The Clinical and Biological Effects of Leucocyte and Platelet-rich Fibrin (L-PRF) on Post-extraction Sockets Healing

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 post-extraction sockets healing.

Detailed Description
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Tooth extraction is one of the most frequent dental surgical procedures. Following tooth extraction, dimensional changes of the alveolus are inevitable, which consequently decrease the height and width of alveolar bone and impair ideal implant placement and conventional prosthetic treatment. In order to reduce the bone resorption after tooth extraction, the use of platelet concentrates has been proposed. Platelet rich fibrin (PRF) is a second generation of platelet concentrates consisting of platelets, leukocyte and growth factors harvested from blood. PRF not only supports hemostasis but also favors the natural wound healing process. Over the past decade, PRF has gained tremendous momentum having been utilized for a variety of dental and medical procedures including the management of post-extraction sockets. To date, several studies have assessed the efficacy of the use of PRF in promoting postextraction sockets healing. However, results remain contradictory and mainly focus on the clinical and radiological hard and soft tissue healing, aesthetics and postoperative discomfort. The mechanistic hypothesis is that growth factors released by PRF preparations modulate the wound healing process but the effect of local PRF application on the kinetics of release of wound healing modulators has not been studied so far. There is also a lack of information in the literature regarding the biological evaluation during postextraction sockets healing to understand the potential mechanisms. In order to assess the presence or follow dynamics of biomarkers, in this study wound fluid (WF) will be collected from the post-extraction sockets and utilized for multiplex immunoassay. Multiplex immunoassay allows simultaneous quantification of multiple markers providing unique information for a more complete understanding of the potential mechanism of PRF and spontaneous extraction socket healing. Therefore, the aim of this randomized clinical trial is to evaluate the effects of PRF on biomarkers response during post-extraction sockets healing.

Official Title
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The Clinical and Biological Effects of Leucocyte and Platelet-rich Fibrin (L-PRF) on Post-extraction Sockets Healing: a Randomized Controlled Trial

Conditions
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Tooth Extraction

Intervention / Treatment
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* Other: leucocyte and platelet-rich fibrin (L-PRF)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is willing and able to give informed consent for participation in the study Healthy males and females of age 18-70 Need for two or more extractions of single rooted teeth in the presence of adjacent teeth or implants due to unrestorable caries, residual roots, root fractures or orthodontic treatment Able (in the investigators opinion) and willing to comply with all study requirements Interested in tooth replacement with dental implants Exclusion Criteria: Endodontic periapical lesions with a diameter of more than 5 mm (radiographically determined) Sites with buccal and lingual bone plate loss more than 5 mm Frank purulence or acute abscess at the time of extraction Pregnancy or lactation Smokers or alcoholics Platelet dysfunction syndrome or thrombocytopenia Uncontrolled diabetes Medical contraindications to elective oral surgery procedures

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: Basic Science
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<br>Post-extraction sockets will be filled with autologous leucocyte and platelet-rich fibrin (L-PRF) clot. | Other: leucocyte and platelet-rich fibrin (L-PRF)<br>* The blood collected from each patient will be centrifuged immediately at 2700 rpm for 12 min to separate L-PRF.<br>|
| No Intervention: Control<br>Post-extraction sockets will be left to heal spontaneously with natural blood clot. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentrations changes of the molecules and inflammatory mediators | Concentrations changes of the molecules and inflammatory mediators in the gingival crevicular fluid (GCF) or wound fluid (WF) from the extraction sockets in L-PRF group and control group at baseline (from GCF), 6 hours, 24 hours, 3 days, 7 days. | Baseline, 6 hours, 24 hours, 3 days and 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genes expression profiles | Genes expression profiles of the growth and differentiation factors and inflammatory mediators from the tissue specimen taken from the post-extraction sockets at 3 days. | Baseline and 3 days | 
| Laser Doppler Flowmetry (LDF) measurement | A commercially available Laser Doppler Blood FlowMeter equipped with a standard fiber optic probe will be used for LDF measurements before tooth extraction, immediately postoperatively, 6 hours, 24 hours, 3 days and 7 days. | Before and immediately after the tooth extraction, 6 hours, 24 hours, 3 days and 7 days | 
| Radiographic bone changes (Cone-beam computed tomography) | Cone-beam computed tomography (CBCT) images will be obtained before extraction as the baseline and at the 4 months. | Baseline and 4 months | 
| Wound Healing Index (HI) | Soft tissue healing will be assessed by Wound Healing Index (1 = very poor, 2 = poor, 3 = good, 4 = very good, 5 = excellent). | 6 hours, 24 hours, 3 days and 7 days | 
| Visual analog scale (VAS) | A 10-point VAS with a score of 0 that equals no pain and a score of 10 that equals worst pain imaginable will be used to evaluate the postoperative pain at 6 hours, 24 hours, 3 days and 7 days. The patients will be asked to fill the pain they feel at the time of questioning. Questionnaires will be collected at the one-week follow-up visit. | 6 hours, 24 hours, 3 days and 7 days |