature in all populations. Other than cosmetic problems, a gingival recession can have a causative role in tooth sensitivity, and contribute to difficulties in oral hygiene maintenance or root caries. Moreover, it may worsen with time. The ultimate goal of surgical root-coverage procedures (Periodontal plastic surgery) is the elimination of the recession defect with minimal probing depths after treatment, along with the ability to restore the natural color and texture of the gingiva (gum). By achieving root coverage, overall improved aesthetics, prevention of non-carious cervical lesions or root caries, and treatment of the resulting root sensitivity should be expected. Surgical interventions in general, and in particular those aiming to reconstruct tissues lost due to trauma or disease in particular, are biologically dependent on a cascade of unimpaired wound healing mechanisms, including a non-disrupted inflammatory process, vascularization(blood supply) of the wound area, and consequent tissue regeneration. Wound healing has been defined as the natural response to injury compiling a cascade of complex events orchestrated in a way that many cell types guided by the release of soluble mediators and signals. In a bid to enhance this phase, autologous platelet 'concentrates' were developed, derived from centrifuged blood of patients and applied as surgical adjuncts. Previous studies indicate that leucocyte plasma rich fibrin (LPRF/newest generation of platelet concentrates) preparations significantly modulate wound healing and promote tissue regeneration in a variety of oral surgical procedures. Clinical studies where LPRF is analyzed at the molecular level to quantify the temporal release of growth factors, cytokines, or other biomolecular components are still lacking. Despite the broad application of LPRF in modern dentistry information which integrates clinical and molecular data from in vivo models are essential to elucidate its relevant biological mechanisms. The mechanisms of action are unclear, and the relative role of their different components have not been fully explained. This study will aim to investigate if LPRF can offer superior clinical outcomes and will compare the concentrations and kinetics of wound healing regulators in root coverage procedures with and without local application of LPRF.

Official Title
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Mechanisms of LPRF Action in the Promotion of Wound Healing and Tissue Regeneration: A Randomised Controlled Trial

Conditions
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Gingival Recession

Intervention / Treatment
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* Procedure: leucocyte and platelet-rich fibrin (L-PRF) in combination with CAF
* Procedure: CAF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-70 Non-smokers or former smokers Participants must agree to read the Patient information leaflet and provide a signed a copy of the Informed Consent, after the study design has been completely explained. Presence of bilateral isolated Miller Class I and II gingival recessions in anterior and premolar regions. Presence of minimum 2 mm of keratinized gingiva apical to the gingival margin at the selected sites. Exclusion Criteria: The patient is medically compromised with history of diabetes mellitus or hepatic or renal disease, or other serious medical conditions or transmittable diseases e.g. Hepatitis B or C or AIDS. History of rheumatic fever, heart murmur, mitral valve prolapse, artificial heart valve or conditions which would require antibiotic prophylaxis invasive dental procedures. Patients undergoing therapies involving the use of antibiotic, anti-inflammatory or anticoagulant drugs during the month prior to the baseline exam. History of alcohol use or drug abuse. Self-reported pregnancy or lactation. Subjects would be considered inappropriate for the trial if they have a history of pre-existing acute or chronic medical or psychiatric illness and laboratory abnormality which may pose to increase the risk of the subjects involved in the trial or administering the investigational product or may interfere with the interpretation of trial results.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Split-mouth design allowing to assess two types of treatment in the same patient.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: L-PRF membrane<br>Periodontal plastic surgical procedures (coronally advanced flap, CAF) in combination with a double layer autologous leucocyte and platelet-rich fibrin (L-PRF) membrane. | Procedure: leucocyte and platelet-rich fibrin (L-PRF) in combination with CAF<br>* Completing root coverage by coronally advanced flap technique in combination with L-PRF.<br>|
| Active Comparator: Control<br>CAF | Procedure: CAF<br>* Completing root coverage by coronally advanced flap technique alone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of gingival recession depth (GR) from baseline to 6 months | Measured from the CEJ to the apical extension of the gingival margin in mm with the use of Florida probe. | Baseline, 3 months, and 6 months | 
| Change of probing pocket depth (PPD) from baseline to 6 months | Measured from the gingival margin to base of the gingival sulcus in mm with the use of Florida probe. | Baseline, 3 months, and 6 months | 
| Change of clinical attachment level (CAL) from baseline to 6 months | Measured from cementoenamel junction (CEJ) to the base of the gingival sulcus in mm with the use of Florida probe. | Baseline, 3 months, and 6 months | 
| Change of keratinized mucosa width (KMW) from baseline to 6 months | Measured from the gingival margin to the mucogingival line in mm with the use of Florida probe. | Baseline, 3 months, and 6 months | 
| Change of thickness of keratinised gingiva (GT) from baseline to 6 months | Measured 3 mm apical to the gingival margin in mm measured by superimposition of intraoral digital scanning images. | Baseline, 3 months, and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of gingival wound fluid molecules | Concentration changes of the molecules and inflammatory mediators in the wound fluid (WF). | Baseline, 6 hours, 3 days, and 7 days |